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


CONCLUSIONS
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.
Togo
Nozomi
N
Department of Surgery, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma, Japan.
Ohwada
Susumu
S
Sakurai
Shinji
S
Toya
Hiroyuki
H
Sakamoto
Ichiro
I
Yamada
Tatsuya
T
Nakano
Tetsuhiro
T
Muroya
Ken
K
Takeyoshi
Izumi
I
Nakajima
Takashi
T
Sekiya
Takashi
T
Yamazumi
Yusuke
Y
Nakamura
Tsutomu
T
Akiyama
Tetsu
T