The purpose of this study was to investigate retrospectively the
mRNA expression of genes involved in different DNA repair pathways implicated in processing
platinum-induced damage in 171
chemotherapy-naïve ovarian tumours and correlate the expression of the different genes with clinical parameters. The expression of genes involved in DNA repair pathways (PARP1, ERCC1, XPA, XPF, XPG, BRCA1, FANCA, FANCC, FANCD2, FANCF and
PolEta), and in DNA damage transduction (Chk1 and Claspin) was measured by RT-PCR in 13 stage I borderline and 77 stage I and 88 III ovarian
carcinomas. ERCC1, XPA, XPF and XPG genes were significantly less expressed in stage III than in stage I
carcinoma; BRCA1, FANCA, FANCC, FANCD2 gene expressions were low in borderline tumours, higher in stage I
carcinomas and lower in stage III samples. High levels of ERCC1, XPA, FANCC, XPG and
PolEta correlated with an increase in Overall Survival (OS) and Progression Free Survival (PFS), whilst high BRCA1 levels were associated with PFS on univariate analysis. With multivariate analyses no genes retained an association when adjusted by stage, grade and
residual tumour. A tendency towards a better PFS was observed in patients with the highest level of ERCC1 and BRCA1 after
platinum-based
therapy than those given both
platinum and
taxol. The expression of DNA repair genes differed in borderline stage I, stage I and stage III ovarian
carcinomas. The role of DNA repair genes in predicting the response in
ovarian cancer patients seems far from being established.