Abstract
Background: Recent studies suggested a possible existence of cancer stem cells in non-small cell lung cancer (NSCLC). We evaluated the expression of proteins involved in Sonic-hedgehog (Shh) pathway and their prognostic significance in curatively resected NSCLC. In addition, we compared the expression of these proteins with the other stem cell (SC) related molecules including BMI-1, beta-catenin and ALDH-1. Methods: One hundred and thirty-seven patients with resected NSCLC were included in this retrospective study. We used immunohistochemistry to evaluate the expression of Shh, Smoothened (Smo), Patched (Ptc), Gli-1, BMI-1, beta-catenin and ALDH1 on tissue microarray in duplicate. We assessed disease free survival (DFS) and overall survival (OS). Results: 60% of patients had stage I disease, 17% stage II, 18% stage IIIA, and 5% stage IIIB. All patients received complete resection. Among the molecules involved in Shh pathway, Smo was positive in 106 (77%) patients. Patients with a positive Smo expression survived longer than did the patients with a negative expression (5-year overall survival rate was 57% vs. 32%; P<0.001 / 5-year disease free survival rate was 50% vs. 28%; P=0.011). Shh, Ptc and Gli-1 expression did not affect OS and DFS significantly. A multivariate Cox proportional hazard analysis that incorporated covariates including Smo expression, stage, histology, and age showed that Smo expression was an independent favorable prognostic factor for overall survival (hazard ratio 0.376; P<0.001). A comparison with other SC related molecules showed that Smo was co-expressed with BMI-1 (p=0.026). BMI-1 was positive in 96 (70%) patients. Patients with a positive BMI-1 expression had a tendency for longer OS and DFS (p=0.263 and p=0.193, respectively). When BMI-1 and Smo are considered together, double positivity for BMI-1 and Smo was strongly related to longer OS and DFS (p<0.001 and p=0.002, respectively). Beta-catenin and ALDH-1 expression were associated with neither SMO expression nor prognosis. Conclusions: Smo and BMI-1 are the SC related molecules that have a prognostic impact in NSCLC. To the contrary to conventional conjectures, Smo and BMI-1 expression was related to good prognosis in patients with resected NSCLC.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2564.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO