Nozomi Togo, Susumu Ohwada, Hiroyuki Toya, Ichiro Sakamoto, Tatsuya Yamada, Tetsuhiro Nakano, Ken Muroya, Izumi Takeyoshi, Departments of Surgery, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
Shinji Sakurai, Takashi Nakajima, Departments of Tumor Pathology, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
Takashi Sekiya, Yusuke Yamazumi, Tsutomu Nakamura, Tetsu Akiyama, Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan
Author contributions: Togo N and Ohwada S contributed equally to this work; Togo N, Ohwada S, Sakurai S, Toya H, Nakajima T and Akiyama T designed research; Togo N, Toya H, Muroya K performed research; Akiyama T contributed new reagents; Togo N, Ohwada S, Nakajima T and Akiyama T analyzed data and wrote the paper.
Supported by Grants from the Japan Science and Technology Agency, No. 17014011; The Harunasou Foundation Cancer Research Subsidizing Fund; The Kanetsu Chuo Hospital Research Fund; And research funds from the Uchida Clinic in Inamachi, Saitama; The Katoh Clinic, Maebashi Norte Hospital in Maebashi, Gunma; And Keiaido Hospital in Midori, Gunma
Correspondence to: Susumu Ohwada, Department of Surgery, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan. go.go.ohwada@gmail.com
Telephone: +81-279-233030 Fax: +81-279-232740
Received: May 23, 2008 Revised: August 12, 2008 Accepted: August 17, 2008 Published online: August 21, 2008
Abstract
AIM: To investigate the clinical significance of BMP and activin membrane-bound inhibitor (BAMBI) which is a pseudoreceptor of transforming growth factor-beta (TGF-β) type I receptors and acts as a negative regulator of TGF-β 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-β-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 β-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 (RR 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.
