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Rho GTPases are overexpressed in human tumors. bPIX is a specific guanine nucleotide exchange factor for Rhoproteins Rac1 and Cdc42. This study was aimed to evaluate whether bPIX is overexpressed, and it affects the clinical behavior of colon cancer.Immunohistochemistry and Western blot were performed in the tissues from normal human colons, hyperplastic polyps, adenomas and adenocarcinomas. Nuclear and cytoplasmic immunostaining was evaluated by a combined histoscore (staining intensity x percentage of stained area). Correlation of bPIX expression with clinicopathology was then assessed.βPIX expression was upregulated with increasing order of hyperplastic polyp < adenoma < adenocarcinoma. Interestingly, nuclear staining of bPIX wasprominent in hyperplastic polyp and adenoma, while bPIX stained mainly in the cytoplasm of adenocarcinoma. Expression of bPIX was greater in adenocarcinomas than in their paired normal tissues. Nuclear expression of bPIX was rarely observed in the advanced stages of cancer, (III and IV). bPIX expression levels either in the cytoplasm or in the nucleus correlated well with cellular differentiation. However, tumor invasion showed an inverse correlation with the expression levels of cytosolic or nuclear bPIX.Overexpression of bPIX may be involved in colon carcinogenesis, and related with betterprognosis.