Prognostic Value of MET, RON and Histoprognostic Factors for Urothelial Carcinoma in the Upper Urinary Tract

PurposeRON (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.Materials and MethodsWe 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.ResultsPatient 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).ConclusionsIndependent 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.