Trefoil factor family 3 (TFF3) expression and its interaction with estrogen receptor (ER) in endometrial adenocarcinoma

Objectives TFF3 has been found to be up-regulated at the gene and protein levels in endometrioid adenocarcinoma (EAC) when compared to uterine serous carcinoma (USC) and normal endometrium. In addition, TFF3 has been proven to be an estrogen-responsive gene and its expression level positively correlated to estrogen-receptor (ER) status in breast cancer cell culture. The aims of this study are to determine the expression and the prognostic value of TFF3 in a large series of human endometrial cancer and its relation with ER. Methods We evaluated 328 endometrial carcinomas using TFF3 and ER antibody on paraffin-embedded tissue. 74% were type I (EAC), and 26% were type II (USC, CCC and carcinosarcoma). Results In type I carcinomas, TFF3⁺ expression was associated with no lympho-vascular invasion (p = 0.0131), disease status (p = 0.0132), recurrence-free survival (p = 0.0424) and overall survival (p = 0.0018). There was a positive association between TFF3 and ER (p <.0001). The combination of TFF3⁺/ER⁺ was associated with low FIGO grade (p =.0122), early FIGO stage (p =.0062), absence of recurrence (p =.0037), absence of LVI (p =.0011), no lymph node involvement (p =.0116) and disease status (p =.0107). TFF3 appeared to be an independent prognostic marker in predicting recurrences (p =.046). In type II carcinomas, TFF3 failed to have a prognostic value. Conclusion 1-TFF3 seems to be a novel pathway in the pathogenesis of type I endometrial carcinomas. 2-The strong association of TFF3 and ER in the estrogen-dependent endometrioid carcinoma could explain the reason for its frequent expression by this tumor type. 3-TFF3⁺ seems to forecast a good prognosis in type I endometrial carcinomas. Based on our data, TFF3 expression in endometrial cancer deserves further investigation.