Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma

Abstract

BACKGROUND. The objective of this study was to evaluate the effect of pericyte coverage (PC) of differentiated tumor microvessels on the prognosis of patients with clear cell renal cell carcinoma (CCRCC). METHODS. Samples from 2 cohorts of patients with CCRCC (101 Asian patients and 524 US patients) were prepared using 2 different histologic approaches: routine sectioning versus tissue microarray. Then, the samples were immunohistochemically doubled-stained for a pericyte marker (alpha smooth muscle actin [a-SMA]) and a differentiated vessel marker (cluster of differentiation 34 [CD34]), followed by multispectral image capturing and computerized image analyses to quantify the microvessel density (MVD) and the PC of differentiated vessels. The correlations of PC and the MVD:PC ratio with clinicopathologic characteristics were analyzed. RESULTS. There was an inverse correlation between differentiated MVD and PC. Higher PC correlated with more aggressive clinicopathologic characteristics of CCRCC in both cohorts, including more advanced T-classification, higher pathologic grades, and the occurrence of tumor necrosis. The MVD:PC ratio was an independent favorable prognostic factor for overall and recurrence-free survival in the Asian cohort and for recurrence-free survival in the US cohort. PC also was an independent prognostic factor, with higher PC predicting a poorer outcome. The combination of PC and MVD was better at distinguishing the outcome of patients with CCRCC. PC combined with differentiated MVD or with the MVD:PC ratio provided additional, independent prognostic information to the Leibovich risk model, and that information was used to generate improved risk models. CONCLUSIONS. The authors consistently observed that higher PC was correlated with more aggressive clinicopathologic characteristics. PC was an independent unfavorable prognostic factor. The authors concluded that pericytes should be considered for therapeutic targeting. Cancer 2013;119:313-34.

The Effect of VEGF-Targeted Therapy on Biomarker Expression in Sequential Tissue from Patients with Metastatic Clear Cell Renal Cancer

“…Conceivably, upregulated expression of MET in the vascular compartment could help facilitate this mechanism of acquired resistance. Pericyte coverage of vessels in human tumors is variable, with conflicting reports about the prognostic significance (32,33). Our results show that high baseline levels of pericyte coverage correlate with a poor outcome, supporting previous work in RCC (33).…”

“…Pericyte coverage of vessels in human tumors is variable, with conflicting reports about the prognostic significance (32,33). Our results show that high baseline levels of pericyte coverage correlate with a poor outcome, supporting previous work in RCC (33). Conflicting data also exist about the effects of antiangiogenic therapy on pericyte coverage (32,34,35).…”

Expression of cluster of differentiation 34 and vascular endothelial growth factor in breast cancer, and their prognostic significance

“…In particular, CD34 is particularly sensitive to tumor angiogenesis, as it can clearly represent the state of neovascularization during the growth of a tumor (3). Vascular endothelial growth factor (VEGF), a factor involved in vascular endothelial proliferation, can specifically promote cell proliferation and angiogenesis, and is closely associated with the growth, invasion and metastasis of tumors.…”

Relationships between the Effect of Sunitinib and Immature Blood Vessels in Metastatic Renal Cell Cancer

“…However, the functional role of pericytes in cancer progression remains unknown. A higher pericyte coverage has been correlated with more aggressive clinicopathological characteristics, and pericyte coverage has been noted as an independent unfavorable prognostic factor [29]. However, in colorectal cancer, pericyte coverage has been shown to have a significant negative correlation with hematogenous metastasis, and patients with a low pericyte coverage have been reported to have a significantly poorer survival than patients with a high pericyte coverage [30].…”