PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy

ObjectiveMutational activation of PIK3CA is associated with poor prognosis in patients with solid tumors, and may predict favorable response to PI3K/AKT/mTOR pathway inhibitors. However, PIK3CA mutational status has not previously been evaluated in patients with cervical carcinoma treated with radical chemoradiotherapy (CRT). The aims of this study were (1) to evaluate the frequency of PIK3CA mutations in patients with cervical cancer treated with radical CRT and (2) to examine the effect of tumor PIK3CA mutational status in pre-treatment biopsies on overall survival (OS) and progression-free survival (PFS).MethodsPatients with cervical cancer, treated at a single institution with radical CRT, from 1999 to 2008, were eligible for this retrospective study. Pre-treatment tumor biopsies (n = 157) were retrieved. Genomic DNA was extracted from tumor blocks, and exons 9 and 20 of the PIK3CA gene were sequenced for mutations.ResultsEighty-two tumors were sequenced for both exon 9 and exon 20. 19/82 (23%) tumors were PIK3CA mutation positive; of these 84% were squamous cell carcinomas. 79% of mutations were in exon 9. PIK3CA mutation status was strongly associated with overall survival (OS) in FIGO stage IB/II patients, unadjusted HR 6.0 (95% CI 2.1–17.5), p = 0.0002, but not stage III/IVA patients, unadjusted HR 1.0 (95% CI 0.32–3.1), p = 0.98.ConclusionsIn cervical cancer patients treated with CRT, tumor PIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers. Further evaluation with a larger dataset will be required to validate these findings to inform potential clinical trials designs involving PI3K/AKT/mTOR pathway inhibitors.

► PIK3CA mutation status was evaluated in locally advanced cervical cancer patients treated with radical chemoradiotherapy
► PIK3CA mutations were found in 23% of evaluable patient tumors
► Overall survival effect in FIGO stage I/II patients with PIK3CA mutant tumors is worse, compared to stage III/IV patients