High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer

Abstract

Background: Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC).

Aim: This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient's outcome.

Methods: Patient's socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis.

Results: FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor's anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor's anatomical extent and tumor's size (p ≤ 0.001, = 0.046 and = 0.023 respectively).

Conclusion: FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

Keywords: FOXA1; clinico-pathological; epithelial ovarian cancer; immunohistochemistry; survival.