Evaluation of relationship of cancer stem cell markers and risk of recurrence in early stage non small cell lung cancer.

Background: Current cancer treatment failure is due to a small population of slow-growing and drug resistant cells known as cancer stem cells (CSCs). Unlimited self-renewal and exclusive tumerogenicity are hypothesized to be the properties of stem cells responsible for relapse. In Vitro studies have proved that NSCLC cells expressing certain markers (CD44, CD 133 and ALDH 1) have stem cell properties. We aimed to investigate the expression of three cancer stem cell markers (CD44, CD133, ALDH 1) in NSCLC and evaluated their prognostic values for postoperative relapse and correlation with histological subtypes. Method(s): Tumours were obtained from 102 patients with stage 1 NSCLC (both Adenocarcinoma and SCC) who underwent surgical resection (1999-2008). Sequentially sampled paraffin sections were immunoprobed with antibodies for CD44standard, CD133 and ALDH 1 followed by reaction with DAB-conjugated secondary antibodies. All slides were scored by an independent pathologist in a blinded manner. Statistical analysis was conducted where correlations between CSC biomarker expression, histological subtypes and cancer recurrence rates was performed. Cumulative risks for developing recurrence of lung cancer after curative treatment of primary tumours was calculated using the Kaplan-Meier method and was compared between the groups using the log-rank test. Result(s): 102 pts with age range of 42-84 (median 68) underwent radical surgery and were pathologically staged as WHO stage1A (64) or 1B (38). Median follow up was 60 months (10-108) where follow up data was unavailable for 2 patients. Within the patient population 39% had relapsed; 31% had distant and 8% locoregional relapses where within these relaspses, 17/63 (23%) were Stage 1A and 22/37(59%) stage 1B. Analysis demonstrated a higher expression of CD44 in Squamous Cell Carcinoma (SCC) than Adenocarcinoma (ACA). Within the 102 stained sections, 53% in SCC vs. 24% in ACA were positive for CD44 (p=0.005) with 61% of positi