The Ron proto-oncogene product is a phenotypic marker of renal oncocytoma

Am J Surg Pathol. 2003 Jun;27(6):779-85. doi: 10.1097/00000478-200306000-00008.

Abstract

The proto-oncogene product Ron is the receptor for macrophage stimulating protein, a scatter factor that stimulates cell proliferation, prevents apoptosis, and induces an invasive cell phenotype. We investigated the expression of Ron, Ki-67 (proliferation index), p53, and bcl-2 (proapoptotic and antiapoptotic proteins, respectively) in 50 renal tumors (19 clear cell carcinomas, 18 oncocytomas, 7 papillary cell carcinomas, 5 chromophobe cell carcinomas, and 1 carcinoma with sarcomatoid areas). In addition, we studied Ron in normal kidney and in the renal carcinoma cell line Caki-1. Immunostaining and Western blot showed Ron in normal kidney and in all oncocytomas but never in renal cell carcinomas or in Caki-1. In addition, Western blot showed that Ron was expressed in phosphorylated, i.e., active, form. Bcl-2 was strongly expressed in oncocytomas, whereas Ki-67 and p53 were much less expressed in oncocytomas than in carcinomas. These results indicate in Ron a marker that differentiates oncocytoma from the other renal epithelial tumors. We therefore think that Ron may prove to be a new tool for a sound and precise diagnosis of oncocytoma, a benign tumor that cannot always be distinguished from carcinomas at histologic examination. The overexpression of bcl-2, but not p53 in oncocytoma, suggests that the MSP/Ron system sustains the growth of oncocytoma by opposing apoptosis.

MeSH terms

  • Adenoma, Oxyphilic / genetics
  • Adenoma, Oxyphilic / metabolism*
  • Adenoma, Oxyphilic / pathology
  • Apoptosis
  • Biomarkers, Tumor*
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Phenotype
  • Protein Precursors / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • MAS1 protein, human
  • Protein Precursors
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • macrophage stimulating protein
  • Hepatocyte Growth Factor