TETRAPLOID ARREST WITH OVEREXPRESSED NON-MUTATED P53 IN GERM-CELL CANCERS - RELEVANCE TO THEIR CHEMOSENSITIVITY AND POSSIBLE APPLICATION INNON-GERM CELL CANCERS

Immunocytochemical study of 40 germ cell cancers, 31 bladder cancers a nd 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 squa mous head and neck cancers were positive for p53 using Mab 240. In con trast 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. Th ere was a higher p53 positivity for the more chemoradiosensitive semin oma (82%, n=17) compared to non-seminoma (33%, n=6) and the inverse fo r Bcl-2 (53% vs. 83%). Taken together with emerging data that the puta tive stem cell for all germ cell cancers, the tetraploid pachytene pri mary spermatocyte normally expresses p53, these results support the vi ew that near tetraploid overexpression of functional p53 in germ cell cancer may be a factor in why germ cell cancers are more chemosensitiv e than the common adult cancers. They also highlight the need for bett er understanding of the cell cycle check points during meiosis as poss ible molecular targets that would increase the chemosensitivity of non -germ cell cancers.