Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes

Abstract

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient's circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women's cancer.

Keywords: PIK3CA; cervical adenocarcinoma; mutation.

Figure 1

Kaplan–Meier analysis (A) Progression-free survival correlated to PIK3CA in circulating DNA collected before treatment in cervical adenocarcinoma (p = 0.0291) (hazard ratio = 7.7068). (B) Overall survival correlated to PIK3CA in circulating DNA collected before treatment in cervical adenocarcinoma (p = 0.0499) (hazard ratio = 6.6105).

Figure 2

ROC chart. (A) Survival of cervical adenocarcinoma predicted by PIK3CA mutation status as detected in circulating DNA collected before treatment. (B) Survival of cervical adenocarcinoma predicted by PIK3CA mutation status as detected in circulating DNA collected during follow-up after treatment. (C) Recurrence of cervical adenocarcinoma predicted by PIK3CA mutation status as detected in circulating DNA collected during follow-up after treatment.