Expression of RON Proto-oncogene in Renal Oncocytoma and Chromophobe Renal Cell Carcinoma

Am J Surg Pathol. 2004 Aug;28(8):1045-50. doi: 10.1097/01.pas.0000128661.58697.7d.


Recently, it was reported that RON proto-oncogene, encoding a receptor tyrosine kinase, was strongly expressed in renal oncocytomas but not in any renal cell carcinomas, including 5 chromophobe renal cell carcinomas, which morphologically resemble oncocytomas. To determine its diagnostic value, we studied Ron protein expression by immunohistochemistry in a larger number of renal cell neoplasms with emphasis on chromophobe renal cell carcinomas. Tissue microarrays containing 141 renal cell neoplasms, including 55 oncocytomas and 52 chromophobe renal cell carcinomas, were constructed. In addition, conventional sections from 15 cases of oncocytoma and 5 cases of chromophobe renal cell carcinoma were analyzed. Immunohistochemistry was carried out with a monoclonal mouse anti-human Ron-alpha antibody. Staining intensity was scored on a 0 to 3 scale. Ninety-nine percent of oncocytomas (69 of 70) and 96% of chromophobe renal cell carcinomas (55 of 57) showed moderate to strong, diffuse cytoplasmic Ron immunoreactivity with intensities > or =2, while only 17% of other renal cell carcinoma subtypes stained with intensities > or =2. Our study indicates that Ron immunostaining cannot be used to distinguish oncocytoma from chromophobe renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Oxyphilic / genetics*
  • Adenoma, Oxyphilic / metabolism
  • Adenoma, Oxyphilic / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Female
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Oxyphil Cells* / metabolism
  • Oxyphil Cells* / pathology
  • Protein Array Analysis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Staining and Labeling


  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • macrophage stimulating protein
  • Hepatocyte Growth Factor