the role of immunochemistry in the sdhx mutations in ... · pdf fileposter ece 2016 presented...

Poster presented at: ECE 2016 4-GP Anna Angelousi DOI: 10.3252/pso.eu.18ECE.2016 Adrenal 1 GP4 Serial number: 360 The role of immunochemistry in the SDHx mutations in pheochromocytomas and paragangliomas Angelousi A 1 , Kyriakopoulos G 2 , Konstantinou P 2 , Zografos G 3 , Piaditis G 3 , Xoreutaki T 3 , Rontogianni D 2 , Kaltsas G 1 . 1 Department of Pathophysiology, Unit of Endocrinology, Kapodistrian University of Athens , 2 Department of Pathology, Evangelismos Hospital, Athens ,Greece 3 Department of Pathology, Gennimatas Hospital, Athens , Greece Introduction: Early detection of succinate dehydrogenase complex (SDH) mutations in patients with pheochromocytoma and paragaglioma (PPC/PGL) has important implications as when present the risk of malignancy is increased. The use of negative immunohistochemical (IHC) staining for SDH subunit B, D, A (SDHB/-D/-A) has been proposed as an indicator of SDHs mutation and as an effective substitute for the high-cost genetic screening of all of these genes. Methods: We have performed SDHB/-D/-A and Ki-67% immunohistochemical staining in a series of 29 paraffin embedded PPCs/PGLs specimens. Screening for point mutations by direct Sanger sequencing was performed in germline DNA from patients with potential aggressive (PASS>6) PPC or metastatic PPCs at the initial diagnosis or in cases of PGLs. Results: Twenty-six cases with PPCs and 3 with PGLs were enrolled (18 females). Three cases were metastatic at diagnosis whereas two developed metastases during follow up. Ten cases (40%) had a PASS >6. Mean Ki-67% was 2% for cases with mutation and 2.6% for cases without mutations (p=0.8). Genetic testing for germline analysis had previously been performed in 21 cases and positive results were found in 7 cases (1 case was found positive for SDHB mutation, 1 for familial SDHD, 2 for RET, 2 for NF1 and 1 for VHL mutation) Table 1. The patient with the SDHB germinal mutation exhibited negative SDHB and positive SDHD/-A staining pattern. The patient with the SDHD germinal mutation exhibited negative SDHB/-D and positive SDHA staining pattern. Cases with RET, NF1 and VHL germline mutation as well as those without any mutations exhibited positive SDHB/-A and negative SDHD immunostaining. The patient with SDHB genetic mutation The patient with SDHD genetic mutation Discussion: Our results are in agreement with previous series which have shown that SDHB/-D/-A immunohistochemical analysis could be a low cost technique to predict the presence of SDHx mutations. SDHB immunochemistry when used as a guide to genetic testing could potentionaly reduce the effort, time and costs of testing among patients with PPC/PGLs. Bibliography: Castelblanco E, Endocr Pathol , 2013; Menara M, JCEM, 2015 SDHD immunostaining SDHA immunostaining SDHB immunostaining SDHD immunostaining SDHΑ immunostaining SDHB immunostaining

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Page 1: The role of immunochemistry in the SDHx mutations in ... · PDF filePoster ECE 2016 presented at: 4-GP Anna Angelousi DOI: 10.3252/pso.eu.18ECE.2016 ... (SDH) mutations in patients

Poster presented at:

ECE

2016 4-GP

Anna Angelousi DOI: 10.3252/pso.eu.18ECE.2016

Adrenal 1

GP4Serial number: 360

The role of immunochemistry in the SDHx mutations in pheochromocytomas and paragangliomasAngelousi A1, Kyriakopoulos G2, Konstantinou P2, Zografos G3 , Piaditis G3, Xoreutaki T3,Rontogianni D2, Kaltsas G1.

1 Department of Pathophysiology, Unit of Endocrinology, Kapodistrian University of Athens , 2 Department of Pathology, Evangelismos Hospital, Athens ,Greece 3 Department of Pathology, Gennimatas Hospital, Athens , Greece

Introduction: Early detection of succinate dehydrogenase complex (SDH) mutations in patients with pheochromocytoma and paragaglioma (PPC/PGL) has important implications as when present the risk of malignancy is increased. The use of negative immunohistochemical (IHC) staining for SDH subunit B, D, A (SDHB/-D/-A) has been proposed as an indicator of SDHs mutation and as an effective substitute for the high-cost genetic screening of all of these genes. Methods: We have performed SDHB/-D/-A and Ki-67% immunohistochemical staining in a series of 29 paraffin embedded PPCs/PGLs specimens. Screening for point mutations by direct Sanger sequencing was performed in germline DNA from patients with potential aggressive (PASS>6) PPC or metastatic PPCs at the initial diagnosis or in cases of PGLs. Results: Twenty-six cases with PPCs and 3 with PGLs were enrolled (18 females). Three cases were metastatic at diagnosis whereas two developed metastases during follow up. Ten cases (40%) had a PASS >6. Mean Ki-67% was 2% for cases with mutation and 2.6% for cases without mutations (p=0.8). Genetic testing for germline analysis had previously been performed in 21 cases and positive results were found in 7 cases (1 case was found positive for SDHB mutation, 1 for familial SDHD, 2 forRET, 2 for NF1 and 1 for VHL mutation) Table 1. The patient with the SDHB germinal mutation exhibited negative SDHB and positive SDHD/-A staining pattern. The patient with the SDHD germinal mutation exhibited negative SDHB/-D and positive SDHA staining pattern. Cases with RET, NF1 and VHL germline mutation as well as those without any mutations exhibited positive SDHB/-A and negative SDHD immunostaining.

The patient with SDHB genetic mutation

The patient with SDHD genetic mutation

Discussion: Our results are in agreement with previous series which have shown that SDHB/-D/-A immunohistochemicalanalysis could be a low cost technique to predict the presence of SDHx mutations. SDHB immunochemistry when used as a guide to genetic testing could potentionaly reduce the effort, time and costs of testing among patients with PPC/PGLs.Bibliography: Castelblanco E, Endocr Pathol , 2013; Menara M, JCEM, 2015

SDHD immunostaining SDHA immunostaining

SDHB immunostaining SDHD immunostaining SDHΑ immunostaining

SDHB immunostaining

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