The expression of the high-mobility group A2 protein in colorectal cancer and surrounding fibroblasts is linked to tumor invasiveness.

Tumor staging of colorectal cancer is typically based on conventional TNM and Dukes classifications. However, additional information could be useful, and there is a significant interest in identifying molecular markers that are related to genetic or epigenetic processes. Using immunohistochemistry, we analyzed the expression of the high-mobility group A2 (previously high-mobility group 1-C [HMGI-C]) protein in 103 colorectal cancer cases to determine its use as a biomarker in colorectal cancer to integrate morphological staging. We found a progressive increase of the high-mobility group A2 protein expression in colorectal cancer tumor samples from cases in which all of the tumor cells were negative up to cases in which all of the tumor cells stained positive. Increased high-mobility group A2 expression is strongly associated with an increase in tumor invasiveness, which was measured through both budding and vascular invasion (P < .0001). Kaplan-Meier estimates showed a decrease in overall survival when vascular invasion is present (P = .023). Moreover, a fraction of the analyzed samples showed high-mobility group A2-positive stromal fibroblasts. Although high-mobility group A2-positive tumors were associated with cell invasiveness, high-mobility group A2-positive stromal fibroblasts were correlated with less invasive tumors. High-mobility group A2 protein expression could be used as a prognostic marker to provide prospective information on patient outcome, complementing the data obtained using conventional pathologic staging systems.