期刊
HUMAN PATHOLOGY
卷 40, 期 4, 页码 496-504出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2008.09.011
关键词
Hepatocyte growth factor receptor; Matrix metalloproteinases; E-cadherin; Prognosis; Bladder cancer
类别
资金
- Japan Society for the Promotion of Science (Tokyo, Japan) [17791080]
- Grants-in-Aid for Scientific Research [17791080] Funding Source: KAKEN
Hepatocyte growth factor receptor/c-Met is associated with malignant aggressiveness and survival in various cancers including bladder cancer. Although phosphorylation of hepatocyte growth factor receptor/c-Met is essential for its function, the pathologic significance of phosphorylated hepatocyte growth factor receptor/c-Met in bladder cancer remains elusive. We investigated the clinical significance of its expression, and its correlation with cancer cell progression-related molecules. The expression levels of 2 tyrosine residues of hepatocyte growth factor receptor/c-Met (pY1234/1235 and pY 1349) were examined immunohistochemically in 133 specimens with non-metastatic bladder cancer. We also investigated their correlation with matrix metalloproteinase-1, -2, -7, and -14; urokinase-type plasminogen activator; E-cadherin; CD44 standard, variant 3, and variant 6; and vascular endothelial growth factor. Expression of phosphorylated hepatocyte growth factor receptor/c-Met was detected in cancer cells, but was rare in normal urothelial cells. Although hepatocyte growth factor receptor/c-Met, pY 1234/1235 hepatocyte growth factor receptor/c-Met, and pY 1349 hepatocyte growth factor receptor/c-Met were associated with pT stage, multivariate analysis identified pY 1349 hepatocyte growth factor receptor/c-met expression only as a significant factor for high pT stage. Expression of pY1349 hepatocyte growth factor receptor/c-Met was a marker of metastasis and (P = .001) and cause-specific survival (P = .003). Expressions of matrix metalloproteinase-2, matrix metalloproteinase-7, and E-cadherin correlated with pY1349 hepatocyte growth factor receptor/c-Met expression. Our results demonstrated that pY1349 hepatocyte growth factor receptor/c-Met plays an important role in tumor development, and its expression is a significant predictor of metastasis and survival of patients with bladder cancer. The results suggest that these activities are mediated, at least in part, by matrix metalloproteinase-2, matrix metalloproteinase-7, and E-cadherin. (C) 2009 Elsevier Inc. All rights reserved.
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