Molecular Diagnostics

British Journal of Cancer (2005) 92, 1906–1914. doi:10.1038/sj.bjc.6602593 www.bjcancer.com
Published online 3 May 2005

Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder

H-L Cheng1,7, H-S Liu2,7, Y-J Lin2, H H-W Chen3, P-Y Hsu4, T-Y Chang5, C-L Ho4,6, T-S Tzai1 and N-H Chow4,6

  1. 1Department of Urology, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan
  2. 2Departments of Microbiology and Immunology, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan
  3. 3Department of Radiation Oncology, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan
  4. 4Institute of Basic Medical Sciences, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan
  5. 5Department of Parasitology, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan
  6. 6Department of Pathology, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan

Correspondence: Dr N-H Chow, Department of Pathology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 70428, Taiwan. E-mail: chownh@mail.ncku.edu.tw

7These two authors contributed equally to this study

Received 27 October 2004; Revised 7 March 2005; Accepted 24 March 2005; Published online 3 May 2005.

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Abstract

Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment.

Keywords:

bladder cancer, protein tyrosine kinases, RON, MET, co-expression, prognosis