FOXA1 expression and its association with mucin expression and KRAS mutation in ovarian mucinous tumors: implications for tumor progression and differentiation.

This study aimed to investigate forkhead box A1 (FOXA1) expression in ovarian mucinous tumors and its association with mucin expression and KRAS mutation status to clarify its role in tumor progression and differentiation. We analyzed 57 normal tissues or benign ovarian lesions, 110 mucinous ovarian tumors, including mucinous carcinomas, and 214 other ovarian epithelial carcinomas using immunohistochemistry for FOXA1, MUC2, MUC5AC, and MUC6. We also performed KRAS mutation analysis. Strong nuclear staining of FOXA1 was observed in Walthard nests, Brenner tumors, and fallopian tube ciliated epithelium. FOXA1 expression was significantly associated with mucinous histology in ovarian epithelial carcinomas (P < 0.001). In mucinous tumors, FOXA1 was expressed in 73.6% of cystadenomas, 91.4% of borderline tumors, 100% of borderline tumors with intraepithelial carcinomas, and 87.5% of carcinomas. MUC2 expression progressively increased from mucinous cystadenomas to borderline tumors (P < 0.050) and significantly correlated with FOXA1 expression (P = 0.024). The prevalence of KRAS mutations also tended to increase with the malignancy of mucinous tumors (P < 0.050); however, KRAS mutations were significantly enriched in FOXA1-negative cystadenomas compared with FOXA1-positive cystadenomas (P < 0.050). A stepwise increase was noted in the percentage of both KRAS mutations and FOXA1 expression from cystadenoma to carcinoma. Mucinous ovarian tumors commonly express FOXA1. The co-occurrence of KRAS mutations and FOXA1 expression may be important for driving the progression and intestinal differentiation of mucinous ovarian tumors.