Measurement of aldehyde dehydrogenase 1 expression defines a group with better prognosis in patients with non-small cell lung cancer.

Aldehyde dehydrogenase 1 (ALDH1) has been suggested as a surrogate biomarker for cancer stem cells in breast cancer and other tumors. We quantitatively measured ALDH1 in two large cohorts of patients with non-small cell lung cancer (NSCLC) and investigated its prognostic value. The AQUA method of quantitative immunofluorescence was used to measure ALDH1 in 134 patients with NSCLC from Yale University and 296 patients with NSCLC from Sotiria and Patras University hospitals in Greece, using tissue microarrays. Patients were classified as positive or negative for ALDH1 based on the detection threshold for quantitative immunofluorescence. Patients with squamous cell carcinoma had higher scores than patients with adenocarcinoma. Detectable ALDH1 predicted better prognosis in both cohorts (P = 0.0035 for the Yale cohort; P = 0.0238 for the Sotiria/Patras cohorts). The effect of ALDH1 expression was independent of clinicopathologic factors in the Yale cohort (risk ratio = 3.2, P = 0.0008), but did not reach significance in the Sotiria/Patras cohort (hazard ratio = 1.51, P = 0.08). Among patients with adenocarcinoma, the ALDH1-negative group had shorter survival compared with the ALDH1-positive group in the Yale cohort (P = 0.00001), but not in the Sotiria/Patras cohort (P = 0.45). Unlike breast cancer, in which ALDH1 expression predicts poor outcome, in NSCLC our exploratory and retrospective study indicates that ALDH1 expression is associated with favorable outcome.