Prognostic value of MET, RON and histoprognostic factors for urothelial carcinoma in the upper urinary tract

• Published in: The Journal of urology Vol. 179; no. 3; p. 868
• Main Authors: Compérat, E, Roupret, M, Chartier-Kastler, E, Bitker, M O, Richard, F, Camparo, P, Capron, F, Cussenot, O
• Format: Journal Article
• Language: English
• Published: United States 01.03.2008
• Subjects: Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Male; Middle Aged; Prognosis; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Urologic Neoplasms - genetics; Urologic Neoplasms - metabolism; Urologic Neoplasms - pathology; Urologic Neoplasms - surgery
• ISSN: 1527-3792
• DOI: 10.1016/j.juro.2007.10.079

RON (recepteur d'origine Nantais) (Santa Cruz Technology, Santa Cruz, California) and c-met (Dako, Glostrup, Denmark) are members of the c-met proto-oncogene family. c-met encodes a receptor tyrosine kinase and has a role in oncogenesis. RON has a role in cell transformation and epithelial tumorigenesis. Over expression of the 2 genes has been demonstrated in human bladder cancer. We explored whether over expression of the 2 proteins has a role in the tumorigenesis and defined histoprognostic factors of poor clinical outcomes in patients with these tumors. We reviewed the records of 42 patients with upper urinary tract urothelial carcinoma. A total of 24 tumors were localized in the renal pelvis and 18 were in the ureter. Immunohistochemical staining for RON and c-met was performed using tissue microarrays. Patient age was 46 to 100 years (mean 70.6). Of the patients 23 (54%) died of disease. Over expression of c-met was associated with a higher risk of embolism (p = 0.0002), while over expression of RON was not significantly associated with emboli (p = 0.5). Univariate analysis showed that relapse was significantly associated with ureteral localization (p = 0.02), vascular invasion (p = 0.003), and high grade (p = 0.04) and high stage (0.02) urothelial carcinoma. The association with vascular invasion, and high grade and high stage urothelial carcinoma was also statistically significant (p <0.0001). Notably superficial tumors showed an important relapse rate (p = 0.003). Independent prognostic factors of relapse in upper urinary tract urothelial carcinoma are ureteral localization, vascular invasion, high grade and high stage. c-met seems to influence the development of vascular invasion via an unknown mechanism. Nevertheless, to our knowledge an association between c-met over expression and aggressive clinical behavior in upper urinary tract carcinomas has not been previously reported.