Prevalence of APC and PTEN Alterations in Urachal Cancer
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ORIGINAL ARTICLE
Prevalence of APC and PTEN Alterations in Urachal Cancer Nikolett Nagy 1 & Henning Reis 2 & Boris Hadaschik 3 & Christian Niedworok 3 & Orsolya Módos 1 & Attila Szendrői 1 & Krisztina Bíró 4 & Thomas Hager 2 & Thomas Herold 2 & Jason Ablat 5 & Peter C. Black 5 & Krzysztof Okon 6 & Yuri Tolkach 7 & Anita Csizmarik 1 & Csilla Oláh 1 & David Keresztes 1 & Felix Bremmer 8 & Nadine T. Gaisa 9 & Joerg Kriegsmann 10 & Ilona Kovalszky 11 & András Kiss 12 & József Tímár 12 & Marcell A. Szász 13 & Michael Rink 14 & Margit Fisch 14 & Péter Nyirády 1 & Tibor Szarvas 1,3 Received: 2 March 2020 / Accepted: 7 July 2020 # The Author(s) 2020
Abstract Urachal carcinoma (UrC) is a rare tumor with remarkable histological and molecular similarities to colorectal cancer (CRC). Adenomatous polyposis coli (APC) is the most frequently affected gene in CRC, but the prevalence and significance of its alterations in UrC is poorly understood. In addition, loss of phosphatase and tensin homologue (PTEN) was shown to be associated with therapy resistance in CRC. Our primary aim was to assess specific genetic alterations including APC and PTEN in a large series of UrC samples in order to identify clinically significant genomic alterations. We analyzed a total of 40 UrC cases. Targeted 5-gene (APC, PTEN, DICER1, PRKAR1A, TSHR, WRN) panel sequencing was performed on the Illumina MiSeq platform (n = 34). In addition, ß-catenin (n = 38) and PTEN (n = 30) expressions were assessed by immunohistochemistry. APC and PTEN genes were affected in 15% (5/34) and 6% (2/34) of cases. Two of five APC alterations (p.Y1075*, p.K1199*) were truncating pathogenic mutations. One of the two PTEN variants was a pathogenic frameshift insertion (p.C211fs). In 29% (11/38) of samples, at least some weak nuclear ß-catenin immunostaining was detected and PTEN loss was observed in 20% (6/30) of samples. The low prevalence of APC mutations in UrC represents a characteristic difference to CRC. Based on APC and ß-catenin results, the Wnt pathway seems to be rarely affected in UrC. Considering the formerly described involvement of PTEN protein loss in anti-EGFR therapy-resistance its immunohistochemical testing may have therapeutic relevance. Keywords Urachal cancer . Colorectal cancer . Molecular genetics . Mutation . APC . ß-catenin
* Tibor Szarvas [email protected]
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Institute of Pathology, University of Göttingen, 37073 Göttingen, Germany
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Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany
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Department of Urology, Semmelweis University, Budapest 1082, Hungary
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Institute of Pathology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany
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Cytology and Molecular Diagnostics Trier, Center for Histology, 54296 Trier, Germany
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Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany
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1st Institute of Pathology and Expreimental Cancer Research, Semmelweis University, Budapest 1085, Hungary
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2nd De
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