PLATINUM-SENSITIVE AND PLATINUM-RESISTANT OVARIAN-CANCER TISSUES SHOWDIFFERENCES IN THE RELATIONSHIPS BETWEEN MESSENGER-RNA LEVELS OF P53,ERCC1 AND XPA

We investigated the association between p53 mRNA expression and clinic ally relevant surrogates of nucleotide excision repair (ERCC1 and XPA) in 28 ovarian cancer specimens. We observed that platinum-resistant t umors showed higher mRNA levels of p53, ERCC1, and XPA than platinum-s ensitive tumors; mRNA expression patterns in responders differed subst antially from nonresponders; and p53 expression showed a strong correl ation with the expression of ERCC1, and of XPA in platinum-sensitive t umor tissues, but not with platinum-resistant tumors. 47% of the mutat ions from p53 sequence analysis were not related to clinical response to chemotherapy. We conclude that the p53 influence on DNA repair in h uman malignancy may vary substantially from tumor to tumor, and that s uch differences are not necessarily related to the mutational status o f p53.