Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

Background: Expression levels of CD133, a cancer stem cell marker, and of the alpha-subunit of the dystroglycan (alpha-DG) complex, have been previously reported to be altered in colorectal cancers. Methods: Expression levels of CD133 and alpha-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. Results: Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0-80). A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002) and overall (p = 0.008) survival. Expression of alpha-DG was reduced in a significant fraction of tumors but low alpha-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in alpha-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but not loss of alpha-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002) and death (RR = 2.3; p = 0.003). Conclusions: Loss of alpha-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.