Testis-specific protein Y-encoded (TSPY) is overexpressed in hepatocellular carcinoma and may play a role in male predominance

Abstract

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer worldwide and shows a male predominance of 3–4:1. Testis-specific protein Y-encoded (TSPY) is a Y-encoded gene that is mapped within the critical region of gonadoblastoma locus on Y-chromosome (GBY). TSPY is expressed in normal testicular germ cells and was found to be expressed in cancers such as germ cell tumors. While TSPY is considered a proto-oncogene according to its biological functions, the correlation between TSPY expression and HCC development has not been fully characterized. METHODS AND RESULTS: We analyzed the expression of TSPY in 40 pairs of human HCC samples (33 male and 7 female patients) surgically resected at Queen Mary Hospital, Hong Kong. Total RNA was isolated from each of the pairs of HCC and their corresponding nontumorous liver tissues and analyzed with RT-PCR using specific primers for TSPY mRNA (1–229 nt of the coding region). TSPY was detected in 9 (27%) of the 33 HCC cases from male patients. TSPY expression was detectable only in the tumorous tissues and not in the corresponding non-tumorous liver tissues. No TSPY expression was detected in any cases from female patients. Immunohistochemical analysis with TSPY antibody showed expression results corresponding to those of RT-PCR. TSPY immunoexpression was correlated with that of glypican-3 (GPC3) and proliferation marker Ki67. HBV expression (HBV[219-683 nt] region) was detected in 25 (76%) of the 33 male cases and 4 (57%) of the 7 female cases. No significant association between HBV expression and TSPY mRNA expression levels was observed. CONCLUSIONS: TSPY was overexpressed in 27% of the HCCs from male patients. TSPY overexpression in male HCC patients may be implicated in HCC tumorigenesis and may potentially play a role in male predominance of HCC. Further investigation of the functions and role of TSPY in HCC is awaited.