Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival.
BACKGROUND
The relationship between excision repair cross-complementation group 1 (ERCC1) expression and outcome, in patients with malignant pleural mesothelioma (MPM), treated with cisplatin/vinorelbine combination-therapy, was retrospectively evaluated in a patient population from a previously published phase II clinical trial.


METHODS
The study population consisted of 54 inoperable patients with MPM enrolled between 2003 and 2006. ERCC1 expression was evaluated by immunohistochemistry (IHC) on the formalin-fixed paraffin-embedded diagnostic biopsies. The immunoreaction was quantified using an H-score (staining intensity multiplied by a proportion score based on the percentage of stained tumor cells). The cutoff point was chosen as the median H-score in a cohort of non-neoplastic pleural samples from patients with benign thoracic diseases. The tumor samples were separated according to this cutoff point into ERCC1-negative (H-score ≤ median) and ERCC1-positive (H-score > median) cases.


RESULTS
Fifty patients had tumor tissue available for IHC. There were 20 ERCC1-positive and 30 ERCC1-negative tumors. There was a significant correlation between negative ERCC1 status and long progression-free survival (PFS). Median PFS was 10.9 months in the ERCC1-negative group, opposed to 6.7 months in the ERCC1-positive group (p = 0.053). Multivariate Cox regression showed ERCC1 to be the only variable significantly associated with PFS, and ERCC1-positive patients had a significantly shorter time to progression compared with ERCC1-negative patients (hazard ratios, 2.24; 95% confidence interval, 1.16-4.34; p = 0.0163). We found no association between ERCC1 status and overall survival.


CONCLUSIONS
Our retrospective study in MPM patients treated with cisplatin/vinorelbine suggests that low ERCC1 expression, evaluated by IHC, may predict longer PFS, a result that warrants further validation.
Department of Pathology, National University Hospital of Copenhagen, Rigshospitalet, Denmark. zarah.zimling@rh.regionh.dk
Zarah Glad
ZG
Zimling
Jens Benn
JB
Sørensen
Thomas Alexander
TA
Gerds
Cecilia
C
Bech
Claus Bøgelund
CB
Andersen
Eric
E
Santoni-Rugiu
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage; D016001:Confidence Intervals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D014747:Vinblastine; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D000077235:Vinorelbine