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

Abstract

Summary 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.

Value of Forkhead Box A1 (FOX A1) Immunohistochemical Expression in Epithelial Ovarian Carcinoma

“…FOX A1 expression was significantly correlated with tumor), bilaterality (P > 0.001), in this work .This results agreed with Elnashar et al (22) , Wang et al (13) , and disagreed with Sheta et al (8) they reported that although there was a propensity for unilateral tumors to express more FOXA1 than bilateral ones, this difference did not achieve statistical significance.…”

“…Regarding tumor metastasis we found lymph node metastasis in (32.6%) of cases , and omental deposits in (32.6%)of cases, this was nearer to that found by Sheta et al (8) . regarding lymph node metastasis (24.5%) , while omental deposits was higher (63.3%) .…”

“…This finding was similar to that of Wang et al (13) who noted that 46.4% of tumors were bilateral. However other studies found that bilaterality of tumors were predominant (22) , while Sheta et al (8) found that unilateral was the predominant .…”

“…Sheta et al (8) reported that the mean age of the patients was 57.1. Abouhashem et al (16) found that the mean age of patients was 58.7 ±6.2 years.…”

“…Hepatocyte nuclear factor 3 α(/HNF3α), also known as forkhead box A1, is a gene that is encoded by FOX on human chromosome 14q21.1 (8) . The transcription factor FOX A1, which is widely expressed and involved in the expression of multiple crucial genes during the development of various types of human tissue for the growth of various tissues, including the liver, lungs, midbrain, and mammary glands.…”