ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients.
BACKGROUND
ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents.


OBJECTIVE
Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance.


METHODS
Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene.


RESULTS
Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders.


CONCLUSIONS
We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.
Dabholkar
M
M
Medicine Branch, National Cancer Institute, Bethesda, Md. 20892.
Bostick-Bruton
F
F
Weber
C
C
Bohr
V A
VA
Egwuagu
C
C
Reed
E
E
D015139:Blotting, Southern; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D015331:Cohort Studies; D004265:DNA Helicases; D015342:DNA Probes; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005260:Female; D015870:Gene Expression; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis; D012074:Remission Induction; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein
D015342:DNA Probes; D004268:DNA-Binding Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D014157:Transcription Factors; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin