Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer

AIM: To investigate the clinical significance of BMP and activin membrane-bound inhibitor (BAMBI) which is a pseudoreceptor of transforming growth factor-beta (TGF-beta) type I receptors and acts as a negative regulator of TGF-beta signaling and expression aberrantly elevated in colorectal cancers (CRCs). We studied BAMBI expression in CRCs. METHODS: We studied BAMBI expression in 183 surgically resected CRCs by immunochemical and immunoblotting analyses using a generated monoclonal anti-BAMBI antibody. Commercially available anti-beta-catenin and anti-p53 antibodies were also applied for immunochemical analyses as a comparison control. RESULTS: Immunohistochemical analysis revealed that BAMBI expression was observed in 148 (80.8%), and strong BAMBI expression was observed in 46% of the CRCs. Strong BAMBI expression was positively correlated with histological type, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (P < 0.05). Clear associations were found between BAMBI and beta-catenin (P = 0.035) and p53 (P =0.049) expression. In curatively resected CRC, 5-year recurrence-free survival was 51.9% (P = 0.037) for strong BAMBI expression compared to 79.8% for weak BAMBI expression. In the Cox's multivariate analysis, lymph node metastases (relative risk 6.685; P < 0.001) and depth of invasion (RR 14.0; P = 0.013) were significant indicators for recurrence, and strong BAMBI expression (RR 2.26; P = 0.057) tended to be significant. CONCLUSION: BAMBI was linked to a potentially aggressive tumor phenotype and predicted tumor recurrence and cancer-related death in CRC. BAMBI expression might be applicable in the routine clinical setting of CRC. (c) 2008 The WJG Press. All rights reserved.