The Prognostic Value of PIK3CA Copy Number Gain in Penile Cancer

Abstract

ObjectiveTo determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain in penile cancer has prognostic value and association with histopathological parameters, human papillomavirus (HPV), and clinical outcome. MethodsPIK3CA copy number status was assessed with fluorescence in situ hybridization in tissue microarrays generated from archival paraffin embedded blocks of 199 patients with primary penile squamous cell carcinoma (PSCC). HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 174 patients. PIK3CA copy number status was correlated with histopathological parameters, high-risk HPV, cancer-specific survival and time to recurrence. ResultsPIK3CA copy number gain was found in 84/199 (42%) of penile cancer cases. PIK3CA copy number gain was associated with tumor subtype, grade, and stage (P = .0028, P < .0001, and P = .0397, respectively), but not with lymph node status (P = .2902). PIK3CA copy number gain showed a tendency to associate with cancer-specific survival (HR = 1.76, 95% CI; 0.94-3.3; P = .0753). In multivariate analysis, PIK3CA copy number gain was found to have no prognostic value for cancer-specific survival (P = .677). Only lymph node metastasis, high tumor grade and stage were found to be independent prognostic factors for cancer-specific survival. ConclusionPIK3CA copy number gain could be used as a marker of high-risk disease as it correlates with more aggressive PSCC histological subtypes and higher tumor grade and stage. However, it shows no significant association with lymph node metastasis or prognostic value for cancer-specific survival in PSCC.