Trefoil Factor 3 (TFF3) Is an Independent Biomarker for Better Prognosis in Endometrial Endometrioid Adenocarcinoma but Not in Uterine Serous Carcinoma
Damanzoopinder K Samrao, Dan Wang, Paulette Mhawech-Fauceglia. LAC+USC, Los Angeles, CA; Roswell Park Cancer Institute, Buffalo, NY
Background: Previously, using the Illumina Human HT-12v3.0 gene expression array we found the trefoil factor family 3 (TFF3) gene to be differentially expressed in high grade endometrioid adenocarcinoma (EAC) of the endometrium in comparison to uterine serous carcinoma (USC). We subsequently confirmed and validated this using quantitative RT-PCR. TFF3 is one of 3 members of the trefoil factor family of proteins that typically contribute to a barrier coating the surface of epithelial cells. However, their role in cancer biology is still unclear. The aims of this study were to evaluate the expression and prognostic value of TFF3 in endometrial cancer (EC).
Design: A tissue microarray of 328 EC cases was developed and stained with TFF3 monoclonal antibody. To test the association of TFF3 expression with histological and clinical parameters (age, tumor subtype, myometrial invasion, FIGO grade and stage, lymph node status, lymphovascular invasion (LVI), and disease status at last visit) Fisher's exact test was performed. Univariate and multivariate Cox regression analysis were used to determine the association between TFF3 and overall survival (OS) and recurrence free survival (RFS).
Results: Type I carcinoma accounted for 74% of cases and type II 26%, 66.5% were stage I +II and 33.5% were stage III+IV. TFF3 was positive in 60% of all cases. In univariate Cox regression analysis, TFF3 was associated with tumor grade (p <0.0001), tumor stage (p 0.0008), LVI (p 0.018), tumor subtype (p<0.0001) and disease status (p 0.0097). The 5 year OS was 55.8% for TFF3- EAC cases and 83.3% for TFF3+cases (p=0.04). The 5 year RFS was 62.3% for TFF3- EAC cases and 85.4% for TFF3+ (p 0.053). Furthermore, multivariate Cox regression analysis revealed TFF3 to be an independent predictive factor for RFS and OS in EAC but it had no value in USC.
Conclusions: 1- TFF3+ was associated with EAC subtype and with early stage disease. 2-TFF3 was an independent marker for better prognosis in EAC and it could be of use in patient management, i.e. patients with tumors expressing TFF3 may require less surveillance and follow-up. 3- We speculate that TFF3 may play a role as a tumor suppressor gene in EAC. Our results are novel and more mechanistic studies of TFF3 in the endometrial cancer are needed.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 120, Tuesday Morning