The Transmembrane Protease Serine (TMPRSS3/TADG-12) D Variant: A Potential Candidate for Diagnosis and Therapeutic Intervention in Ovarian Cancer

Abstract

The purpose of this study was to examine the expression of splice variants of the TADG-12 (TMPRSS3) gene in normal ovarian epithelial tissue and ovarian carcinoma and further to associate the expression of TADG-12 variant with clinicopathologic characteristics if such an association exists. TADG-12D variant expression was examined by semiquantitative PCR in 50 ovarian tumors [41 adenocarcinomas, 3 low malignant potential (LMP) tumors, and 6 adenomas] and 7 normal ovaries. In carcinomas as well as LMP tumors and adenomas, TADG-12D variant mRNA expression was significantly elevated compared to that in normal ovary samples. TADG-12 has several splice variants, one of which we originally identified and 3 others identified by Scott et al. [Nat Genet 2001;27:59–63]. We previously examined the expression of TADG-12V variant and here we confirm the overexpression of TADG-12D variant in ovarian carcinomas. Moreover, TADG-12D variant mRNA expression level in carcinomas was significantly elevated compared to that in adenomas and TADG-12D variant mRNA expression level in advanced clinical stage diseases was significantly higher than that in early stage diseases in ovarian carcinomas. With regard to histological type, TADG-12D variant mRNA expression level in mucinous adenocarcinomas was significantly higher than those in the other tissue subtypes. These features imply that TADG-12D variant expression may play an important role in ovarian cancer development and progression, and this variant may be useful both as a molecular target for therapy and/or a diagnostic marker.