Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas

Receptor for advanced glycation end products (RAGE) is associated with invasion, metastasis, and poor prognosis in colorectal cancer. We studied the expression of RAGE in colorectal adenomas to elucidate the role of RAGE in cancer development. Expressions of RAGE and high-mobility group box-1 (HMGB1)/amphoterin RAGE ligand were examined in 96 colorectal adenomas using immunohistochemistry and in situ hybridization, respectively. Positivity and expression pattern of RAGE were compared with atypia, histological types, size, and HMGB1/amphoterin expression. Of 96 adenomas, 34 (35%) showed RAGE expression. RAGE positivity was significantly higher in adenomas with severe atypia (18/20, P<0.0001) and large-sized adenomas (−15 mm) (18/22, P<0.0001). RAGE expression showed three patterns: cytosolic (n=10), luminal (n=14), and membranous (n=10). Cytosolic pattern was associated with mild atypia and small size (−5 mm). Membranous pattern was associated with severe atypia, villous histological type, and co-expression with overexpressed HMGB1/amphoterin. These results suggest that RAGE expression, especially with membranous pattern, is associated with malignant potential of colorectal adenomas.