title: Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study.
abstract: Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti-angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results. Previous studies were limited by manual quantification of MVD within a small area of tumor. Since then, the validity of this method has been questioned. To avoid the inaccuracies of manual quantification, we employed a computerized image analysis, which allowed assessment of large areas of tumor and adjacent normal tissue. The latter was used as an internal reference for normalization. MVD and vascular endothelial growth factor (VEGF) were assessed in 57 cases of ccRCC. Sections were immunostained for CD34 and VEGF. Areas of ccRCC and normal kidney medulla were analyzed within scanned images using software that counted CD34-positive vessels and measured the intensity of VEGF staining. We obtained unadjusted values from tumoral areas and calculated adjusted values as tumor/normal ratios. Unadjusted MVD had no association with clinical outcome. However, similarly to tumor stage, higher adjusted MVD was associated with shorter disease-free survival (log-rank P=0.037, Cox P=0.02). This was significant in univariate and multivariate analyses. MVD did not correlate with tumor stage, pointing to its independent prognostic value. As expected due to the known molecular abnormalities in ccRCC, most tumors showed higher VEGF expression than normal tissue. Higher adjusted VEGF was associated with high tumor grade (P=0.049). The finding of increased MVD as an independent marker of tumor aggressiveness may prove useful in the development of new tests for prognostic and therapeutic guidance. Digital techniques can provide more accurate assessment of immunomarkers and may reveal less obvious associations.
authors: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors: Vladimir V
authors: VV
authors: Iakovlev
authors: Manal
authors: M
authors: Gabril
authors: William
authors: W
authors: Dubinski
authors: Andreas
authors: A
authors: Scorilas
authors: Youssef M
authors: YM
authors: Youssef
authors: Hala
authors: H
authors: Faragalla
authors: Kalman
authors: K
authors: Kovacs
authors: Fabio
authors: F
authors: Rotondo
authors: Shereen
authors: S
authors: Metias
authors: Androu
authors: A
authors: Arsanious
authors: Anna
authors: A
authors: Plotkin
authors: Andrew H F
authors: AH
authors: Girgis
authors: Catherine J
authors: CJ
authors: Streutker
authors: George M
authors: GM
authors: Yousef
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D042461:Vascular Endothelial Growth Factor A