challenges in developing biomarker assays for patient ......drugs –clinical and regulatory...

第23回『第一三共セミナー』バイオマーカーによる創薬と医薬品開発の変革

バイオマーカー推進部村上雅人2019年2月20日

プレゼンター紹介

• 村上雅人 MD, PhD, MBA • 臨床病理、アカデミアでの分子研究日米欧企業におけるトランスレーショナル・メディスン、創薬、開発経験

• 2017 第一三共㈱バイオマーカー推進部長• 2016 第一三共㈱入社Exe Medical Director

Oncology Function• 2010 ノバルティス社 Oncology Basel Switzerland

Head Mol Pathology• 2007 イタリア、ミラノ

Institute of Molecular Oncology Foundation • 2000 東京大学医学部大学院• 1998 東海大学医学部卒

2

本日のアジェンダ

u バイオマーカーとバイオマーカーによる医薬品開発

u バイオマーカーアッセイ、コンパニオン診断薬（CDx）の開発

u DSパイプラインにおけるバイオマーカー

3

バイオマーカーの定義BEST effortsFDA-NIHバイオマーカーワーキンググループの結果、「バイオマーカー」という用語の定義がどのように進化したかの例を以下に示す：l バイオマーカーの初期定義：正常な生物学的プロセス、病原性プロセス、または治療

的介入に対する薬理学的反応の指標として客観的に測定および評価される特性。l バイオマーカーのBEST定義：正常な生物学的プロセス、病原性プロセス、または治

療的介入を含む曝露もしくは介入に対する反応の指標として測定される、定義された特性。分子的、組織学的、X線学的、または生理学的特徴は、バイオマーカーのタイプである。バイオマーカーは、患者さんがどのように感じ、機能し、生存するかを評価するものではない。

NIHとFDAは、バイオマーカーとエンドポイントについて話す際に、誰もが同じ言葉で話せるように、ステークホルダーがBEST用語と定義を使うことを奨励する。

U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES/U.S. FOOD & DRUG ADMINISTRATION JUNE 2016より

4

「バイオマーカー」とは何か? 定義とタイプ

カテゴリー• 診断マーカー(疾患バイオマーカー)ー病原性表現型の(ノンレスポンダー/レスポンダー)、

標的関与(分子標的)を測定

• 安全性/毒性バイオマーカーー毒性/有害事象の早期指標

• PK/PDバイオマーカーー生体に対する薬物の影響（PK）および薬物に対する生体の反応（PD）を測定

• 疾患進行度バイオマーカー(代理エンドポイント)ーアウトカムに関する臨床上の決断を促進

• 効果予測バイオマーカーー患者グループを層別化

• 予後マーカーなど

測定の対象は?• 核酸(DNA、mRNA)

• タンパク質、ペプチド

• 画像診断(CT、MRI、PETなど)

• 生化学検査5

臨床における現在のバイオマーカーの例

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http://www.rek.or.jp/personal/result/result02

https://www.roche-td.jp/products/reagent/ihc/pages/her2.html

http://jtd.amegroups.com/article/view/12725/html

cobas® EGFR Mutation Test v2 (US-IVD)

https://molecular.roche.com/

目的に合わせて開発・使用間違いは許されない

なぜバイオマーカーが重要であるのか?

医薬品開発に向けて

• 正しい適応症・正しい患者の把握適応症の選択;患者選択/層別化するCDxの開発

• 医薬品の薬効の確認標的関与、薬力学、代理（サロゲート）エンドポイント

• 医薬品の生物学的作用の理解作用メカニズム、耐性獲得メカニズム併用の根拠、次世代医薬品

Dana Olsen and JanTrøst Jørgensen. Companion diagnostics for targeted cancer drugs – clinical and regulatory aspects. Frontiers in Oncology | Pharmacology of Anti-Cancer Drugs. May 2014 Volume 4 Article 105.

CDxを用いた臨床試験では、成功確率が大幅に上昇

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バイオマーカーは臨床試験で有用か?

バイオマーカー無しの試験バイオマーカー有りの試験標的への関与が不明標的へ関与したのかがわかる薬物がMOAに従って作用したかどうか理解できない

MOA PDレスポンスが観察できる

薬物反応が不明 PK/PDパラメータが定義できる用量の選択/予測が不能用量が選択できる疾患を記述的にしか分類できない疾患を分子的に分類できる経験則的な医薬品開発となるバイオマーカーによる医薬品開発が可能患者の選択ができない患者選択が可能POCは一般的に後期開発まで不明 POCの早期実証の可能性がある

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バイオマーカーによる試験デザインが臨床開発を加速

並行開発モデル

順次開発モデル

前臨床 Ph1 Ph2

前臨床 Ph1

Ph2

Ph3

5-10 年

2.5-3 年

1.5-2 年

1-1.5 年

Ph3 TR

現在のプロセス

Cancer Enterpriseにおける開発

上市

申請

BM, PDX

ß 患者ニーズを明確化ß 選択された患者によるP1試験、P2試験結果でのNDA提出ß シンプルなプロセスと迅速な意思決定ß 創薬、開発、CMC、マーケティング、事業開発との早期からの協働

最近の例ß オシメルチニブ（米日）ß アレクチニブ（日）

競争力の高いオンコロジーのためR&Dプロセスを変更

9

フォワード＆リバーストランスレーショナルリサーチプレシジョンメディシンに向けて

バイオマーカーによるアプローチはTRサイクルを推進し、成功確率（POS）を高め、製品価値を最大化する

大規模臨床・オミックス情報*を用いたリバースTR• 正しい標的と正しい患者を特定する• MOAの明確化• 適応の拡大• 有効な併用療法の同定

トランスレーショナルリサーチ(TR)イニシアティブ• 科学主導、データ主導の意思決定

*網羅的な生体分子についての情報であり、具体的にはゲノム（Genome）やトランスクリプトーム（Transcriptome）、プロテオーム（Proteome）、メタボローム（Metabolome）、インタラクトーム(Interactome)、セローム（Cellome）と呼ばれる、様々な網羅的な分子情報をまとめた情報、知識、集合のことを指す。日本オミックス医学会HPより

臨床試験

大規模臨床とオミックスデータ

前臨床試験

成功確率上昇製品価値最大化

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最先端のバイオIT オミックスプラットフォームの確立(OASIS: Oncology Analysis Scientific Information System)

第一三共の腫瘍分析科学情報システム(OASIS)は、腫瘍学における精密医学の開発に必要な深い分析を支援するグローバルで拡張可能な臨床/マルチオミックス/リアルワールドのデータプラットフォームである。

社内データ

リアルワールドデータ

遺伝子発現

遺伝子突然変異

臨床試験(SDTM*)

治療への反応治療家族歴

HERmark

遺伝子突然変異

細胞遺伝学的

エピゲノミクス

OASIS Platform

¸ アクセスコントロールと使用が管理されている¸ セキュリティ、プライバシー、コンプライアンス¸ データの統合・充実¸ アナリティクスの相互運用性¸ ネットワーク運用・共用サービス

(3)既存のパイプラインの価値を最大化する(新しい適応症、新しい併用療法など)

(1)生物学と安全性・有効性の関係の理解を深め、プレシジョンメディシンを推進

(2)患者ごとの疾患プロフィールを標的とした治療法の開発を加速し、成功の可能性を高める

*Study Data Tabulation Model：治験計画時に考慮する基準の1つ11





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バイオマーカー（BM）アッセイとCDxの開発

u 仮説設定• 創薬・開発を支援するバイオマーカーをどう見つけるか

u 臨床アッセイ開発• 非臨床から臨床へのバイオマーカーアッセイの移行を成功させるために、

何が必要か

u コンパニオン診断薬(CDx)開発• 日本でのCDx• CDxは単なるバイオマーカーアッセイではない• CDx開発のためのレギュラトリーおよびビジネス要件の理解

13

仮説設定(BMディスカバリー)

u 仮説ベースのディスカバリー• 標的分子の発現、例えば抗HER2抗体の細胞表面でのHER2発現

u 無仮説のディスカバリー• 「オミクックス」技術を用いた新しいバイオマーカーの同定• 細胞株パネル、例えばCCLE*のような多数のモデルを使用

u フォワード＆リバーストランスレーショナルリサーチ• フォワード:確立された非臨床モデルで仮説を立て、バイオマーカーを用いて

臨床試験/患者で確認する• リバース:臨床試験、病院、コンソーシアムでの臨床サンプル/データを利用して

仮説を立て、それを「コントロール可能な」非臨床研究で確認する

*Cancer Cell Line Encyclopedia

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臨床段階に入る前のBMディスカバリーと評価

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BMの選択

既存の生物学より

無仮説発見

BM陽性モデル vs BM陰性モデルにおける薬効

ヒトのサンプルで確認• 頻度• 疾患• 集団

標的疾患の適切なモデルは?

標的疾患のサンプルは?

適切なモデルをどのように見つけ/確立するか?

適切なサンプルをどのように取得するか?• 病院？

コンソーシアム?• バイオバンク?• 独自の試験?

ヒトのサンプルで正しく機能するアッセイか?

信頼できるアッセイをどのように開発するか?

Gerlinger et al. NEJM 2012

品質は?

臨床アッセイの開発

u 非臨床段階と比べ多くの不確実な要因がある• 実際の患者、サンプルの品質、ハンドリング、加工、技能、物流、

ヒューマンエラーなど

u 必要用件として求められるレベルが高くなる• レギュラトリー要件

分析妥当性、GLP、CAP/CLIA認証*• 臨床的要件

臨床的妥当性、試験デザイン• 実際の運用可能性

必ずしも熟練した技能者、研究者が扱うとは限らない

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*CAP（College of American Pathologists）は米国病理学会のことで、グルコース検査の標準化を目的に 1946 年に設立。CLIA（Clinical Laboratory Improvement Amendments）は 1988 年に米国連邦政府が法律として制定した臨床検査室改善法（CLIA法）。米国内の全ての臨床検査室は法に基づきCLIA認定を受ける必要がある。

日本のコンパニオン診断薬(CDx)

PMDA: in vitroコンパニオン診断薬および関連する治療製品の承認申請に関する届出

CDxは、当該治療薬の使用に必須であり、以下のいずれかに相当する:

• 特定の治療薬により良好に反応すると期待される患者を特定するために使用される

• 特定の治療薬に関連する有害事象の発現リスクが高いと思われる患者を特定するために使用される

• 特定の治療薬の用量、スケジュール、および投与中止を含む治療を最適化するために必要である

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コンパニオン診断薬(CDx)の開発

米国FDAより引用:「バイオマーカーとは、新しい生物医学的発見のペース（速い）と、これらの発見が治療へと開発されるペース（遅い）との間のギャップを埋める機会である」

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バイオマーカーの分析=研究開発のValue Proposition

http://www.fda.gov/default.htmhttp://www.fda.gov/default.htmhttp://www.fda.gov/default.htmhttp://www.fda.gov/default.htmhttp://www.hhs.gov/http://www.hhs.gov/http://images.google.com/imgres?imgurl=http://ocw.mit.edu/NR/rdonlyres/Economics/14-05Fall-2005/09E5E194-B250-42D0-82B6-11E7175AB3E2/0/chp_currency_1.jpg&imgrefurl=http://ocw.mit.edu/OcwWeb/Economics/14-05Fall-2005/CourseHome/&h=300&w=420&sz=61&tbnid=Dt_KvlH3BriSLM:&tbnh=89&tbnw=125&prev=/images?q=currency+photo&um=1&start=2&sa=X&oi=images&ct=image&cd=2http://images.google.com/imgres?imgurl=http://ocw.mit.edu/NR/rdonlyres/Economics/14-05Fall-2005/09E5E194-B250-42D0-82B6-11E7175AB3E2/0/chp_currency_1.jpg&imgrefurl=http://ocw.mit.edu/OcwWeb/Economics/14-05Fall-2005/CourseHome/&h=300&w=420&sz=61&tbnid=Dt_KvlH3BriSLM:&tbnh=89&tbnw=125&prev=/images?q=currency+photo&um=1&start=2&sa=X&oi=images&ct=image&cd=2

CDx製品の必要性を生み出すものは何か?

その他の考慮事項u 開発プログラムでの必要性

• 患者の層別化は、臨床試験のコストおよび期間をコントロールする手段である

u コマーシャルでの必要性

• 競合品との差別化

• より早い上市

u 医療経済

• 患者の治療に価値をもたらす薬剤に対し、ペイヤーの関心が高まりつつある

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診断薬は単なるアッセイではない

診断薬製品は、レギュレーションの対象となる最終製品を構成している、試薬、機器、ソフトウェア、アルゴリズム、手順を含む複雑なシステムである

20

サンプル採取サンプル処理受入検体抽出

医師の解釈データの解析マーカー検出

出荷

データのアーカイブアッセイの調製

医薬品とCDxの上市計画に必要な考慮事項

u 製品流通-上市時のサプライチェーンの確保

u 機器ベースおよび試験へのアクセスの提供

• グローバルでの開発・マーケティングへの対応

• ターンアラウンドタイム

u 営業、医師、サポートスタッフなどへの研修プログラム

u 製品問題報告を含む顧客サポート

u 現場の技術支援

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22

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-6 0

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-2 0

0

2 0

4 0

6 0

8 0

Ch

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fro

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%)

C o lo re c ta l

N S C L C

O th e r

-1 0 0

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%)

HER2陽性乳がん HER2-Low Breast Cancer

HER2発現その他のがんHER2-Positive Gastric Cancer

N = 104 N = 50

N = 44 N = 37

腫瘍タイプによる腫瘍縮小: (5.4 or 6.4 mg/kg)

HER2-Positive Breast Cancer, Gastric Cancer, HER2-Expressing Other cancers: ASCO 2018 PresentationIncludes subjects who had ≥1 postbaseline scan. Dotted lines denote 20% increase and 30% reduction in tumor size, respectively.*Confirmed response includes subjects who had ≥2 postbaseline scans, progressive disease, or discontinued treatment for any reason prior to second postbaseline scan.

Data cutoff is April 18, 2018.

DS-8201 ¦P1試験の有効性

HER2-Low Breast Cancer: Modi et al, SABCS, 2018; Poster # P6-17-02, Abstract #486

HER2低発現乳がん

HER2陽性胃がん

23

DS-8201 ¦CDx開発を検討中の臨床試験

乳がん

胃がん

大腸がん肺がん

併用

複数のがん種 P1

HER2陽性 T-DM1既治療乳がん申請用 P2

HER2陽性 T-DM1既治療乳がんvs 医師選択治療 P3

HER2陽性 vs T-DM1 P3

HER2 低発現 P3

HER2 発現胃がん 3rd ラインvs 医師選択治療 P2

HER2発現胃がん 2nd ライン vs 標準治療 P3

大腸がん P2

非小細胞肺がん P2

転移性乳がん・膀胱がんニボルマブ併用

転移性乳がん・非小細胞肺がんペムブロリズマブ併用

固形がんアベルマブ併用

固形がん TKI併用

追加併用プログラム

04

24

DS-8201 ¦患者選択とCDx開発戦略

25

DS-8201

HER2陽性乳がん、胃がん

HER2新規適応非小細胞肺がん、

大腸がんHER 変異HER2 低発現

HER2 低発現1+, 2+/ISH-

HER2最低値アッセイ*

将来のHER2 CDx(> 最低値) &

バイスタンダー効果の予測因子

併用

IHC/FISH 利用可能既存CDxの適応拡大新たなCDxを開発(NGS パネル)

今後定義

精査中新たなCDxを開発 (?)既存CDxの適応拡大 *DS-8201が有効な最低値を探索するアッセイ

メソッド標的アッセイのスキーム例

IHC HER2タンパク質

FISH HER2遺伝子

DISH HER2遺伝子

HER2 IHC (タンパク質)とISH (遺伝子)

赤く発色(Texas Red)

緑に発色l(FITC)

セントロメア領域 (CEN)

HER2領域(17q11.2-q2)

17番染色体

ＺHER2たん白

抗HER2抗体

二次抗体酵素

茶色に発色

50 mm

HER2 (3+) HER2 (-)

Amp (+) Amp (-)

Red/Black : 1.0Black : cluster

Amp (+) Amp (-)

陽性: 黒 (HER2)/赤 (CEN)≧ 2.0

陽性: 赤(HER2)/緑 (CEN) ≧ 2.0

陽性: HER2 3+

IHC: immunohistochemistry, FISH: fluorescent in situ hybridization, DISH: dual color in situ hybridization

https://www.agilent.com/cs/library/usermanuals/public/29037_her2fish_interpretation_guide_breast_us.pdf

http://www.roche-diagnostics.ch/content/dam/corporate/roche-dia_ch/documents/broschueren/tissue_diagnostics/Parameter/breast-pathology/06989217001_EN_EA_Interpretation-Guide-HER2-Dual-ISH-EN.pdf

組織切片

プローブプローブ

DIG

セントロメア領域 (CEN)

HER2領域(17q11.2-q2)

DNP酵素

酵素

17番染色体

黒く発色赤く発色

プローブプローブ

26

現在の乳がん診療におけるHER2 IHCスコアリング

27HER2 検査ガイド乳癌編[第4版]

現在の乳がん診療におけるHER2 ISHスコアリング

28HER2 検査ガイド乳癌編[第4版]

HER2の再定義

HER2は、1998年9月にIHC (細胞表面上のタンパク質の過剰発現)(ハーセプチンの承認)によって定義された。

HER2は、HER2経路に「依存」していると認識される腫瘍においてHER2の過剰活性化を遮断するように特別に設計されたHER2修飾薬(トラスツズマブ、ペルツズマブ、アファチニブ、ラパチニブ、ネラチニブ)によって同定されていた。

HER2 Low HER2 Neg

29

3+ 2+ 1+ -

HER2 High

タンパク質

mRNA

突然変異

cfRNA

DS-8201 ¦新規HER2評価の検討

30

新技術の評価

液体生検技術の活用

複数の新技術の評価既存技術の評価

既存技術の評価

cfDNA

DSは多くのテクノロジー・リーダーと提携

ROCHE Tissue Diagnostics細胞外ドメイン

DS-8201CDx Approach

U3-1402 ¦ファーストインクラスの可能性

31

HER3はADC スマートChemoの重要なターゲット

+同じADC技術

DAR8

パトリツマブ臨床で300例以上の

安全性と忍容性を確認済みのモノクローナル抗体

Source: Clin Cancer Res 2013 Jun 1;19(11):3078-87; Cancer Chemother Pharmacol 2014 Mar;73(3):511-6.

HER3発現乳がん試験でスクリーニングされた188人の患者

HER3 1+~29%

HER3 2+/3+~20%

HER3の発現は以下の多くのがん種で観察された。乳がん、肺がん、前立腺がん、大腸がん卵巣がん、膀胱がん、メラノーマなど

U3-1402 ¦ がん種によるHER3の発現

32

0102030405060708090

100

HER3 Expression in Cancer 3+ 2+ 1+ 0

Data from internal analysis using in-house IHC assay of cancer tissue samples (purchased TMA samples). Majority of tissue from primary tumor. Internal pathologist scored following HER3 scoring criteria.

(Sample number)

Graph3

HER3 Expression in Cancer

3+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)54.83870967741935241.57303370786517135.18518518518518335.65217391304347729.03225806451612832.81255031.06060606060606221.38728323699421816.12903225806451615.62522.58064516129032412.90322580645161219.2307692307692322.22222222222222112.82051282051282115.9090909090909081415.3846153846153854.25531914893617018.5365853658536598.88888888888888932.38095238095238092.22222222222222232.43902439024390243.448275862068965302+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)29.03225806451612837.07865168539326137.65432098765432335.65217391304347737.09677419354838432.812513.2075471698113231.06060606060606239.30635838150288935.48387096774193634.37525.80645161290322435.48387096774193625.64102564102564222.22222222222222130.7692307692307727.2727272727272732823.07692307692307727.65957446808510821.95121951219512421.11111111111111119.04761904761904715.5555555555555559.75609756097560955.172413793103448401+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)6.451612903225806111.23595505617977616.6666666666666682020.96774193548387226.562524.52830188679245234.84848484848485130.05780346820809335.48387096774193634.37535.48387096774193635.48387096774193641.02564102564102955.55555555555555725.64102564102564243.181818181818183830.7692307692307753.19148936170212525.60975609756097527.77777777777777938.09523809523809542.22222222222222165.85365853658537140.517241379310342300Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)9.6774193548387110.11235955056179810.4938271604938288.69565217391304312.9032258064516127.812512.2641509433962263.03030303030303039.248554913294798412.90322580645161215.62516.12903225806451616.12903225806451614.102564102564102030.7692307692307713.6363636363636372030.7692307692307714.89361702127659543.90243902439024742.22222222222222140.4761904761904744021.95121951219512450.86206896551723870

IHC score

HER3 IHC Score

0No membranous staining or staining of < 10% of the tumor cells

1+Staining is weak or detected in only one part of the membrane in ≥ 10% of the cells

2+Moderate/weak complete or partial membranous staining in ≥ 10% of the cells

3+Strong complete or partial membranous staining in ≥ 10% of the neoplastic cells

https://www.nichirei.co.jp/bio/infolibrary/pdf/her2_kit_atlas_1204.pdf#search='%E6%97%A5%E6%9C%AC%E7%97%85%E7%90%86%E5%AD%A6%E4%BC%9A+HER2'

胃がん症例における判定法（手術標本）イ

HER2判定（胃がん）イIHC 法の判定基準

・胃癌における判定方法は乳癌の場合と同様、細胞質における反応は判定の対象外とし、細胞膜における染色性およびその染色強度によって判定する。・手術標本の判定においては10% のカットオフ値（腫瘍細胞の10％以上が陽性）が適用されている（内視鏡生検標本の判定には切除標本とは異なり染色割合のカットオフ値を設定せず、5 個以上の癌細胞のクラスターが確認されれば陽性とする）。

胃がん症例におけるHER2判定法

スコア判定ハンテイ切除標本の染色パターン

0陰性細胞膜に陽性染色なし、あるいは細胞膜の陽性染色がある癌細胞が一切片に10％未満である。

1+陰性弱／ほとんど識別できないほどかすかな細胞膜の染色がある癌細胞が一切片に10％以上認められる。癌細胞は細胞膜のみが部分的に染色されている。

2+境界域弱～中程度の完全な側方あるいは側方・基底膜側の細胞膜の陽性染色がある。癌細胞が一切片に10％以上認められる。

3+陽性強い完全な側方あるいは側方・基底膜側の細胞膜の陽性染色がある癌細胞が一切片に10％以上認められる。全周性に認められない場合もある。

本判定基準はHofmann m, stoss o, shi D, buttner R, van de Vijver m, Kim W, et al. assessment of a HeR2 scoring system for gastric cancer: results from a

validation study. (Histopath 2008; 52:797-805) およびHeR2 検査ガイド胃癌編（胃癌トラスツズマブ病理部会作成）に基づいています。

胃癌におけるスコアリングの判定フローチャート

以下のフローチャートに従って判定します。

光学顕微鏡の2-4 倍対物レンズを使用して、腫瘍全体における細胞膜の染色性を確認してください。次に10-20 倍対物レンズで細胞膜への染色強度を評価します。必要に応じて、40倍対物レンズで確認してください。

ダコ Herceptest II による胃癌標本での評価手順

https://www.nichirei.co.jp/bio/infolibrary/pdf/her2_kit_atlas_1204.pdf

Fig All order Reverse

Number of coresNumber of cores with tumors3+2+1+0Total2+/3+

Skin_Melanoma (31)55296103110084

Breast_HER2+ (89)423711108910079

Breast_ER+ (162)3538171016210073

Ovary_Serous ca (115)363620911510071

Breast_TN (62)293721136210066

Stomach_Intestinal type AC (64)33332786410066

Bladder_TCC (106)5013251210610063

Prostate_AC (132)313135313210062

Colon_AC (173)213930917310061

Pancreas_AC (62)163535136210052

Lung_NSCLC_LCC (32)163434163210050

Esophagus_AC (31)232635163110048

Biliary duct_AC (31)133535163110048

Lung_NSCLC_AC (78)192641147810045

Ovary_Clear cell (9)2222560910044

H&N_Salivary gl. Ca (78)133126317810044

Kidney_pRC (44)162743144410043

Lung_NSCLC_SCC (50)142838205010042

Ovary_Mucinous (13)152331311310038

Stomach_Diffuse type AC (47)42853154710032

Uterus_Endometrial ca (82)92226448210030

H&N_SCC (90)92128429010030

Ovary_Endometrioid (42)21938404210021TN: triple negative

Esophagus_SCC (45)21642404510018AC: adenocarcinoma

Kidney_ccRC (41)21066224110012SCC: squamous cell carcinoma

Liver_HCC (116)3541511161009LCC: large cell carcinoma

Thyroid_Follicular and papillary ca (40)003070401000TCC: transitional cell carcinoma

106106pRC: papillary renal cell carcinoma

ccRC: clear cell renal cell carcinoma


0Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)9.6774193548387110.11235955056179810.4938271604938288.69565217391304312.9032258064516127.812512.2641509433962263.03030303030303039.248554913294798412.90322580645161215.62516.12903225806451616.12903225806451614.102564102564102030.7692307692307713.6363636363636372030.7692307692307714.89361702127659543.90243902439024742.22222222222222140.4761904761904744021.95121951219512450.862068965517238701+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)6.451612903225806111.23595505617977616.6666666666666682020.96774193548387226.562524.52830188679245234.84848484848485130.05780346820809335.48387096774193634.37535.48387096774193635.48387096774193641.02564102564102955.55555555555555725.64102564102564243.181818181818183830.7692307692307753.19148936170212525.60975609756097527.77777777777777938.09523809523809542.22222222222222165.85365853658537140.517241379310342302+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)29.03225806451612837.07865168539326137.65432098765432335.65217391304347737.09677419354838432.812513.2075471698113231.06060606060606239.30635838150288935.48387096774193634.37525.80645161290322435.48387096774193625.64102564102564222.22222222222222130.7692307692307727.2727272727272732823.07692307692307727.65957446808510821.95121951219512421.11111111111111119.04761904761904715.5555555555555559.75609756097560955.172413793103448403+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)54.83870967741935241.57303370786517135.18518518518518335.65217391304347729.03225806451612832.81255031.06060606060606221.38728323699421816.12903225806451615.62522.58064516129032412.90322580645161219.2307692307692322.22222222222222112.82051282051282115.9090909090909081415.3846153846153854.25531914893617018.5365853658536598.88888888888888932.38095238095238092.22222222222222232.43902439024390243.44827586206896530

Cancer type

% of HER3 expression


3+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)54.83870967741935241.57303370786517135.18518518518518335.65217391304347729.03225806451612832.81255031.06060606060606221.38728323699421816.12903225806451615.62522.58064516129032412.90322580645161219.2307692307692322.22222222222222112.82051282051282115.9090909090909081415.3846153846153854.25531914893617018.5365853658536598.88888888888888932.38095238095238092.22222222222222232.43902439024390243.448275862068965302+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)29.03225806451612837.07865168539326137.65432098765432335.65217391304347737.09677419354838432.812513.2075471698113231.06060606060606239.30635838150288935.48387096774193634.37525.80645161290322435.48387096774193625.64102564102564222.22222222222222130.7692307692307727.2727272727272732823.07692307692307727.65957446808510821.95121951219512421.11111111111111119.04761904761904715.5555555555555559.75609756097560955.172413793103448401+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)6.451612903225806111.23595505617977616.6666666666666682020.96774193548387226.562524.52830188679245234.84848484848485130.05780346820809335.48387096774193634.37535.48387096774193635.48387096774193641.02564102564102955.55555555555555725.64102564102564243.181818181818183830.7692307692307753.19148936170212525.60975609756097527.77777777777777938.09523809523809542.22222222222222165.85365853658537140.517241379310342300Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Clear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)9.6774193548387110.11235955056179810.4938271604938288.69565217391304312.9032258064516127.812512.2641509433962263.03030303030303039.248554913294798412.90322580645161215.62516.12903225806451616.12903225806451614.102564102564102030.7692307692307713.6363636363636372030.7692307692307714.89361702127659543.90243902439024742.22222222222222140.4761904761904744021.95121951219512450.86206896551723870

Fig 3+

Number of coresNumber of cores with tumors3+

Skin_Melanoma (31)55

Bladder_TCC (106)50

Breast_HER2+ (89)42

Ovary_Serous ca (115)36

Breast_ER+ (162)35


Prostate_AC (132)31

Breast_TN (62)29

Esophagus_AC (31)23

Ovary_Cear cell (9)22

Colon_AC (173)21

Lung_NSCLC_AC (78)19

Pancreas_AC (62)16

Kidney_pRC (44)16

Lung_NSCLC_LCC (32)16

Ovary_Mucinous (13)15

Lung_NSCLC_SCC (50)14

Biliary duct_AC (31)13

H&N_Salivary gl. Ca (78)13

H&N_SCC (90)9

Uterus_Endometrial ca (82)9TN: triple negative

Stomach_Diffuse type AC (47)4AC: adenocarcinoma

Liver_HCC (116)3SCC: squamous cell carcinoma

Kidney_ccRC (41)2LCC: large cell carcinoma

Ovary_Endometrioid (42)2TCC: transitional cell carcinoma

Esophagus_SCC (45)2pRC: papillary renal cell carcinoma

Thyroid_Follicular and papillary ca (40)0ccRC: clear cell renal cell carcinoma

106106

3+ HER3 Expression in Cancer

3+Skin_Melanoma (31)Bladder_TCC (106)Breast_HER2+ (89)Ovary_Serous ca (115)Breast_ER+ (162)Stomach_Intestinal type AC (64)Prostate_AC (132)Breast_TN (62)Esophagus_AC (31)Ovary_Cear cell (9)Colon_AC (173)Lung_NSCLC_AC (78)Pancreas_AC (62)Kidney_pRC (44)Lung_NSCLC_LCC (32)Ovary_Mucinous (13)Lung_NSCLC_SCC (50)Biliary duct_AC (31)H&N_Salivary gl. Ca (78)H&N_SCC (90)Uterus_Endometrial ca (82)Stomach_Diffuse type AC (47)Liver_HCC (116)Kidney_ccRC (41)Ovary_Endometrioid (42)Esophagus_SCC (45)Thyroid_Follicular and papillary ca (40)54.8387096774193525041.57303370786517135.65217391304347735.18518518518518332.812531.06060606060606229.03225806451612822.58064516129032422.22222222222222121.38728323699421819.2307692307692316.12903225806451615.90909090909090815.62515.3846153846153851412.90322580645161212.8205128205128218.88888888888888938.5365853658536594.25531914893617013.44827586206896532.43902439024390242.38095238095238092.22222222222222230

Cancer type

% of 3+ HER3 expresion

Fig 2+&3+

Number of coresNumber of cores with tumors2+/3+

Skin_Melanoma (31)84

Breast_HER2+ (89)79

Breast_ER+ (162)73

Ovary_Serous ca (115)71

Breast_TN (62)66


Bladder_TCC (106)63

Prostate_AC (132)62

Colon_AC (173)61

Pancreas_AC (62)52

Lung_NSCLC_LCC (32)50

Esophagus_AC (31)48

Biliary duct_AC (31)48

Lung_NSCLC_AC (78)45


H&N_Salivary gl. Ca (78)44

Kidney_pRC (44)43

Lung_NSCLC_SCC (50)42

Ovary_Mucinous (13)38


Uterus_Endometrial ca (82)30TN: triple negative

H&N_SCC (90)30AC: adenocarcinoma

Ovary_Endometrioid (42)21SCC: squamous cell carcinoma

Esophagus_SCC (45)18LCC: large cell carcinoma

Kidney_ccRC (41)12TCC: transitional cell carcinoma

Liver_HCC (116)9pRC: papillary renal cell carcinoma

Thyroid_Follicular and papillary ca (40)0ccRC: clear cell renal cell carcinoma

106106

2+/3+ HER3 Expression in Cancer

2+/3+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Cear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)83.87096774193548878.65168539325843372.83950617283950671.30434782608695366.12903225806451265.62563.2075471698113262.12121212121212560.69364161849711151.6129032258064485048.38709677419355248.38709677419355244.87179487179486944.44444444444444343.58974358974359143.181818181818184238.4615384615384631.91489361702127830.4878048780487813021.42857142857142717.777777777777779128.62068965517241460

Cancer type

% of 2+/3+ HER3 expression

Sarcoma Fig

DS #DS coordinatesscorefindingsnoteTu/NATDS #DS coordinatesDiagnosis short

1x3y1-Lostfattumorosteosarcoma1x3y1osteosarcoma

2x4y1000tumorosteosarcoma2x4y1osteosarcoma


4x6y1-no tumor0tumorosteosarcoma4x6y1osteosarcoma



7x9y1-Few tumor cells0tumorosteosarcoma7x9y1osteosarcoma






13x15y100骨近傍の細胞のｃｙｔにsignaltumorosteosarcoma13x15y1osteosarcoma

14x16y13+0ｃｙｔ 3+tumorrhabdomyosarcoma14x16y1rhabdomyosarcoma

15x1y23+0膜は不明　ほぼすべての細胞tumorrhabdomyosarcoma15x1y2rhabdomyosarcoma

16x2y2000tumorrhabdomyosarcoma16x2y2rhabdomyosarcoma

17x3y21+0ごく一部の細胞tumorrhabdomyosarcoma17x3y2rhabdomyosarcoma

18x4y21+0ほぼすべての細胞tumorrhabdomyosarcoma18x4y2rhabdomyosarcoma

19x5y21+0一部の細胞tumorrhabdomyosarcoma19x5y2rhabdomyosarcoma






25x11y2000tumorLeiomyosarkom25x11y2Leiomyosarkom
















41x11y3-Few tumor cells0tumorLiposarkom41x11y3Liposarkom

42x12y3000tumorLiposarkom42x12y3Liposarkom



45x15y3ERROR:#REF!ERROR:#REF!0tumorLiposarkom45x15y3Liposarkom










55x9y4-no tumor0tumorLiposarkom55x9y4Liposarkom

56x10y4000tumorAngiosarkom56x10y4Angiosarkom



59x13y4-Few tumor cells0tumorAngiosarkom59x13y4Angiosarkom


61x15y41+0一部の細胞の膜tumorAngiosarkom61x15y4Angiosarkom

62x16y41+0一部の細胞, cytnucleartumorMPNST62x16y4MPNST

63x1y52+0膜は不明　ほぼすべての細胞tumorMPNST63x1y5MPNST

64x2y51+0一部の細胞tumorMPNST64x2y5MPNST

65x3y5000tumorMPNST65x3y5MPNST


67x5y500nucleartumorMPNST67x5y5MPNST








75x13y51+0cyt, non-speの可能性tumorMPNST75x13y5MPNST


77x15y51+0ごくわずかtumorMPNST77x15y5MPNST

78x16y5000tumorMyxofibrosarkom78x16y5Myxofibrosarkom




82x4y6-Lost0tumorMyxofibrosarkom82x4y6Myxofibrosarkom




86x8y6-Lost0tumorMyxofibrosarkom86x8y6Myxofibrosarkom



89x11y6000tumorGIST89x11y6GIST






95x1y700nucleartumorGIST95x1y7GIST









104x10y7000tumorGIST01+2+3+-Total104x10y7GIST

105x11y7000tumorGISTCore7893411105105x11y7GIST

106x12y7000tumorGIST%831034106x12y7GIST

# evaluable# positive

Osteosarcoma700

Rhabdomyosarcoma114/1+, 2/2+, 3/3+9

Leiomyosarcoma1500

Liposarcoma1200

Angiosarcoma51/1+1

MPNST154/1+, 1/2+, 1/3+6

Myxofibrosarcoma900

GIST1800

# positive# negative# evaluable

Osteosarcoma077

Rhabdomyosarcoma9211

Leiomyosarcoma01515

Liposarcoma01212

Angiosarcoma145

MPNST6915

Myxofibrosarcoma099

GIST01818

01+2+3+82.9787234042553199.57446808510638373.19148936170212764.2553191489361701

HER3 Expression in Sarcoma

# positiveOsteosarcomaRhabdomyosarcomaLeiomyosarcomaLiposarcomaAngiosarcomaMPNSTMyxofibrosarcomaGIST09001600# negativeOsteosarcomaRhabdomyosarcomaLeiomyosarcomaLiposarcomaAngiosarcomaMPNSTMyxofibrosarcomaGIST72151249918

Sarcoma

Number of cores

Fig All order

Number of coresNumber of cores with tumors01+2+3+Total2+/3+

Skin_Melanoma (31)10629553110084

Breast_HER2+ (89)101137428910079

Breast_ER+ (162)1017383516210073

Ovary_Serous ca (115)920363611510071

Breast_TN (62)132137296210066


Bladder_TCC (106)1225135010610063

Prostate_AC (132)335313113210062

Colon_AC (173)930392117310061

Pancreas_AC (62)133535166210052

Lung_NSCLC_LCC (32)163434163210050

Esophagus_AC (31)163526233110048

Biliary duct_AC (31)163535133110048

Lung_NSCLC_AC (78)144126197810045


H&N_Salivary gl. Ca (78)312631137810044

Kidney_pRC (44)144327164410043

Lung_NSCLC_SCC (50)203828145010042

Ovary_Mucinous (13)313123151310038



H&N_SCC (90)42282199010030

Ovary_Endometrioid (42)40381924210021TN: triple negative

Esophagus_SCC (45)40421624510018AC: adenocarcinoma

Kidney_ccRC (41)22661024110012SCC: squamous cell carcinoma

Liver_HCC (116)5141531161009LCC: large cell carcinoma

Thyroid_Follicular and papillary ca (40)703000401000TCC: transitional cell carcinoma

106106pRC: papillary renal cell carcinoma



Osteosarcoma700


Leiomyosarkom1500

Liposarkom1200

Angiosarkom51/1+1

MPNST154/1+, 1/2+, 1/3+6

Myxofibrosarcoma900

GIST1800

Ovary

Endometrioid

01+2+3+-Total#evaluable

Core17168114342

%4038192100

Mucinous

01+2+3+-Total

Core443221513

%31312315100

Clear cell

01+2+3+-Total

Core05224139

%0562222100

Kidney

ccRC

01+2+3+-Total

Core9274174841

%2266102100

pRC

01+2+3+-Total

Core61912744844

%14432716100


0Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Cear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)9.6774193548387110.11235955056179810.4938271604938288.69565217391304312.9032258064516127.812512.2641509433962263.03030303030303039.248554913294798412.90322580645161215.62516.12903225806451616.12903225806451614.102564102564102030.7692307692307713.6363636363636372030.7692307692307714.89361702127659543.90243902439024742.22222222222222140.4761904761904744021.95121951219512450.862068965517238701+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Cear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)6.451612903225806111.23595505617977616.6666666666666682020.96774193548387226.562524.52830188679245234.84848484848485130.05780346820809335.48387096774193634.37535.48387096774193635.48387096774193641.02564102564102955.55555555555555725.64102564102564243.181818181818183830.7692307692307753.19148936170212525.60975609756097527.77777777777777938.09523809523809542.22222222222222165.85365853658537140.517241379310342302+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Cear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)29.03225806451612837.07865168539326137.65432098765432335.65217391304347737.09677419354838432.812513.2075471698113231.06060606060606239.30635838150288935.48387096774193634.37525.80645161290322435.48387096774193625.64102564102564222.22222222222222130.7692307692307727.2727272727272732823.07692307692307727.65957446808510821.95121951219512421.11111111111111119.04761904761904715.5555555555555559.75609756097560955.172413793103448403+Skin_Melanoma (31)Breast_HER2+ (89)Breast_ER+ (162)Ovary_Serous ca (115)Breast_TN (62)Stomach_Intestinal type AC (64)Bladder_TCC (106)Prostate_AC (132)Colon_AC (173)Pancreas_AC (62)Lung_NSCLC_LCC (32)Esophagus_AC (31)Biliary duct_AC (31)Lung_NSCLC_AC (78)Ovary_Cear cell (9)H&N_Salivary gl. Ca (78)Kidney_pRC (44)Lung_NSCLC_SCC (50)Ovary_Mucinous (13)Stomach_Diffuse type AC (47)Uterus_Endometrial ca (82)H&N_SCC (90)Ovary_Endometrioid (42)Esophagus_SCC (45)Kidney_ccRC (41)Liver_HCC (116)Thyroid_Follicular and papillary ca (40)54.83870967741935241.57303370786517135.18518518518518335.65217391304347729.03225806451612832.81255031.06060606060606221.38728323699421816.12903225806451615.62522.58064516129032412.90322580645161219.2307692307692322.22222222222222112.82051282051282115.9090909090909081415.3846153846153854.25531914893617018.5365853658536598.88888888888888932.38095238095238092.22222222222222232.43902439024390243.44827586206896530

Cancer type

% of HER3 expression

Fig All

Number of coresNumber of cores with tumors01+2+3+Total2+/3+

Esophagus_AC (31)163526233110048

Esophagus_SCC (45)40421624510018

Lung_NSCLC_AC (78)144126197810045

Lung_NSCLC_SCC (50)203828145010042

Lung_NSCLC_LCC (32)163434163210050

Pancreas_AC (62)133535166210052

Biliary duct_AC (31)163535133110048

Breast_ER+ (162)1017383516210073

Breast_HER2+ (89)101137428910079

Breast_TN (62)132137296210066

Skin_Melanoma (31)10629553110084



Colon_AC (173)930392117310061

Ovary_Serous ca (115)920363611510071

Ovary_Endometrioid (42)40381924210021

Ovary_Mucinous (13)313123151310038


H&N_SCC (90)42282199010030

H&N_Salivary gl. Ca (78)312631137810044

Liver_HCC (116)5141531161009

Bladder_TCC (106)1225135010610063

Prostate_AC (132)335313113210062


Kidney_ccRC (41)22661024110012

Kidney_pRC (44)144327164410043

Thyroid_Follicular and papillary ca (40)703000401000TN: triple negative

106106AC: adenocarcinoma

SCC: squamous cell carcinoma

LCC: large cell carcinoma

TCC: transitional cell carcinoma

pRC: papillary renal cell carcinoma



Osteosarcoma700


Leiomyosarkom1500

Liposarkom1200

Angiosarkom51/1+1

MPNST154/1+, 1/2+, 1/3+6

Myxofibrosarcoma900

GIST1800

Ovary

Endometrioid

01+2+3+-Total#evaluable

Core17168114342

%4038192100

Mucinous

01+2+3+-Total

Core443221513

%31312315100

Clear cell

01+2+3+-Total

Core05224139

%0562222100

Kidney

ccRC

01+2+3+-Total

Core9274174841

%2266102100

pRC

01+2+3+-Total

Core61912744844

%14432716100


0Esophagus_AC (31)Esophagus_SCC (45)Lung_NSCLC_AC (78)Lung_NSCLC_SCC (50)Lung_NSCLC_LCC (32)Pancreas_AC (62)Biliary duct_AC (31)Breast_ER+ (162)Breast_HER2+ (89)Breast_TN (62)Skin_Melanoma (31)Stomach_Intestinal type AC (64)Stomach_Diffuse type AC (47)Colon_AC (173)Ovary_Serous ca (115)Ovary_Endometrioid (42)Ovary_Mucinous (13)Ovary_Cear cell (9)H&N_SCC (90)H&N_Salivary gl. Ca (78)Liver_HCC (116)Bladder_TCC (106)Prostate_AC (132)Uterus_Endometrial ca (82)Kidney_ccRC (41)Kidney_pRC (44)Thyroid_Follicular and papillary ca (40)16.1290322580645164014.1025641025641022015.62512.90322580645161216.12903225806451610.49382716049382810.11235955056179812.9032258064516129.677419354838717.812514.8936170212765959.24855491329479848.69565217391304340.47619047619047430.76923076923077042.22222222222222130.7692307692307750.86206896551723812.2641509433962263.030303030303030343.90243902439024721.95121951219512413.636363636363637701+Esophagus_AC (31)Esophagus_SCC (45)Lung_NSCLC_AC (78)Lung_NSCLC_SCC (50)Lung_NSCLC_LCC (32)Pancreas_AC (62)Biliary duct_AC (31)Breast_ER+ (162)Breast_HER2+ (89)Breast_TN (62)Skin_Melanoma (31)Stomach_Intestinal type AC (64)Stomach_Diffuse type AC (47)Colon_AC (173)Ovary_Serous ca (115)Ovary_Endometrioid (42)Ovary_Mucinous (13)Ovary_Cear cell (9)H&N_SCC (90)H&N_Salivary gl. Ca (78)Liver_HCC (116)Bladder_TCC (106)Prostate_AC (132)Uterus_Endometrial ca (82)Kidney_ccRC (41)Kidney_pRC (44)Thyroid_Follicular and papillary ca (40)35.48387096774193642.22222222222222141.0256410256410293834.37535.48387096774193635.48387096774193616.66666666666666811.23595505617977620.9677419354838726.451612903225806126.562553.19148936170212530.0578034682080932038.09523809523809530.7692307692307755.55555555555555727.77777777777777925.64102564102564240.51724137931034224.52830188679245234.84848484848485125.60975609756097565.85365853658537143.18181818181818302+Esophagus_AC (31)Esophagus_SCC (45)Lung_NSCLC_AC (78)Lung_NSCLC_SCC (50)Lung_NSCLC_LCC (32)Pancreas_AC (62)Biliary duct_AC (31)Breast_ER+ (162)Breast_HER2+ (89)Breast_TN (62)Skin_Melanoma (31)Stomach_Intestinal type AC (64)Stomach_Diffuse type AC (47)Colon_AC (173)Ovary_Serous ca (115)Ovary_Endometrioid (42)Ovary_Mucinous (13)Ovary_Cear cell (9)H&N_SCC (90)H&N_Salivary gl. Ca (78)Liver_HCC (116)Bladder_TCC (106)Prostate_AC (132)Uterus_Endometrial ca (82)Kidney_ccRC (41)Kidney_pRC (44)Thyroid_Follicular and papillary ca (40)25.80645161290322415.55555555555555525.6410256410256422834.37535.48387096774193635.48387096774193637.65432098765432337.07865168539326137.09677419354838429.03225806451612832.812527.65957446808510839.30635838150288935.65217391304347719.04761904761904723.07692307692307722.22222222222222121.11111111111111130.769230769230775.172413793103448413.2075471698113231.06060606060606221.9512195121951249.756097560975609527.27272727272727303+Esophagus_AC (31)Esophagus_SCC (45)Lung_NSCLC_AC (78)Lung_NSCLC_SCC (50)Lung_NSCLC_LCC (32)Pancreas_AC (62)Biliary duct_AC (31)Breast_ER+ (162)Breast_HER2+ (89)Breast_TN (62)Skin_Melanoma (31)Stomach_Intestinal type AC (64)Stomach_Diffuse type AC (47)Colon_AC (173)Ovary_Serous ca (115)Ovary_Endometrioid (42)Ovary_Mucinous (13)Ovary_Cear cell (9)H&N_SCC (90)H&N_Salivary gl. Ca (78)Liver_HCC (116)Bladder_TCC (106)Prostate_AC (132)Uterus_Endometrial ca (82)Kidney_ccRC (41)Kidney_pRC (44)Thyroid_Follicular and papillary ca (40)22.5806451612903242.222222222222222319.230769230769231415.62516.12903225806451612.90322580645161235.18518518518518341.57303370786517129.03225806451612854.83870967741935232.81254.255319148936170121.38728323699421835.6521739130434772.380952380952380915.38461538461538522.2222222222222218.888888888888889312.8205128205128213.44827586206896535031.0606060606060628.5365853658536592.439024390243902415.9090909090909080

Request

University Basel TMA

BlockOrganTumor typeNumber of coresNumber of cores with tumors01+2+3+Total2+/3+

DS_1-1EsophagusAdeno Ca45324974

DS_1-1_suppl1213

5118731

Esophagus_AC311635262310048

DS_2-1EsophagusSCC735018197145

Esophagus_SCC45404216210018

DS_3-1LungNSCLC_ACC118931132201578

Lung_NSCLC_AC781441261910045

DS_4-1LungNSCLC_SCC11187101914750

Lung_NSCLC_SCC502038281410042

DS_5-1LungNSCLC_LCC654651111532

Lung_NSCLC_LCC321634341610050

DS_6-1PancreasAdeno Ca9472822221062

Pancreas_AC621335351610052

DS_7-1Biliary ductAdeno Ca725851111431

Biliary duct_AC311635351310048

DS_8.1-1BreastER positive110881111222771

DS_8.2-1BreastER positive127102616393091

17276157162

Breast_ER+1621017383510073

DS_9-2BreastHER2 positive128100910333789

Breast_HER2+891011374210079

DS_10-1BreastTriple negative10080813231862

Breast_TN621321372910066

DS_11-1SkinMelanoma43363291731

Skin_Melanoma31106295510084

DS_12-1StomachIntestinal type adeno Ca8868517212164

Stomach_Intestinal type AC64827333310066

DS_13-2StomachDiffuse type adeno Ca614972513247

Stomach_Diffuse type AC47155328410032

DS_14.1-1ColonAdeno Ca12092822322082

DS_14.2-1ColonAdeno Ca142107830361791

16526837173

Colon_AC173930392110061

DS_17-1OvarySerous Ca12112110234141115

Ovary_Serous ca115920363610071

DS_18-1OvaryMucinous, endometriod ca 7373212615668

??????68313822910031

DS_19-1H&NSCC9898382519890

H&N_SCC90422821910030

DS_20-1 H&NSalivary gland Ca97842420241078

H&N_Salivary gl. Ca783126311310044

DS_21-2Skin, Lung, Esophagus, Stomach, Ileum, Colon, Pancreas, Liver, Kidney, BladderNormal100

DS_22-2Lymph node, Thymus, Spleen, Breast, Prostate, Uterus, Myometrium, Testis, Thyroid, Skeletal muscle, Smooth muscle, HeartNormal130

DS_23.1-2LiverHCC976923365367

DS_23.2-1LiverHCC1036336111149

594764116

Liver_HCC1165141531009

DS_24-2BladderTransitional cell Ca11811813261453106

Bladder_ TCC1061225135010063

DS_25.1-1ProstateAdeno Ca8568022202567

DS_25.2-1ProstateAdeno Ca8568424211665

4464141132

Prostate_AC132335313110062

DS_26-1UterusEndometrial Ca10598362118782

Uterus_Endometrial ca82442622910030

DS_27-1KidneyClear and papillary Ca12096154616885

Kidney_Clear and papillary ca85185419910028

DS_28-2ThyroidFollicular, papillary524028120040

Thyroid_Follicular and papillary ca407030001000

DS_29-1Bone, soft tissueSarcoma106106


Osteosarcoma700


Leiomyosarkom1500

Liposarkom1200

Angiosarkom51/1+1

MPNST154/1+, 1/2+, 1/3+6

Myxofibrosarcoma900

GIST1800

Ovary

Endometrioid

01+2+3+-Total

Core171681143

%4038192

Mucinous

01+2+3+-Total

Core4432215

%31312315

Clear cell

01+2+3+-Total

Core0522413

%0562222

Kidney

ccRC

01+2+3+-Total

Core92741748

%2266102

pRC

01+2+3+-Total

Core619127448

%14432716

Summary

DS1-1Esophageal adenocarcinoma

01+2+3+-Total

Core497483224

%17382917100Esophagus AC

DS1-1 summaryEsophageal adenocarcinoma

01+2+3+-Total

Core1213077

%14291443100

5118731

16%35%26%23%1

DS2-1Eso SCC

01+2+3+-Total

Core18197155045

%4042162100

DS03 NSCLC ACC

01+2+3+-Total

Core11322015159378

%14412619

DS04-1 NSCLC SCC

01+2+3+-Total

Core1019147247450

%20382814

DS05-1 NSCLC LCC

01+2+3+-Total

Core511115134532

%16343416

DS06-1 Panc Ade Ca

01+2+3+-Total

Core822221087062

%13353516

DS07-1 Biliary duct

01+2+3+-Total

Core511114184931

%16353513

DS08-1 BRC ER+

01+2+3+-Total

Core1111222747571

%15153138

DS08-2 BRC ER+

01+2+3+-Total

Core61639301010191

%7184333

DS09-2 BRC HER2+

01+2+3+-Total

Core91033371110089

%10113742

DS10-1 TNBC

01+2+3+-Total

Core8132318188062

%13213729

DS11-1 Skin Melanoma

01+2+3+-Total

Core3291753631

%1062955

DS12-1 Sto intestinal

01+2+3+-Total

Core517212146864

%8273333

　DS13-2 Sto Diffuse type

01+2+3+-Total

Core72513224947

%1553284

DS14-1 Colon AdeCa

01+2+3+-Total

Core8223220109282

%10273924

DS14-2 Colon AdeCa

01+2+3+-Total

Core83036171610791

%9334019

DS17-1 Ovary Serous

01+2+3+-Total

Core102341415120115

%9203636

DS18-1 Ovary MucinousOvary

01+2+3+-TotalEndometrioid

Core21261562706801+2+3+-Total

%3138229Core171681143

%4038192

DS19-1 H&N SCC

01+2+3+-TotalMucinous

Core38251988989001+2+3+-Total

%4228219Core4432215

%31312315

DS20-1 H&N Salivary gl ca

01+2+3+-Total

Core2420241068478Clear cell

%3126311301+2+3+-Total

Core0522413

%0562222

DS23.1 Liver HCC

01+2+3+-Total

Core23365326967

%345474

DS23.2 Liver HCC

01+2+3+-Total

Core36111175649

%732222

DS24-2 Bladder TCC

01+2+3+-Total

Core1326145312118106

%12251350

DS25.1 Prostate Adenoca

01+2+3+-Total

Core022202516867

%0333037


01+2+3+-Total

Core424211636865

%6373225

DS26-1 Uterus Endometrial ca

01+2+3+-Total

Core3621187169882

%4426229

DS27-1 Kidney pap clear caKidney

01+2+3+-TotalccRC

Core154616811968501+2+3+-Total

%1854199Core9274174841

%2266102

pRC

DS28-2 Thyroid Folli Papi01+2+3+-Total

01+2+3+-TotalCore61912744844

Core28120004040%14432716

%703000

DS29-1 Sarcomaindividual cancer

01+2+3+-Total

Core789341110594

%831034


Osteosarcoma700


Leiomyosarkom1500

Liposarkom1200

Angiosarkom51/1+1

MPNST154/1+, 1/2+, 1/3+6

Myxofibrosarcoma900

Ovary

Endometrioid

01+2+3+-Total

Core17168114342

%4038192

Mucinous

01+2+3+-Total

Core443221513

%31312315

Clear cell

01+2+3+-Total

Core05224139

%0562222

DS29-1 Sarcoma

DS #DS coordinatesscorefindingsnoteTu/NATDS #DS coordinatesDiagnosis short

1x3y1-Lostfattumorosteosarcoma1x3y1osteosarcoma












13x15y100骨近傍の細胞のｃｙｔにsignaltumorosteosarcoma13x15y1osteosarcoma

14x16y13+0ｃｙｔ 3+tumorrhabdomyosarcoma14x16y1rhabdomyosarcoma



17x3y21+0ごく一部の細胞tumorrhabdomyosarcoma17x3y2rhabdomyosarcoma




























45x15y3ERROR:#REF!ERROR:#REF!0tumorLiposarkom45x15y3Liposarkom










55x9y4-no tumor0tumorLiposarkom55x9y4Liposarkom




59x13y4-Few tumor cells0tumorAngiosarkom59x13y4Angiosarkom


61x15y41+0一部の細胞の膜tumorAngiosarkom61x15y4Angiosarkom

62x16y41+0一部の細胞, cytnucleartumorMPNST62x16y4MPNST


64x2y51+0一部の細胞tumorMPNST64x2y5MPNST



67x5y500nucleartumorMPNST67x5y5MPNST








75x13y51+0cyt, non-speの可能性tumorMPNST75x13y5MPNST


77x15y51+0ごくわずかtumorMPNST77x15y5MPNST


79x1y6000tumorMyxofibrosarkom# evaluable# positive79x1y6Myxofibrosarkom

80x2y6000tumorMyxofibrosarkomOsteosarcoma70080x2y6Myxofibrosarkom

81x3y6000tumorMyxofibrosarkomRhabdomyosarcoma114/1+, 2/2+, 3/3+981x3y6Myxofibrosarkom

82x4y6-Lost0tumorMyxofibrosarkomLeiomyosarkom150082x4y6Myxofibrosarkom

83x5y6000tumorMyxofibrosarkomLiposarkom120083x5y6Myxofibrosarkom

84x6y6000tumorMyxofibrosarkomAngiosarkom51/1+184x6y6Myxofibrosarkom

85x7y6000tumorMyxofibrosarkomMPNST154/1+, 1/2+, 1/3+685x7y6Myxofibrosarkom

86x8y6-Lost0tumorMyxofibrosarkomMyxofibrosarcoma90086x8y6Myxofibrosarkom

87x9y6000tumorMyxofibrosarkomGIST180087x9y6Myxofibrosarkom








95x1y700nucleartumorGIST95x1y7GIST









104x10y7000tumorGIST01+2+3+-Total104x10y7GIST

105x11y7000tumorGISTCore7893411105105x11y7GIST

106x12y7000tumorGIST%831034106x12y7GIST

01+2+3+82.9787234042553199.57446808510638373.19148936170212764.2553191489361701

DS28-2 Thyroid Folli Papi

DS #DS x/yscorefindingsnoteTu/non-TuDS-28_2 %TumorPathology diagnosis

1x3y1000Tu100follicular Thyroid Ca




9x11y100nuclearTu100follicular Thyroid Ca



13x15y100nuclearTu100follicular Thyroid Ca






19x5y21+00Tu90follicular Thyroid Ca


23x9y2000Tu100papillary Thyroid Ca

25x11y21+00Tu100papillary Thyroid Ca















45x15y31+0もっとも目立つTu100papillary Thyroid Ca









2x4y1000non-Tuokfollicular Thyroid Ca



8x10y100nuclearnon-Tuokfollicular Thyroid Ca

10x12y100nuclearnon-Tuokfollicular Thyroid Ca

22x8y200nuclearnon-Tuokpapillary Thyroid Ca




30x16y200nuclearnon-Tuokpapillary Thyroid Ca01+2+3+-Total

32x2y300nuclearnon-Tuokpapillary Thyroid CaCore281200040

34x4y300nuclearnon-Tuokpapillary Thyroid Ca%703000

01+2+3+703000

DS27-1 Kidney pap clear ca

DS #DS x/yscorefindingsnoteTu/non-TuccRC/pRC

1x3y11+00TuccRC

3x5y11+00TuccRC

5x7y12+00TuccRC

7x9y11+00TuccRC

9x11y11+00TuccRC

11x13y11+00TuccRC

13x15y12+00TuccRC

15x1y21+00TuccRC

17x3y21+00TuccRC

19x5y21+00TuccRC

21x7y22+00TuccRC

23x9y2-Lost0TuccRC

25x11y22+00TuccRC

26x12y21+00TuccRC

27x13y21+00TuccRC

28x14y21+00TuccRC

29x15y2000TuccRC

30x16y21+00TuccRC

31x1y31+00TuccRC

32x2y31+00TuccRC

33x3y3000TuccRC

34x4y31+00TuccRC

35x5y31+00TuccRC

36x6y31+00TuccRC

37x7y31+00TuccRC

38x8y31+00TuccRC

39x9y3-small0TuccRC

40x10y31+00TuccRC

41x11y31+00TuccRC

42x12y31+00TuccRC

43x13y31+00TuccRC

44x14y31+00TuccRC

45x15y3000TuccRCccRC

46x16y3-small0TuccRC01+2+3+-Total

47x1y41+00TuccRCCore92741748

48x2y4000TuccRC%2266102

49x3y41+00TuccRC

50x4y4-0formalin pigTuccRC

51x5y4000TuccRC

52x6y41+00TuccRC

53x7y4-small0TuccRC

54x8y4-small0TuccRC

55x9y4000TuccRC

56x10y4000TuccRC

57x11y4000TuccRC

58x12y4000TuccRC

59x13y43+00TuccRC

60x14y4-Lost0TuccRC

61x15y42+00TupRCpRC

63x1y5000TupRC01+2+3+-Total

65x3y5000TupRCCore619127448

67x5y51+00TupRC%14432716

69x7y5000TupRC

71x9y52+00TupRC

73x11y5000TupRC

75x13y5-Lost0TupRC

77x15y51+00TupRC

79x1y62+00TupRC

81x3y6000TupRC

83x5y62+00TupRC

85x7y63+00TupRC

86x8y61+00TupRC

87x9y63+00TupRC

88x10y62+00TupRC

89x11y62+00TupRC

90x12y63+00TupRC

91x13y62+00TupRC

92x14y61+00TupRC

93x15y61+00TupRC

94x16y63+00TupRC

95x1y73+00TupRC

96x2y7-Lost0TupRC

97x3y71+00TupRC

98x4y72+00TupRC

99x5y71+00TupRC

100x6y71+00TupRC

101x7y71+00TupRC

102x8y7-Lost0TupRC

103x9y71+00TupRC

104x10y71+00TupRC

105x11y71+00TupRC

106x12y700汚いTupRC

107x13y72+00TupRC

108x14y71+00TupRC

109x15y71+00TupRC

110x16y71+00TupRC

111x1y82+00TupRC

112x2y81+00TupRC

113x3y82+00TupRC

114x4y81+00TupRC

115x5y82+00TupRC

116x6y83+0？？？TupRC

117x7y81+00TupRC

118x8y83+00TupRC01+2+3+-Total

119x9y81+00TupRCCore15461681196

120x10y8-0formalin pigTupRC%1854199

01+2+3+17.64705882352941354.11764705882352918.8235294117647079.4117647058823533

DS26-1 Uterus Endometrial ca

DS #DS x/yscorefindingsnoteTu/non-Tu

1y1/x30000

3y1/x53+000

5y1/x7-Lost00

7y1/x90000

9y1/x112+000

11y1/x132+000

13y1/x150000

15y2/x11+000

16y2/x22+000

17y2/x3-Lost00

18y2/x4-Lost00

19y2/x51+000

20y2/x61+000

21y2/x7-Lost00

22y2/x81+000

23y2/x90000

24y2/x101+000

25y2/x11-Lost00

26y2/x120000

27y2/x131+000

28y2/x142+000

29y2/x152+000

30y2/x162+000

31y3/x10000

32y3/x21+000

33y3/x30000

34y3/x42+000

35y3/x50000

36y3/x60000

37y3/x71+000

38y3/x81+000

39y3/x91+000

40y3/x10-small00

41y3/x110000

42y3/x123+000

43y3/x1300nuclear0

44y3/x142+000

45y3/x150000

46y3/x16-small00

47y4/x12+000

48y4/x2-Lost00

49y4/x30000

50y4/x40000

51y4/x53+000

52y4/x62+000

53y4/x70000

54y4/x80Lost00

55y4/x92+02 type histology0

56y4/x100000

57y4/x110000

58y4/x122+000

59y4/x130000

60y4/x140000

61y4/x151+000

62y4/x160000

63y5/x1-Lost00

64y5/x2-Lost00

65y5/x31+000

66y5/x43+000

67y5/x5-Lost00

68y5/x60000

69y5/x70000

70y5/x81+000

71y5/x90000

72y5/x100000

73y5/x11-no tumorhistology?0

74y5/x122+000

75y5/x130000

76y5/x140000

77y5/x152+000

78y5/x161+000

79y6/x11+000

80y6/x21+000

81y6/x32+000

82y6/x40000

83y6/x51+000

84y6/x60000

85y6/x70000

86y6/x82+000

87y6/x92+000

88y6/x101+000

89y6/x11-Few tumor cells00

90y6/x122+000

91y6/x130000

92y6/x14-small00

93y6/x15-no tumor00

94y6/x163+000

95y7/x1-small00

96y7/x20000

97y7/x31+00001+2+3+-Total

98y7/x40000Core36211871698

99y7/x53+000%4426229

100y7/x60000

101y7/x70000

102y7/x81+000すべて Endometrial ca

103y7/x93+000

104y7/x101+000

105y7/x110000

01+2+3+43.90243902439024725.60975609756097521.9512195121951248.536585365853659



1x3y1000Tumor

3x5y12+00Tumor

5x7y13+00Tumor

7x9y13+00Tumor

9x11y11+00Tumor

11x13y11+00Tumor

13x15y11+0ざらっとした感じTumor

15x1y21+00Tumor

17x3y23+00Tumor

19x5y21+00Tumor

21x7y23+00Tumor

23x9y22+00Tumor

25x11y21+00Tumor

27x13y21+00Tumor

29x15y23+00Tumor

31x1y31+00Tumor

33x3y31+00Tumor

35x5y32+00Tumor

36x6y33+00Tumor

37x7y32+00Tumor

38x8y32+00Tumor

39x9y32+00Tumor

40x10y3-Artifact0Tumor

41x11y32+00Tumor

42x12y33+00Tumor

43x13y32+00Tumor

44x14y33+00Tumor

45x15y32+00Tumor

46x16y33+00Tumor

47x1y42+00Tumor

48x2y42+00Tumor

49x3y41+00Tumor

50x4y41+00Tumor

51x5y43+00Tumor

52x6y41+00Tumor

53x7y42+00Tumor

54x8y4000Tumor

55x9y43+00Tumor

56x10y43+00Tumor

57x11y41+00Tumor

58x12y41+00Tumor

59x13y42+00Tumor

60x14y41+00Tumor

61x15y41+00Tumor

62x16y4-Few tumor cells0Tumor

63x1y52+00Tumor


65x3y51+00Tumor

66x4y51+00Tumor

67x5y51+00Tumor

68x6y51+00Tumorすべて Prostate Adenoca

69x7y5000Tumor

70x8y53+00Tumor

71x9y53+00Tumor

72x10y51+00Tumor

73x11y53+00Tumor

74x12y52+Cytoplasma rich0Tumor

75x13y52+00Tumor

76x14y51+00Tumor

77x15y51+00Tumor

78x16y53+00Tumor

79x1y6000Tumor

80x2y62+00Tumor

81x3y62+00Tumor

82x4y62+00Tumor

83x5y62+00Tumor01+2+3+-Total

84x6y61+00TumorCore4242116368

85x7y62+00Tumor%6373225

01+2+3+6.153846153846154236.9230769230769232.30769230769230724.615384615384617



1x3y11+00Tumor

3x5y11+00Tumor

5x7y13+00Tumor

7x9y13+00Tumor

9x11y12+00Tumor

11x13y11+00Tumor

13x15y11+00Tumor

15x1y23+00Tumor

17x3y21+00Tumor

19x5y22+00Tumor

21x7y22+00Tumor

23x9y23+00Tumor

25x11y22+Cytoplasma rich0Tumor

27x13y23+00Tumor

29x15y22+00Tumor

31x1y32+00Tumorすべて Prostate Adenoca

33x3y32+Cytoplasma0Tumor

35x5y31+00Tumor

36x6y33+00Tumor

37x7y31+00Tumor

38x8y32+00Tumor

39x9y33+00Tumor

40x10y33+00Tumor

41x11y31+00Tumor

42x12y3-00Tumor

43x13y32+00Tumor

44x14y31+00Tumor

45x15y33+00Tumor

46x16y33+00Tumor

47x1y41+00Tumor

48x2y41+00Tumor

49x3y41+00Tumor

50x4y41+00Tumor

51x5y41+00Tumor

52x6y43+00Tumor

53x7y41+00Tumor

54x8y41+00Tumor

55x9y42+00Tumor

56x10y42+00Tumor

57x11y43+00Tumor

58x12y43+00Tumor

59x13y43+00Tumor

60x14y43+00Tumor

61x15y41+00Tumor

62x16y41+00Tumor

63x1y53+00Tumor

64x2y51+00Tumor

65x3y53+00Tumor

66x4y52+00Tumor

67x5y53+0heteroTumor

68x6y52+00Tumor

69x7y52+00Tumor

70x8y52+00Tumor

71x9y53+00Tumor

72x10y53+00Tumor

73x11y52+Cytoplasma0Tumor

74x12y51+00Tumor

75x13y52+00Tumor

76x14y51+00Tumor

77x15y51+00Tumor

78x16y53+00Tumor

79x1y62+00Tumor

80x2y62+00Tumor

81x3y63+00Tumor

82x4y62+00Tumor


84x6y63+00TumorCore0222025168

85x7y63+00Tumor%0333037

01+2+3+032.83582089552238929.85074626865671737.313432835820898

DS24-2 Bladder TCC


1x3y1000Tumor

2x4y13+00Tumor

3x5y12+00Tumor

4x6y1000Tumor

5x7y11+00Tumor

6x8y13+00Tumor

7x9y13+00Tumor

8x10y13+00Tumor

9x11y13+Artifact0Tumor

10x12y13+00Tumor

11x13y11+00Tumor

12x14y11+00Tumor

13x15y11+00Tumor

14x16y13+00Tumor

15x1y21+00Tumor

16x2y21+00Tumor

17x3y22+00Tumor

18x4y23+00Tumor

19x5y21+00Tumor

20x6y23+00Tumor


22x8y23+00Tumor

23x9y23+00Tumor

24x10y23+00Tumor

25x11y21+00Tumor

26x12y2000Tumor

27x13y21+00Tumor

28x14y23+00Tumor

29x15y2000Tumor

30x16y21+00Tumor


32x2y3000Tumor

33x3y31+00Tumor

34x4y33+00Tumor

35x5y31+00Tumor

36x6y31+00Tumor


38x8y33+00Tumor

39x9y31+00Tumor

40x10y33+00Tumor

41x11y3-Lost0Tumor

42x12y33+00Tumor

43x13y3000Tumor

44x14y33+00Tumor

45x15y32+0membrane?Tumor


47x1y41+00Tumor

48x2y43+00Tumor

49x3y42+00Tumor

50x4y42+00Tumor

51x5y41+00Tumor

52x6y43+00Tumor

53x7y43+00Tumor

54x8y4-Lost0Tumor

55x9y41+00Tumor

56x10y43+00Tumor

57x11y43+00Tumor

58x12y42+00Tumor

59x13y43+00Tumor

60x14y41+00Tumor

61x15y43+00Tumor

62x16y41+00Tumor

63x1y53+00Tumor

64x2y53+00Tumor

65x3y53+00Tumor

66x4y5-no tumor0Tumor

67x5y52+00Tumor

68x6y53+00Tumor

69x7y52+00Tumor

70x8y53+00Tumor

71x9y52+00Tumor

72x10y5-no tumor0Tumor

73x11y500nuclearTumor

74x12y53+00Tumor

75x13y52+00Tumor

76x14y5000Tumor

77x15y53+00Tumor

78x16y51+00Tumor

79x1y61+00Tumor

80x2y63+00Tumor


82x4y63+00Tumor

83x5y63+00Tumor

84x6y61+small0Tumor

85x7y63+00Tumor

86x8y63+00Tumor

87x9y63+00Tumor

88x10y63+00Tumor

89x11y60Cytoplasma rich0Tumor

90x12y61+00Tumor

91x13y62+00Tumor

92x14y63+00Tumor

93x15y63+00Tumor

94x16y61+00Tumor

95x1y7000Tumor

96x2y73+00Tumor


98x4y73+00Tumor


100x6y7-00Tumor

101x7y71+00Tumor

102x8y73+00Tumor

103x9y72+00Tumor

104x10y73+00Tumor

105x11y73+00Tumor

106x12y73+00Tumor

107x13y73+00Tumor


109x15y73+00Tumor

110x16y7000Tumor


112x2y83+00TumorCore1326145312118

113x3y81+00Tumor%12251350

114x4y800HER3 posi cells scatteredTumor

115x5y83+00Tumor

116x6y8-Lost0Tumor

117x7y8000Tumorすべて Transitional cell ca

118x8y82+00Tumor

01+2+3+12.26415094339622624.52830188679245213.2075471698113250

DS23.2 Liver HCC


1x3y1-Lost0Tumor

3x5y1000Tumor

5x7y1000Tumor

7x9y11+Lost0Tumor

9x11y1000Tumor

11x13y1-00Tumor

13x15y1000Tumor

15x1y2-Lost0Tumor

17x3y2000Tumor

19x5y2000Tumor

21x7y21+00Tumor

23x9y2000Tumor

25x11y2000Tumor

27x13y21+00Tumor

29x15y21+00Tumor

31x1y3000Tumor

33x3y3000Tumor

35x5y3ERROR:#REF!0ERROR:#REF!Tumor

37x7y3000Tumor

39x9y3000Tumor

41x11y300ERROR:#REF!Tumor



47x1y41+00Tumor

49x3y4000Tumor

51x5y43+00Tumor

53x7y4000Tumor

55x9y4-Lost0Tumor

57x11y4000TumorすべてHCC

59x13y4000Tumor

61x15y4000Tumor

63x1y5000Tumor

65x3y5000Tumor

67x5y5000Tumor

69x7y5000Tumor

71x9y5000Tumor

73x11y5-Lost0Tumor

75x13y52+00Tumor

77x15y5000Tumor

79x1y61+0biliary duct +Tumor

81x3y6000Tumor

82x4y6-Lost0Tumor


84x6y6000TumorCore361111756

85x7y6000Tumor%732222

86x8y6000Tumor

87x9y6-Lost0Tumor

88x10y61+00Tumor

89x11y6000Tumor

90x12y61+00Tumor

91x13y61+00Tumor

92x14y6000Tumor

93x15y6000Tumor

94x16y6000Tumor

95x1y7000Tumor

96x2y7000Tumor

97x3y71+00Tumor

01+2+3+73.46938775510204822.4489795918367362.04081632653061232.0408163265306123

DS23.1 Liver HCC


1x3y11+00Tumor

3x5y11+00Tumor

5x7y1000Tumor

7x9y1000Tumor

challenges in developing biomarker assays for patient ......drugs –clinical and regulatory...

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