Introduction

The phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) gene is mutated and amplified in various cancers leading to dysregulation of the PI3K-AKT-mTOR pathway, which is known to regulate cell proliferation and survival. Nobody to our knowledge has evaluated PIK3CA copy number status (CNS) in penile cancer (PC). We aimed to determine the prevalence of PIK3CA copy number gain, its effect on PIK3CA mRNA expression and activation of the PI3K-AKT-mTOR pathway in PC.

Materials and Methods

Fresh frozen tissue specimens and paraffin embedded blocks were obtained from 24 primary penile cancer patients with additional 15 corresponding paired normal epithelial tissue. PIK3CA gene CNS and mRNA were examined using fluorescence in-situ hybridisation (FISH) and Quantitative Real Time PCR, respectively. Phospho-AKT (p-AKT) and phospho-mTOR (p-mTOR) protein expression were assessed using western blot.

Results

PIK3CA copy number gain was found in 11/23 (48%) patients. Penile tumours showed significantly lower expression of PIK3CA mRNA (3.8±2.9 vs 7.4±2.2, P=0.0004), p-AKT (0.3±0.3 vs 1.0±0.7, P=0.0008) and p-mTOR (0.3±0.2 vs 0.7±0.5, P=0.0033) than normal adjacent penile tissue. No association was found between PIK3CA CNS and expression of PIK3CA mRNA, p-AKT or p-mTOR protein. (P=0.4779, P=0.894 and P=0.5095, respectively).

Conclusion

A high frequency of PIK3CA copy number gain was found in PC, suggesting that the PI3K pathway may play a role in penile carcinogenesis. However, surprisingly, we found no association between PIK3CA CNS and PIK3CA mRNA, p-AKT or p-mTOR protein expression. Further work to clarify the link between PIK3CA CNS and activation of the PI3K pathway is needed.