Relating Pik3ca Mutation Status With Clinicopathologic Factors And Outcome In Patients With Cervical Cancer Treated With Primary Surgery With Or Without Post-Operative Adjuvant Chemoradiotherapy

PIK3CA somatic mutation has been associated with worse survival outcomes in cervical cancer treated with primary chemoradiotherapy. In patients treated with primary surgery, outcomes are less well defined as adjuvant treatment is often administered but not well annotated. This study hypothesized that patients harboring PIK3CA mutated tumors would have more advanced disease on post-operative specimens and this would correlate to worse survival outcomes. With institutional ethics approval, 291 patients with a diagnosis of cervical cancer treated with primary surgical management between 2000 and 2015 were retrospectively identified. A database containing all clinical data for these patients was then populated. FFPE specimens were obtained and next generation sequencing used to identify tumor mutations. In brief, tumor DNA was extracted and assayed for SNPs and Indels in 50 oncogene and tumor suppressor genes using the Ampliseq Cancer Hot Spot Panel v2 (CHPv2) on the Ion PGM instrument using a 316v2 chip. Bioinformatic analysis was performed using Torrent Suite Software version 5.05. All variants were manually reviewed using a high-performance visualization tool. Descriptive statistics were used to characterize the data. 180 tumors had sufficient specimens to undergo sequencing. On PI3K pathway analysis, 37 (21%) tumors harbored PIK3CA, 8 (4%) harbored FBXW7, 4 (2%) harbored PTEN and 3 (2%) harbored AKT mutations. In comparison of PIK3CA mutant and wildtype tumors no differences were found in patient age [48 (40-57) vs 44 (38-54); p = 0.233]; proportion of patients with pathologic FIGO stage I disease [30 (81%) vs 131 (92%); p = 0.075]; proportion with squamous histology [28 (76%) vs 90 (63%); p = 0.176]; proportion with grade 3 disease [10 (39%) vs 44 (42%); p = 0.817]; proportion with LVSI [24 (65%) vs 79 (55%); p = 0.224]; p16 positivity [33 (94%) vs 112 (90%); p0.526]; or final depth of cervical stromal invasion [8 (5-13)mm vs 8 (5-13)mm; p = 0.906]. PIK3CA mutation was associated with pathologically positive lymph nodes [11 (30%) vs 23 (16%); p = 0.035; correlation coefficient: -0.172 (p = 0.021)] and correspondingly, indications for post-operative chemoradiotherapy [17 (46%) vs 33 (23%); p = 0.008]. There was no correlation between PIK3CA mutation status and Kaplan-Meier estimated overall (5-year: 87% vs 79%; Log-Rank p = 0.29] or progression free [5-year: 81% vs 74%; Log-Rank p = 0.35] survival. On multivariate analysis, PIK3CA mutation was not significantly associated with overall survival [HR: 0.4 (0.2-1.2); p = 0.103] or progression free survival [HR: 0.5 (0.2-1.2); p = 0.151]. PIK3CA mutation corresponded with increased nodal burden on post-operative pathology and need for adjuvant chemoradiotherapy. The lack of correlation with survival outcomes, is intriguing and warrants further investigation.