TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary

Abstract

Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P < 0.001) suggesting a potential function of the protein in that subtypes. Associations of TFF3 expression with FIGO stage and micropapillary pattern were significant in the overall cohort but confounded by their correlation with histological subtypes. The highly specific expression of TFF3 in MBOT may help to further clarify potential relationships of tumors with mucinous histology and warrants further studies.

Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

“…El-Balat et al analyzed the expression of TFF3 in a cohort of 137 borderline tumors of the ovary (BOT): none of the serous and endometrioid BOT showed strong TFF3 expression. On the contrary, a higher TFF3 expression was found in BOT mucinous histology and BOT with mixed histology, suggesting a potential function of the protein in these histological subtypes [37]. Expression analysis of TFF3 was performed in a cohort of 91 OC patients by Hoellen et al No significant difference in TFF3 expression was found based on age, FIGO stage or residual tumor; meanwhile, a significant correlation of TFF3 expression and grade was detected [48].…”

“…Many authors have employed array-based genome-wide discovery platforms to identify aberrant mRNA expression and somatically acquired DNA sequence variants or mutations to determine the molecular changes underlying the development of OC and EC as a first step to identify molecular markers with potential clinical utility [33,34]. Using this technology, some proteins such as TFF3, Romo-1, NF-кB and SFRP4 have been identified as potential for diagnostic and prognostic targets in EC and OC [18,[35][36][37][38].…”

“…These results seem to be in accordance with literature data. Studies suggest that the TFF3 may play a role in different functions, such as proliferation, migration and angiogenesis, processes that when altered are crucial for tumorigenesis [37,39]. Indeed, TFF3 has been reported to be overexpressed at the gene and the protein level in human neoplasms and associated with poor prognosis.…”

<p>The Diagnosis, Treatment, Prognosis and Molecular Pathology of Borderline Ovarian Tumors: Current Status and Perspectives</p>

“…This result not only indicated that the development of SBOTs to invasive LGSOC involves a reduction in of p53 signal transduction but also suggested that p53 can inhibit the epithelial-mesenchymal transformation (EMT) process in SBOTs cells and thus the transformation to invasive ovarian cancer. El-Balat et al 66 further analyzed the expression of Trefoil factor-3 (TFF3) in 137 cases of BOT by immunohistochemistry and studied its relationship with histopathological characteristics. They found that the strong expression rate of TFF3 was 21.9% and there was no strong TFF3 expression in SBOTs and endometrial borderline tumors.…”

“…On the other hand, TFF3 was highly expressed in 61.4% of MBOT (P < 0.001), suggesting that TFF3 potentially plays a role in MBOTs. 66 In addition, insulin-like growth factor II mRNA binding protein 3 (IMP3) is considered a prognostic marker of ovarian clear cell carcinoma. 67 El-Balat et al 68 analyzed the expression of IMP3 in 140 cases of BOT in a cohort and found that the expression of IMP3 was not related to the age of patients, FIGO stage, microinvasion, or the presence of implants, but was related to the mucinous subtype of BOTs (mucinous vs other subtypes, 42.2% vs 9.5%, P < 0.001).…”