The relationship of platinum resistance and ERCC1 protein expression in epithelial ovarian cancer.
OBJECTIVE
Although platinum-based chemotherapy remains the cornerstone for treatment of ovarian cancer, some patients are resistant to the treatment and will therefore not benefit from the standard platinum-based chemotherapy. Preclinical and clinical data have suggested a potential use of excision repair cross-complementation group 1 enzyme (ERCC1) as a molecular predictor of clinical resistance to platinum-based chemotherapy. Excision repair cross-complementation group 1 enzyme is a key enzyme in the nucleotide excision repair pathway which is involved in the DNA repair mechanisms in tumor cells damaged by treatment with platinum agents. The primary aim of the present study was to investigate if immunohistochemical expression of ERCC1 protein was associated with resistance to standard combination carboplatin and paclitaxel chemotherapy in newly diagnosed ovarian cancer patients.


METHODS
Formalin-fixed, paraffin-embedded tissue sections from 101 patients with newly diagnosed ovarian cancer were used for immunohistochemical staining for the ERCC1 protein. All patients received carboplatin-paclitaxel combination chemotherapy.


RESULTS
Excision repair cross-complementation group 1 enzyme protein overexpression was found in 13.9% of the tumors. Platinum resistance was found in 75% of the tumors with positive ERCC1 protein expression compared with 27% among the patients with negative tumor staining for ERCC1 (P = 0.0013). These findings translated into a significant difference in progression-free survival in both univariate (P = 0.0012) and in multivariate analysis (P = 0.006).


CONCLUSIONS
The data presented suggest a positive association between positive ERCC1 protein expression and clinical resistance to platinum-based chemotherapy.
Steffensen
Karina Dahl
KD
Department of Oncology, Vejle Hospital, Vejle, Denmark. Karina.Dahl.Steffensen@slb.regionsyddanmark.dk
Waldstrøm
Marianne
M
Jakobsen
Anders
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel