Poster Presentation 25th Lorne Cancer Conference 2013

The prognostic significance of ALDEHYDE DEHYDROGENASE 1 (ALDH1) and CD133 expression in early-stage non-small cell lung cancer. (#417)

Alamgeer Muhammad 1 , Anette Szczepny 1 , Beena Kumar 2 , David Neil Watkins 1 , Wright Gavin 3 , Zdenka Prodanovic 4 , Vinod Ganju 5
  1. Monash Institute of Medical Research, Clayton, Vic, Australia
  2. Anatomical pathology, Monash Medical Centre, Clayton, Vic, Australia
  3. Cardiothoracic surgery, St Vincent Hospital, Fitzroy, Vic, Australia
  4. Pathology, Monash Medical Centre, Clayton, Vic, Australai
  5. Medical Oncology, Monash Medical Centre, East Bentleigh, Vic, Australia

Background: Expression of ALDH1 and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with enhanced stem-like properties that manifest as recurrence and/or metastasis following definitive surgical resection of early stage disease. The aim of this study was to evaluate the prognostic significance of ALDH1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC).

Methods: A retrospective analysis of ALDH1 and CD133 expression in 205 patients with pathologic Stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers, overall survival and recurrence-free survival was determined.

Results:  We identified 61 relapses and 58 cancer-related deaths in 144 Stage1A and 61 Stage 1B patients, analyzed at a median of 5 years follow-up. Overexpression of ALDH1 and CD133 was detected in 68.7% and 50.7% of primary tumours, respectively. Overexpression of ALDH1 or CD133 was independent prognostic indicator for overall survival by multivariate Cox proportional hazard model (p = 0.01 and 0.03 respectively). Overexpression of ALDH1 but not CD133 predicated poor recurrence free survival (p = 0.02). When categorized into three groups according to expression of ALDH1/CD133, patients with overexpression of both ALDH1 and CD133 belonged to group with shortest recurrence free and overall survival (p = 0.01 and 0.01, respectively). Further analysis according to hsitological subtypes showed that ALDH1 was strongly expressed in SCC (p = 0.002) while CD133 was strongly expressed in ADC (p = 0.001). Prognostic value of these markers was also different in two histological subtypes.

Conclusions: Expression of ALDH1 and CD133, and co-expression of ALDH1 and CD133, is strongly associated with poor survival in early stage NSCLC following surgical resection. These data are consistent with hypothesis that expression of stem cell markers correlates with recurrence as in an indirect measure of self-renewal capacity.