IDENTIFICATION OF TP53 GENE-MUTATIONS IN UTERINE CORPUS CANCER WITH SHORT FOLLOW-UP

The involvement of the TP53 tumor suppressor gene in uterine corpus ca ncer was investigated by single-stranded conformation polymorphism and sequence analysis of its exons 4 to 10. Mutations were found in 12 (1 8.5%) of 65 cases. Ten of these 12 were single-base substitutions (8 m issense and 2 nonsense mutations), whereas 2 were frame-shifting mutat ions. TP53 gene mutations correlated significantly with advanced surgi cal stage of disease (P = 0.006) and unfavorable tumor histology types (P = 0.003), whereas the association to myometrial wall invasion did not reach statistical significance (P = 0.054). TP53 gene mutations al so correlated significantly with allelic loss at TP53 locus (P = 0.024 ), absence of estrogen (P = 0.045) and progesterone receptors (P = 0.0 01), DNA nondiploidy (P = 0.002), and high S-phase fraction values (P = 0.002). Our results suggest that inactivation of the TP53 checkpoint function is associated with disease transition into a stage of rapid progression and spread. (C) 1997 Academic Press.