Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival

TY - JOUR

T1 - Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival

AU - Zimling, Zarah Glad

AU - Sørensen, Jens Benn

AU - Gerds, Thomas Alexander

AU - Bech, Cecilia

AU - Andersen, Claus Bøgelund

AU - Santoni-Rugiu, Eric

PY - 2012/1

Y1 - 2012/1

N2 - Introduction: 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. Conclusion: 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.

AB - Introduction: 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. Conclusion: 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.

U2 - 10.1097/jto.0b013e318233d6a9

DO - 10.1097/jto.0b013e318233d6a9

M3 - Journal article

C2 - 22031231

SN - 1556-0864

VL - 7

SP - 249

EP - 256

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

IS - 1

ER -