Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis

p19(INK4d) a member of the INK4 family of cyclin-dependent kinase inhibitors, negatively regulates the proto-oncogenic cyclin D/CDK4(6) complexes whose ability to phosphorylate the retinoblastoma tumour suppressor (RB) promotes G1/S transition. In contrast to the related p16(INK4a) tumour suppressor, expression patterns of 19(INK4d) in human tissues and tumours remain unknown. As the RE pathway is commonly targeted in cancer, and mouse models suggest a role for p19(INK4d) in spermatogenesis, ne examined the abundance and localization of p19(INK4d) in the human testis, both during normal development and at various stages of germ-cell tumour pathogenesis. Our data show that the p19(INK4d) protein is abundant in spermatocytes of normal human adult testes, whereas virtually no p19(INK4d) is detectable in testicular cancer, including the preinvasive carcinoma ill situ stage. Together with the lack of p19(INK4d) in human foetal germ cells, these results support the concept of foetal origin of the testicular germ-cell tumours, and help better understand the emerging role of the RE pathway in spermatogenesis and tumorigenesis in the human testis.