Aldehyde Dehydrogenase 1 (ALDH1) Expression Is Associated with Clinical Outcome in Non Small Cell Lung Cancer (NSCLC)
L Li, CE Sheehan, JS Ross. Albany Medical College, Albany, NY
Background: ALDH1 is an enzyme involved in the regulation of intracellular retinoic acid metabolism. ALDH1 expression has been associated with solid tumor stem cells and progenitor cells and linked to resistance to chemotherapy. ALDH1 expression has not been widely studied in NSCLC.
Design: Formalin-fixed, paraffin embedded sections from 114 NSCLC, including 31 squamous cell carcinomas (SCC), 45 adenocarcinomas (AC), and 38 bronchioloalveolar carcinomas (BAC) were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) with mouse monoclonal ALDH1 (clone 44/ALDH; BD Biosciences). Cytoplasmic immunoreactivity was semiquantitatively assessed in the tumor for all cases. Scoring was based on staining intensity and percentage of tumor cells. Results were correlated with clinicopathologic variables.
Results: ALDH1 immunoreactivity was predominantly cytoplasmic. ALDH1 overexpression was noted in 54/114 (47%) tumors and correlated overall with tumor type [68% SCC vs 29% AC vs 45% BAC, p<0.0001], tumor grade [26% well differentiated vs 65% moderately differentiated vs 41% poorly differentiated, p=0.007], and gender [60% male vs 33% female, p=0.004]. Within the SCC subgroup, ALDH1 overexpression correlated with tumor grade [0% well differentiated vs 95% moderately differentiated vs 55% poorly differentiated, p=0.007], gender [88% male vs 43% female, p=0.013] and shortened overall survival [88% expired vs 43% expired, p=0.013]. On multivariate analysis, only advanced tumor stage and poor tumor differentiation independently predicted overall survival.
Conclusions: ALDH1 expression in NSCLC is associated with SCC tumor type, higher tumor grade and male patients. With in SCC subgroup, ALDH1 overexpression is positively correlated with higher tumor grade, male patients and poor survival. The potential role of ALDH1 in NSCLC as a prognostic factor and a predictor of chemoresistance warrants further study.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 237, Monday Morning