Combined Angiogenesis and Proliferation Markers' Expressions as Long-Term Prognostic Factors in Renal Cell Cancer

Clin Genitourin Cancer. 2016 Aug;14(4):e283-9. doi: 10.1016/j.clgc.2015.12.014. Epub 2015 Dec 22.

Abstract

Objectives: The aim of this study was to evaluate the expression of MIB-1, BCL-2, VEGFR3, and CD31 and their associations with long-term survival in patients with renal cell cancer (RCC).

Patients and methods: This study consisted of 224 RCC patients who underwent radical nephrectomy from 1985 to 1995. Follow-up continued for up to over 20 years. MIB-1 and BCL-2 expression were analyzed alone, and additionally, the expression of MIB-1, BCL-2, VEGFR3, and CD31 were combined in pairs using the following groups: low/low, low/high, high/low, and high/high.

Results: Low BCL-2 expression (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.42-3.31; P < .001 compared with high BCL-2 in univariate analysis) and high MIB-1 expression (HR, 2.05; 95% CI, 1.32-3.19; P = .001 in multivariate analysis) were found to associate for poorer survival in RCC. In multivariate analysis, the combination of high MIB-1/low BCL-2 was associated with poor survival compared with low MIB-1/high BCL-2 (HR, 3.20; 95% CI, 1.66-6.17; P = .001), and the combination of low VEGFR3/high CD31 was associated with poor survival (HR, 2.48; 95% CI, 1.29-4.78; P = .007) compared with high VEGFR3/high CD31.

Conclusions: Compared with high BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression, low BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression has poorer survival in the long-term follow-up of patients with RCC. Analysis of MIB-1, BCL-2, VEGFR3, and CD31 expression might be a useful additional marker to tailor the follow-up of RCC patients.

Keywords: BCL-2; CD31; MIB-1; RCC; VEGFR3.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality*
  • Carcinoma, Renal Cell / surgery
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ki-67 Antigen / metabolism
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality*
  • Kidney Neoplasms / surgery
  • Male
  • Middle Aged
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Survival Analysis
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism

Substances

  • BCL2 protein, human
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proto-Oncogene Proteins c-bcl-2
  • FLT4 protein, human
  • Vascular Endothelial Growth Factor Receptor-3