title: Expression of DNA repair genes in ovarian cancer samples: biological and clinical considerations.
abstract: 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.
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy. monica.ganzinelli@marionegri.it
authors.forename: M
authors.initials: M
authors.lastname: Ganzinelli
authors.forename: P
authors.initials: P
authors.lastname: Mariani
authors.forename: D
authors.initials: D
authors.lastname: Cattaneo
authors.forename: R
authors.initials: R
authors.lastname: Fossati
authors.forename: R
authors.initials: R
authors.lastname: Fruscio
authors.forename: S
authors.initials: S
authors.lastname: Corso
authors.forename: F
authors.initials: F
authors.lastname: Ricci
authors.forename: M
authors.initials: M
authors.lastname: Broggini
authors.forename: G
authors.initials: G
authors.lastname: Damia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel