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

Authors

  • Yun Cao MD,

    1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangdong, China
    2. Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan
    3. National Cancer Center Singapore-Van Andel Research Institute Translational Research Laboratory, National Cancer Center Singapore, Singapore
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    • The first 2 authors contributed equally to this article.

  • Zhi-Ling Zhang MD, PhD,

    1. Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China
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    • The first 2 authors contributed equally to this article.

  • Ming Zhou MD, PhD,

    1. Pathology and Laboratory Medicine Institute, The Cleveland Clinic, Cleveland, Ohio
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  • Paul Elson ScD,

    1. Quantitative Health Science, The Cleveland Clinic, Cleveland, Ohio
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  • Brian Rini MD,

    1. Taussig Cancer Institute, The Cleveland Clinic, Cleveland, Ohio
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  • Hakan Aydin MD,

    1. Pathology and Laboratory Medicine Institute, The Cleveland Clinic, Cleveland, Ohio
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  • Kristin Feenstra PhD,

    1. Laboratory of Analytical, Cellular, and Molecular Microscopy, Program in Bio-Specimen Science, Van Andel Research Institute, Grand Rapids, Michigan
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  • Min-Han Tan MD,

    1. National Cancer Center Singapore-Van Andel Research Institute Translational Research Laboratory, National Cancer Center Singapore, Singapore
    2. Institute of Bioengineering and Nanotechnology, Singapore
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  • Bree Berghuis BS,

    1. Laboratory of Analytical, Cellular, and Molecular Microscopy, Program in Bio-Specimen Science, Van Andel Research Institute, Grand Rapids, Michigan
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  • Rebeka Tabbey MS,

    1. Department of Biostatistics, Indiana University, Indianapolis, Indiana
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  • James H. Resau PhD,

    1. Laboratory of Analytical, Cellular, and Molecular Microscopy, Program in Bio-Specimen Science, Van Andel Research Institute, Grand Rapids, Michigan
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  • Fang-Jian Zhou MD,

    1. Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Bin Tean Teh MD, PhD,

    1. Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan
    2. National Cancer Center Singapore-Van Andel Research Institute Translational Research Laboratory, National Cancer Center Singapore, Singapore
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  • Chao-Nan Qian MD, PhD

    Corresponding author
    1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangdong, China
    2. Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan
    • Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, 333 Bostwick Avenue N.E., Grand Rapids, MI 49503

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    • Fax: (011) 86-20-8734-3624;


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 [α-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. © 2012 American Cancer Society.

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