Abstract

Abstract The aldehyde dehydrogenase (ALDH) enzymes are important for detoxification of endogenous and exogenous aldehydes. Expression of ALDH family members has recently been described as a potential marker for tumor-initiating cancer stem cells in a variety of human malignancies, including lung cancer. We were interested to determine whether expression of ALDH7A1, a member of the ALDH family, has prognostic significance in resected non-small cell lung carcinoma (NSCLC). Tumor specimens were obtained for 107 patients with completely resected stage I through stage III NSCLC from paraffin-embedded tissue microarrays and stained with an antibody specific for ALDH7A1. Staining patterns were graded by a pathologist based on the intensity of staining and the percentage of cells stained. A staining score index was calculated by multiplying intensity score by the percentage area with positive staining. An index of ≥100 was considered positive, while an index <100 was deemed negative, as determined by visually determining a clear positive stain supported by histograms of the range of scores. Staining index was subsequently correlated with clinical data. Positive ALDH7A1 staining was identified in 46 patients, and negative staining was noted in 48 patients, with 13 tumor sections missing. Multivariate analysis demonstrated that NSCLC patients with positive ALDH7A1 expression had decreased overall survival relative to ALDH7A1-negative tumors, although this did not reach significance (hazard ratio 1.42, 95% confidence interval 0.84 to 2.389; p=0.192). However, patients with ALDH7A1-expressing NSCLC tumors had a significantly higher incidence of lung cancer recurrence compared to patients with ALDH7A1-negative tumors (hazard ratio 6.24, 95% confidence interval 2.06 to 18.86; p=0.001). These data indicate that ALDH7A1 staining is present in a substantial number of NSCLC tumors and may be a biomarker predictive for increased incidence of cancer recurrence in patients with surgically resected NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2252. doi:10.1158/1538-7445.AM2011-2252

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