Matriptase and MET are prominently expressed at the site of bone metastasis in renal cell carcinoma: immunohistochemical analysis

Abstract

High MET expression in renal cell carcinoma (RCC) and MET activation in bone metastases are reportedly important in progression of several cancers. To find new treatment targets in bone metastasis, we immunohistochemically analyzed expression levels of MET and matriptase (specific cellular activator of hepatocyte growth factor). We obtained nephrectomy specimens from 17 RCC patients with metastasis, and bone metastases specimens from 7 RCC patients who underwent metastasectomies, and who were treated at our hospital between 2008 and 2012. We tested the samples with anti-human MET polyclonal antibody and anti-human matriptase polyclonal antibody, and compared postoperative overall survival (OS) rates between positive and negative groups. High MET expression was seen at primary sites in 8/17 (47 %) nephrectomy specimens, and 6/7 (86 %) bone specimens. Matriptase was expressed in 6/17 (35 %) nephrectomy specimens, and all 7 (100 %) bone specimens. Interestingly, matriptase was strongly expressed in osteoclasts of 5/7 bone specimens. Postoperative OS rate was significantly higher in the MET− group than the MET+ group. The high MET and matriptase expression seen in RCC cells in bone metastasis accompanied by matriptase expression in osteoclasts indicates their importance in bone metastasis.