Clinicopathological and biological analysis of mutation and amplification in cervical carcinomas.

The aim of the present study was to evaluate the mutation and amplification status of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α () gene, as well as the association with clinicopathological characteristics and prognosis, in Japanese patients with cervical cancer. Fluorescence hybridization and polymerase chain reaction were performed to assess gene amplification and mutation. The inhibitors temsirolimus and NVP-BEZ235 were used to inactivate the phosphatidylinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin kinase (mTOR) pathway to clarify the roles of PI3K/AKT activation in cervical carcinoma cells harboring associated mutations. Four somatic point mutations (4/71, 5.6%) were found in exon 20 in cervical squamous cell carcinoma samples, whereas three (3/53, 5.7%) were found in exon 9 in cervical adeno/adenosquamous cell carcinoma samples. Amplification of was also observed in this study and amplification was more commonly found in adeno/adenosquamous carcinomas than in cervical squamous cell carcinomas (20.7 vs. 1.4%, respectively, P=0.0003). No significant correlation was obesrved between amplification and progression free survival (P=0.7576) or overall survival (P=0.8859). Moreover, no association between mutation and sensitivity to PI3K/AKT/mTOR inhibitors was observed in cervical carcinoma cells. These results suggest that in Japanese patients with cervical cancer, mutation and amplification cannot act as biomarkers for individualized molecular targeted therapy.