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Abstract
BackgroundExpression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers.MethodsExpression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated.ResultsScattered 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 α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-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 α-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).ConclusionsLoss of α-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.
Highlights
Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers
Loss of α-DG expression is a frequent event in colon cancers and correlates with the clinical outcome of patients We previously reported that α-DG expression, as assessed by western blot analysis, is frequently lost in human colon cancer cell lines and primary tumours and correlates with tumour grade and stage
Further studies will be required to fully understand the biological significance of the observed relationship between the two molecules. To our knowledge, this is the first study analyzing the immunohistochemical expression of both CD133 and αDG, two surface molecules previously reported to be altered in human colorectal cancers, in a large series of colon cancer patients
Summary
Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers. Dystroglycan (DG) is a non-integrin adhesion molecule expressed in a wide variety of tissues at the interface between the basement membrane and the cell membrane [4]. It is formed by two subunits, the α (extracellular) and β (transmembrane) subunits which bind to the major ECM components and proteins involved in signal transduction and cytoskeleton organization, respectively. We and others demonstrated that DG expression, and mainly α-DG, is reduced or lost in a variety of human cancer cell lines and primary tumours and overall, the available findings indicate that loss of DG expression is a frequent event in human malignancies and might play an important role in human tumour development and progression [4,5,6,8,9,10]
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