Prevalence and Prognostic Significance of PIK3CAMutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CAand associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CAcopy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations—the majority (n=37, 77.1%) PIK3CAmutations. PIK3CAmutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P=0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P=0.004]. On multivariable analysis, PIK3CAstatus was not associated with overall survival (P=0.103) or progression-free survival (P=0.240) at 5 yrs, nor was PIK3CAcopy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17–0.89; P=0.025)] but not overall survival (P=0.087). The correlation of PIK3CAwith pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CAassessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.