Biologic Behavior of and p53 Overexpression in Multifocal Renal Cell Carcinoma of Clear Cell Type: An Immunohistochemical Study Correlating Grading, Staging, and Proliferation Markers

Cancer. 1999 Apr 1;85(7):1593-8. doi: 10.1002/(sici)1097-0142(19990401)85:7<1593::aid-cncr22>;2-k.


Background: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established.

Methods: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage.

Results: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival.

Conclusions: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell / pathology*
  • Cell Division
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Proliferating Cell Nuclear Antigen / analysis
  • Tumor Suppressor Protein p53 / analysis*


  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • Tumor Suppressor Protein p53