High Frequency of KRAS Mutation in Penile Squamous Cell Carcinomas.
Javier Hernandez-Losa, Claudia M Valverde, Carla Ferrandiz-Pulido, Rosa Somoza, Ines de Torres, Santiago Ramon y Cajal. Hospital University Vall d´ Hebron, Barcelona, Spain; Hospital University Vall d´Hebron, Barcelona, Spain
Background: Several risk factors have been associated with the carcinogenesis of penile squamous cell carcinomas (PSCC), most of them related to poor hygiene and HPV infections. The molecular biology of these carcinomas is not well understood, and the treatment of metastatic disease remains undefined. Recently, EGFR overexpression arises as a good molecular marker present in almost 90% of PSCC, and patients treated with EGFR directed therapies have shown promising results. The aim of this study was to analyze somatic mutations downstream of this receptor that could be activated and associated with resistance to EGFR inhibitors.
Design: We analyzed the somatic mutation of BRAF and KRAS in a total of 28 samples of PSCC including 17 usual type SCC, 10 verrucous carcinomas and 1 basaloid carcinoma. The samples were collected from de archives of the Pathology Department of our institution from 1996 to 2009. The DNAs were extracted from FFPE blocks by Biorobot EZ1 following the manufacturer protocol of the EZ1-DNA Tissue kit (Qiagen). KRAS and BRAF mutations were amplified with specific primers, and sequenced by Sanger with Bigdye terminator v3.1 Cycle Sequencing Kit
Results: No BRAF mutations were found in our series. However, we identified somatic missense mutations in the KRAS gene in 6 out of 26 penile cancer samples (23%). Two samples could not be evaluated for KRAS status. All mutants were activating G12D mutations. The histopathological characteristics of the tumors bearing KRAS mutations were studied, observing 3 out of 6 mutations in usual SCC tumours, 2 in verrocous and 1 in basaloid carcinoma. The grade of these tumors was as follows: 3 Stage III, 1 Stage II and 2 Stage I carcinomas.
Conclusions: BRAF mutations are not involved in the signalling downstream of EGFR in this type of carcinomas. KRAS mutations, in contrast, were found in 23% of PSCC analyzed. These mutations don't seem to strongly correlate to any histology type of carcinoma, although they tend to be more present in advanced stages (II and III) in comparison with earlier stages. These results suggest a role of KRAS mutation in the prognosis and progression of these carcinomas and support the importance to determine KRAS status in the selection of patients to be treated with anti-EGFR based therapies
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 91, Tuesday Afternoon