Expression of the homologous gene pair TSPY and TSPX in patients with testicular tumours

The TSPY is the evolutionary conserved multi-copy gene family linked to Y chromosome with function in early spermatogenesis, immediately prior to the spermatogonia-tospermatocyte transition, and in early testicular tumorigenesis. Expression of TSPY has been reported in various solid tumours, including germ cell tumours (gonadoblastoma, seminoma, carcinoma in situ, etc.) and somatic tomours (melanoma, hepatocellular carcinoma, epithelial prostate cancer, etc.). TSPY protein is known to positively regulate cell cycle progression, in particular accelerates G2/M transition, by interaction with cyclin B. Within this interaction TSPY competes with its X chromosome homologue – TSPX. On the contrary, the TSPX exerts the function of cell cycle inhibitor by transcriptional up-regulation of p21 associated with ERK1/2 kinase. Furthermore, TSPY is a transcriptional repressor of androgen receptor activity, indicative of its putative function in hormone-dependent cancer.

We studied the TSPY/TSPX expression on formalin fixed paraffin embedded testicular tumour samples (92) by indirect immunohistichemistry staining method. Patient samples were staged and divided based on the diagnosis into: i) 50 seminoma samples; ii) 22 embryonal carcinoma samples and iii) 20 mixed germ cell tumour samples.

Our data show enhanced nuclear positivity for TSPY and TSPX in basal parts of normal seminiferous ducts, as well as in intratubular germ cell neoplasia (IGCNU). We found statistically significant difference in both nuclear and cytosolic positivity of TSPY in seminoma (high TSPY) and embryonal carcinoma (low TSPY). Loss of nuclear TSPY expression correlated positively with angioinvasion and higher stage of malignancy. Moreover, lowered TSPY positivity in embryonal carcinoma was found to be associated with increased nuclear TSPX expression. Interestingly, increased nuclear TSPY expression was in correlation with decreased TSPX nuclear expression in seminoma.

Our study supports the role of the nuclear TSPY and TSPX expression as a diagnostic markers for differential diagnostic of seminoma and embryonal carcinoma samples.

Acknowledgement: This work was supported by grant GAČR 303/09/H048, Operational Programme Research and Development for Innovations (project CZ.1.05/2.1.00/01.0030) and by the Ministry of Education of the Czech Republic - grant MSM 6198959216.