Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels

Abstract

To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.

Vascular architectural patterns in clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma

“…In contrast to the metastatic potential of CCRCC, ccpRCC shows an indolent behavior; therefore, accurate tumor classification is very important for patients' management and prognosis. Different studies have evaluated the prognostic significance of tumor vascularity in renal cell tumors with two different approaches, either quantification of microvessels by histomorphometry (MVD) [20][21][22][31][32][33][34], or vascular architectural patterns [33,35]. Although Weidner et al [24] have reported that von Willebrand and factor VIII are the most specific vascular markers for measuring intratumoral MVD in solid tumors, they acknowledged that CD31 and CD34 are more sensitive.…”

“…The microscopic assessment of vascular architectural patterns was based on four patterns, highlighted by CD34, derived from Ruiz-Saurí et al [33] model, based on the shape of vessels, presence of lumen, and interconnection, and modified as follows:…”

“…Many studies have evaluated the microvessel density in tumors from different anatomical sites using immunostains for CD31, CD34, factor VIII, VEGF, D2-40, and von Willebrand factor [26][27][28][29][30]. MVD in CCRCC has been addressed in previous studies [20][21][22][31][32][33][34]. Vascular architectural patterns have also been previously studied in CCRCC, chromophobe, papillary, and unclassified RCC using CD31, CD34, and SMA [33,35]; however, neither MVD nor vascular architectural patterns have been studied in ccpRCC.…”

“…MVD in CCRCC has been addressed in previous studies [20][21][22][31][32][33][34]. Vascular architectural patterns have also been previously studied in CCRCC, chromophobe, papillary, and unclassified RCC using CD31, CD34, and SMA [33,35]; however, neither MVD nor vascular architectural patterns have been studied in ccpRCC. ERG, a reliable endothelial cell marker [36], has recently been reported as novel prognostic marker in CCRCC [37], although, at the best of our knowledge, endothelial cell density (ECD) has not been analyzed in renal cell tumors.…”

The Fractal Dimension-Based Descriptor of the Microvascular Pattern on the Histological Section

“…The microvascular density, i.e., the surface density of capillaries on the two-dimensional histological section, is commonly used to description of the microvascular network. Changes of the microvascular network are associated with several pathologies including cardiovascular diseases [3], metabolic syndrome [4], and tumors [5].…”