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* From the Thoracic Oncology Program (Drs. Simon, Smith, and Bepler, and Mr. Sharma) and Biostatistics Core (Dr. Cantor), Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
Correspondence to: George R. Simon, MD, FCCP, Assistant Professor of Medicine, Thoracic Oncology Program & Experimental Therapeutics Program, H Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Dr, Ste# 3170, Tampa FL 33612; e-mail: simongr{at}moffitt.usf.edu
Study objectives: Proteins of the nucleotide excision repair pathway repair DNA damage. The excision repair cross-complementing (ERCC) gene family reduces damage to DNA by nucleotide excision and repair. Impaired nuclear excision repair could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. We therefore evaluated the effect of intratumoral ERCC1 expression on survival in non-small cell lung cancer (NSCLC) patients who underwent surgical resection for cure.
Design: Resected tumor and the corresponding normal lung specimens from 51 patients with NSCLC who underwent surgical resection were immediately frozen in liquid nitrogen. Total RNA was extracted, reverse transcribed, and amplified with intron-spanning primers. Quantitation for ERCC1 was done using the Taqman procedure, and gene expression was normalized using 18SrRNA expression as internal reference with ERCC1 levels expressed a unit-less ratio.
Results: Tumoral ERCC1 expression ranged from 4.96 to 2,008, with a median value of 54.76. Using an ERCC1 value of 50 to dichotomize the cohort, there was a statistically significant difference in median survival for patients with ERCC1 expression > 50 (94.6 months) compared to < 50 (35.5 months) [p = 0.01]. Multivariate analysis revealed that high ERCC1 expression independently predicted for longer survival. There were no significant correlations between ERCC1 expression in tumor tissue and normal lung.
Conclusions: We conclude that resected NSCLC patients with high ERCC1 expression (> 50) have a better survival when compared to patients with low ERCC1 expression (< 50). We postulate that an intact DNA repair mechanism may reduce the accumulation of genetic aberrations that are thought to contribute to a tumors malignant potential and therefore the risk of relapse after definitive treatment. Future adjuvant and neoadjuvant chemotherapy trials in NSCLC could stratify patients according to their ERCC1 expression levels.
Key Words: adenocarcinoma • non-small cell lung cancer and prognosis • nuclear excision repair genes • squamous cell carcinoma
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