Association of increased levels of stem cell marker ALDH1 with overall survival in metastatic colon cancer.

Abstract

e14635 Background: The clinical relevance of cancer stem cells (CSC’s) in solid organ malignancies is unclear. ALDH1 is thought to be a universal marker of stemness and is expressed in normal and neoplastic stem cells. We sought to determine the effects of stemness, expressed as levels of ALDH1, on survival for similarly staged metastatic colon cancer patients. Methods: Patients with lymph node positive colon cancer and unresectable liver metastasis diagnosed from 2004-2009 were identified. Sections were prepared from paraffin blocks and stained with an ALDH1 antibody. To determine quantitative expression of ALDH1, morphometric analysis with a Nikon microscope, SPOT video camera, and ImagePro software was performed with expression defined as stained area/total area. Ten to twenty randomly selected fields from were assessed. Patients were determined to have high expression of ALDH1 if respective levels were above the mean. Data analysis was performed with JMP. Results: A total of 16 patients were identified, with a median age of 64 years. The majority of patients were female (63%) and black (69%). Few primary tumors were poorly differentiated (25%). Median survival was 21.5 months (range: 1-47). Mean expression of ALDH1 was 0.041+0.01 for normal crypts, 0.031+0.01 for lymph node metastases, and 0.062+0.02 for primary tumors. ALDH1 expression was high in 31.3%, 20%, and 31.3% of patients for normal colon crypts, lymph node metastases, and primary cancers, respectively. Increased expression ALDH1 in tumors was strongly correlated with mortality (p=0.0013) and male sex (p=0.0166), but not with age (p=0.71) or race (p=0.50). Increased expression of ALDH1 in primary tumors was associated with a decreased overall survival, 27 vs. 6 months (p=0.0015). Increased expression of ALDH1 in normal colon crypts and lymph node metastases was not associated with survival, 27 vs. 19 (p=0.18) and 21 vs. 22 months (p=0.35), respectively. Conclusions: Increased stemness in primary colon cancers, expressed as ALDH1 levels, is associated with poor survival for similarly staged metastatic patients. These data suggest that an increase in stem cell fraction predicts a more aggressive clinical course.