Defect of tropomyosin-related kinase B isotype expression in ovarian clear cell adenocarcinoma

Abstract

Tropomyosin-related kinase B (TrkB) is a functional signal molecule that correlates with cell survival and epithelial-mesenchymal transition (EMT), which is essential for the invasiveness of malignant cancer cells. While a truncated isoform of TrkB has a dominant negative effect, full-length TrkB with its tyrosine kinase domain is predicted to play a role in cancer progression. Because ovarian clear cell adenocarcinoma (CCA) shows worse prognosis compared to other cancer types, we investigated the correlation between TrkB isoforms and the progression of CCA. Ovarian adenocarcinoma and benign tumor samples were obtained from Tokai University Hospital and Juntendo University Hospital. These samples were examined for the TrkB expression of isotype-specific proteins and mRNAs by immunohistochemistry and domain-specific semi-quantitative reverse transcription polymerase chain reaction. While TrkB mRNA expression was detected in all of the ovarian tissues and TrkB protein expression was predominant in ovarian cancer tissues, the number of tissues expressing the tyrosine kinase-truncated isoforms (T-Shc or T1) decreased according to the clinical stage of CCA. Irregular isoforms were also observed in some CCA samples. The decrease in T-Shc and T1 were less obvious in mucinous adenocarcinoma and not observed in serous or endometrioid adenocarcinoma. Decreased expression of the truncated isoforms (T-Shc and T1) was associated with CCA progression. These results demonstrate that irregular expression of TrkB isoforms is a characteristic of CCA tissues. The unique TrkB expression profile may be useful for the diagnosis of CCA subtypes.