W1358

Determination of Biologic Behavior of Gastrointestinal Tract Stromal Tumors with lmmunohistochemical Methods Konstanrinos H Katsanos, Georgia Glousriarmu, Elli loachim, Dimimos Christodoulou, Michail Economou, Niki Agnantis, Epameinondas Tsianos

A/M: (iastrointestinal stromal tumors (GISTS) represent an heterogeneous group of neoplasms with usually a non predictable biologic behavior The criteria of malignancy of these tumors (GISTS) include tumor size, number of mitoses per power fieId, presence of atypia and necrosis mucosa inldtration, peiomorpbisrn and cellularity GISTS are expressing the kit receptor (c-k~t), a tyrosine kinase receptor w'inch is coded by the c-kit protooncogene, in addition, they usually express CD 117 and CD34 antigens while, in rare cases they may be also positive tur SMA (smooth muscle antigen) desmin/HHF-35 (lean musck antigen), 3- 100 prolein (neural tissue) molecules or they may be negative to all the above antigens.The aim of the study was the determination of the biologic behavior of GISTS with immunohisto- chemistry MATERIA1.S METHODS: Using the stmpravidin-viotin method (Dako) 52 GISTS (biopsy specimens or surgically removed segments) diagnosed during the last decade in our hospital were immunohistochemmically studied tot the antigen c-kit (CD117), CD34, S},s desmin and S-100 ant gens In addinon p53 and ki-67 expression was studied in order to deternrine tumor biological behavmr Sta isrical analysis was pedbrmed using the SPPS work- ing package RESULTS: From h e total number ot mesenchymal tunmrs studied based on na:>rphology and ir.arnunohistochemist U, 474% of GISTS were benign and 526% were malignant There was a statistically significant cormlatinn of GISTS malignant behawor veith p53 arid ki-67 in~munostainmg ( p = 0 0 0 1 6 and p = 0 0 0 3 respectively). No statistically signtficam correlation of ck i t (CDl17) antigen, CD68, CDIO, CD99 and SMA with p53 and ki-67 was {bund CONCLUSIONS: GISTS represent tumors with a more less undefined biological beha,nor lmmunohistochemist U studies in these tumors mainly using p53 and ki-67 immcmostaining can assist diagnosis and prognosis The p53 and k>57 immunohisto- chemist~" has a high potential ofdetemfination of malignant or benign behavior and prognosis of the~ rare gastrointestinal tumors

W1359

The Relationship Between Cyciooxygenase-2 Expression and Survival in Chemotherapy Treated Colorectal Cancer Patients Christopher Steele Katherine Sheehart, Frank Murray

introduction: There is a large body of evidence botlh m vivo and in vltm to link the inducible form ot cycloxygenase. COX-2 to colorectal carcinoma, Previous work has shown that high COX-2 levels correlates with poor survival and metastatic disease. The role of COX-2 in chemotherapy treated patients has uot been delineated, The objective of th~s study was to investigate COX-2 and survival in patients who have been treated with chemotherapy, Methods: One hundred and twenty unselected patients in whom a diagmosis of colorectaI cancer was made were included in the study, Archival tumour tissue was analysed by immunohistochemistry for COX-2. Sections were graded based on the extent of epithelial COX-2 expression. Univariate analysis was perfiarmed to assess the relationship between turnout COX-2 expression and surv~;val. Results: Forty4our cases were diagnosed as Dukes B, 64 Dukes C and i2 Dukes D. Cyclooxgyenase-2 expressed to varying extents in all cases examined. COX-2 was expressed in tumour epithelial cells, macmphages, fibroblasts and endothehal cells. Surprisingly, in this cohort of chemotherapy treated patients, a higher extent of COX-2 was associated with intproved survival (p = 0 02). When individual Dukes stage was assessed, the significant association was strongest in the Dukes B group (p = 0.08) Conclusion In this study over expression of COX-2 in chemotherapy treated patients was associated with improved survival. This is in contrast to previous studies that negatively associated COX-2 with survva/ This raises the possibihty that NSAIDs and aspirin in coElunction with chemotherapy warrants caution and further studies in larger numbers are encouraged

W1360

Follow-Up Evaluation of Dukes Bc Stage Patients for The Presence of Circulating Tumour Cells by Magnetic Cell Isolation, Real Time Quantitative Rt- Per and Serum Tumormarkers Bela Molnar, Femnc Sipos, Agues Ruzsovtcs Lalos Floro, Lydia Sreter, Zsoh Tulassay

Background: Cimulating namor ceils were found to appear in clusters and in different numbers in the peripheral blood of colorectal cancer patients by magnetic cell isolation techniques Data is missing about their time change in tbe course of and after the adjuvant chemotherapy Comparison was made to newly appaered quantitatn,-e real-time RT-PCR and traditional tumormarkers.Emphasis was placed on changes in and after the course of adjuvant chemotherapy Mate~lals and Methods: 20 rnl blood of 4 Dukes B and 5 Dukes C stage patients were drawn befure the regular adjuvant chemotherapy (Mayo protocoll) each month once and after the closure of the chemotherapy The mean tbllow-up time is 12.4+6.2 monthes alter the start of the adjuvant chemotherapy. Cimulatmg tumor cell and cell clusters were isolated with the Carcinorna enrichement Kit ( MfltenyiBiotec, BergischGladbach. Gemrany) After Ficoll paque centriib, gation, the sera was saved fur CA19-9 determinations (Elecsys, Roche, Germany) Serum c)~okemtm content was also determined by TPA ( tissue polypeptid antigen, Byk Gulden) assay The density centrifugation enriched cell pellet was lysed and the mRNA content was isolated. The mRNA was used fbr CK20 real time RT- PCR quantification (Light Cycler CK20 Quantification Kit, Roche, Germany). The quantifica- tion was done using the PBGD housekeeping gene. Ck20 RNA showed significant correlation to cimula ing tumor absoiut number (A19-9 showed correlation to TPA, cluster number and epithelial cell TPA showed negative but non-significant correlation to circulating epithe- lial cell number and single cell number Conclusions: The magnetic circulating tumor cell isolation is a usef?al method lot the evaluation of changes in the peripheral blood tumor content. 'llle clinical significance of these data needs longer follow-up nine and comparison ,a~th macroscopic and clinical data

Resulls: Status in adjuvant TPA CA19.9 CK20 RNA CirculaUng chemotherapy tumor cell

number In 57.9_-*449 12.9+9.0 5320.7_+5172" 3,~24.8" After 39+9,5 14,7• 24099+23372' 37.1-44,4"

Sta~s in Single cells Doublets Cluster Largest Epithelial Lymphocyt adjuvant Numbs" cluster cells in es in chemothera duster cluster PY In 2,~5~3,16" 0.252-,,0.8" 0.12_+04' 0,31+1.2" 0,~1.6" 0,3i• After 19.~34,1' .9,5.+27.3* 2.66.+3,9* 2,7~3,8' 10,,~17,3" 5,7~8,1"

W1361

A Survey of Small Bowel Tumours Presenting to a District General Hospital in the UK Acbuth H, Shenoy

Aim: To study the chnical features and outcomes of small bowd turnouts (SBT) presenting to a district general hospital serving apopulation ot 160,000 m the Northwest of Er@and. Methods: From Jan 1994- Dec 2001, 36 cases of SBT were identified from pathology database. Cases were excluded if the small bowd lesion was byperplastic or if it w~ts due to spread of malignancy of an adjacent organ Results: Mean age was 68.1 years (range 32-91). Majority were females (61.1%). 34 were Caucasians and 2 were Asians. 29% were asymptomatic, 26% had iron deficiency anaemia (1DA), 11% pain abdomen, l 1% obstmcuve jaundice, 4% vomiting, 4% haerrmtemesis and 4% mass. None had coeliac disease or inflammato U bowd disease. One had Fmmlial Adenomatous PoIyposis Colt. 60% were diagnosed at gastmscopy, 13% at laparotomy, 10% on ERCP, 10% on contrast stud), and 7% on uhrasound. The small bowel lesions included 6 Non-neoplastic Iesions (2 Bmnners gland hamartoma, 2 Gastric heterotropia, 1 myoepitheliaI hamartoma and 1 Hetemtrophic pancreas); 11 Bengn primary turnouts (7 Adenoma, 2 lipoma, 1 carcinoid and 1 Angiofibrolipoma); 3 Second q malig~tancies (2 from past colon cancer and 1 from choroid melanoma) and 16 puma U m&gnancies. Primary malignancies were Adenocaminoma 10 (63%), Lymphoma 2 (113%), carcinoid 2 (13%), Gastrointestinal stromal turnout I and smail ceil carcinona 1 Site of mmour m 16 cases were- duodenum (9), Ileum (4), Jejunum (3) and duodeno-jejunal flexure ( ] ) 15 patients had tmnonr at single site Symptoms included weight loss (22%), pain abdomen (21%), obstructive jaundice (16%), IDA (16%), abdominal mass (16%) and vominng (7%) It took a meart of 24.8 weeks (range 1-156) to achieve the diagnosis t?com the onset of symptoms and a mean time of 7.8 weeks (range 1-28) from presentation to diagnosis 8 had [aparotomy 7 had resection (6 complete and 1 partmI) and 1 was inoperable There ,,,,'ere 3 pert-operative deaths Lymphoma cases had chemotherapy. Among the 5 survivors, all of who had complete t~sections, 3 had recurrences in 6 8 and 60 months each. 1 patient was lost fbr follow-up Mean fbllow up in the remaining 15 was 13.2 months (range 1-72) out of whom 12 died Mean time from symptom to death was 79 months (range 1-18). Discussion: Due to rarity the dia~'~osis of SBT is achieved often too late and hence the prognosis is poor. Clinicians should have a h@r degree of suspicion in patients presenting with symptoms including IDA, weight loss or pain abdomen arid other investigations are normaI.

W1362

Stage of Presentation and Prognosis of Colon Cancer in Immigrant Chinese: Experience of a New York City Community Hospital Frederick Butler, Bart A. Kunnner

Recent immigrants to the USA form groups in which disease prevalence, recognition, treat~ ment and outcome may vary from nonqmmigrant g roups NYU Downtown Hospital (N~%;DH), at the Southenr edge of NY City's Chinatown, serves the >50,600 Chinese immigrants who reside there. We perfbrmed a retrospective analysis of Tumor Registry data on stage at presentation and sur,Aval for all Chinese patients in whom colon cancer was diagnosed at NYUDH from 1994-8 and in Whom staging was possible. Staging was determined by the American Joint Committee on Cancer criteria. We compared this to data from the National Cancer Institute Smveillance, Epi&miology and End Results Program (SEER). 214 patients were staged during this interval. For NYUDH patients the stage of presentation mode was 3 compared to stage 2 Ihr the overall USA SEER data. The mean 5-year s~arvival tbr stage 3 NYUDH patients was 64.7% compared to 644% fur SEER The mean 5-year survival for all staged NYUDH colon cancer patients was 47% compared to 61.1% for SEER Conclusion: Immigrant Chinese patients in New York CW's Chinatown who undergo surge U for colon cancer present with more advanced &sense and have a poorer overall outcome than the average American.

Colon Cancer, Mode Stage of Presentation]Age at Presentation/5 year sur~ivel

NYUDH US Most Common Stage at Presentation (AJCC) 3 2 Age at Presentation (years) 60-79 70-79 Overall 5 year survival (%) 47 61.1

A - 6 5 5 A G A A b s t r a c t s