Prognostic Significance of Excision Repair Cross-Complementation Group 1 (ERCC1) Expression in Early Stage Resectable Non Small Cell Lung Cancer (NSCLC)
L Li, CE Sheehan, JS Ross. Albany Medical College, Albany, NY
Background: ERCC1 is an enzyme in the nucleotide excision repair pathway associated with the removal of damaged DNA after exposure to DNA damaging agents. Although the overexpression of ERCC1 mRNA and protein have been consistently associated with resistance to platinin-based chemotherapy and shortened survival in patients with recurrent or metastatic NSCLC, the significance or ERCC1 expression in early stage resectable NSCLC has not been widely studied.
Design: Formalin-fixed, paraffin embedded sections from 134 NSCLC, including 47 squamous cell carcinomas (SCC), 50 adenocarcinomas (AC), and 37 bronchioloalveolar carcinomas (BAC) were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) with mouse monoclonal ERCC1 (clone 8F1; Neomarkers). Nuclear immunoreactivity of each protein was semiquantitatively assessed in the tumor for all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive cells (focal <= 10%, regional 11-50%, diffuse >50%). Results were correlated with clinicopathologic variables.
Results: ERCC1 immunoreactivity was predominantly nuclear. ERCC1 overexpression was noted in 48/134 (35%) cases and correlated overall with tumor type [45% SCC vs 10% AC vs 50% BAC, p=0.013], small tumor size [43% <= 3.0cm vs 23% > 3.0cm, p=0.02], lengthened survival within the expired group [13% expired <12mos vs 33% expired 1 - 5 yrs vs 57% expired > 5yrs, p=0.001], and showed a trend toward lymph node negative status [42% LN negative versus 23% LN positive, p=0.062]. Within the SCC subgroup, ERCC1 overexpression correlated with small tumor size [75% <= 3.0cm versus 22% > 3.0cm, p=0.001] and lack of disease recurrence [50% non-recurrent vs 0% recurrent, p=0.05]. On multivariate analysis, only advanced tumor stage and positive lymph node status independently predicted patient survival.
Conclusions: In contrast with the adverse outcome for platinin-treated late stage, recurrent and metastatic ERCC1 positive NSCLC, in this study of early stage respectable NSCLC, overexpression of ERCC1 was a favorable prognostic factor for the disease. Further prospective validation of these findings in the prospective clinical trial setting including neo-adjuvant treatment selection appears warranted.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 232, Tuesday Afternoon