Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis

Abstract

Microvessel density (MVD), an indicator of angiogenesis, has been proposed to predict prognosis of patients with renal cell carcinoma (RCC), but its ability to predict survival of patients with RCC remains controversial. The present study sought to address this question rigorously by systematically reviewing the literature on MVD and RCC prognosis. We identified relevant studies in PubMed, EMBASE and the Cochrane Library, and two reviewers independently assessed study quality and extracted relevant data to compare survival based on MVD stratification in patients with RCC. We identified 15 studies that satisfied the inclusion criteria; eight studies assessed MVD in surgical samples by immunohistochemistry to label factor VIII; four studies, by immunohistochemistry to label CD34; two studies, CD31; and one study, CD105. Survival meta-analysis was performed using data pooled from 10 studies: five based on factor VIII, two based on CD34, two based on CD31 and one based on CD105. The overall survival hazard ratio describing the relationship between MVD and survival in all 10 pooled studies was 0.964 (95% CI: 0.873-1.065), while the individual hazard ratios for pooled studies based on factor VIII were 1.673 (95% CI: 0.860-3.252); CD34, 0.903 (95% CI: 0.853-0.956); and CD31, 0.926 (95% CI: 0.868-0.989). The corresponding result for the sole trial based on CD105 was 0.1759 (95% CI: 0.036-0.856). These findings suggest that MVD is not reliably associated with survival time of patients with RCC, which may reflect the need to take into account whether the microvasculature is differentiated or not. MVD as currently calculated may not be an ideal prognostic factor for patients with RCC.

Keywords: Microvessel density; meta-analysis; prognosis; renal cell carcinoma.

Figure 1

Flow chart of study selection and meta-analysis.

Figure 2

Meta-analysis of studies assessing the relationship of overall survival of RCC patients with MVD measured based on labelling of CD34, CD31, FVIII, or CD105. HR > 1 indicates an association between higher MVD and poor overall survival. HRs were estimated using a DerSimonian and Laird random-effects model.

Figure 3

Begg’s funnel plot to assess bias among the 10 studies in the meta-analysis.

Figure 4

Egger’s funnel plot to assess publication bias among the 10 studies in the meta-analysis.