Tetraploid arrest with overexpressed non-mutated p53 in germ cell cancers

Immunocytochemical study of 40 germ cell cancers, 31 bladder cancers and 27 squamous head and neck cancers using monoclonal antibodies (Mab) specific for p53, Bcl-2 and HSP70 was carried out. The results showed that 89% of germ cell cancer compared to 7% of bladder and 2% of squamous head and neck cancers were positive for p53 using Mab 240. In contrast only 60% of germ cell cancers (20% strong) but 100% of bladder (80% strong) and head and neck (75% strong) were positive for Bcl-2. There was a higher p53 positivity for the more chemoradiosensitive seminoma (82%, n=17) compared to non-seminoma (33%, n=6) and the inverse for Bcl-2 (53% vs. 83%). Taken together with emerging data that the putative stem cell for all germ cell cancers, the tetraploid pachytene primary spermatocyte normally expresses p53, these results support the view that near tetraploid overexpression of functional p53 in germ cell cancer may be a factor in why germ cell cancers are more chemosensitive than the common adult cancers. They also highlight the need for better understanding of the cell cycle check points during meiosis as possible molecular targets that would increase the chemosensitivity of non-germ cell cancers.