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Two Distinct Types of Blood Vessels in Clear Cell Renal Cell Carcinoma Have Contrasting Prognostic Implications

Authors' Affiliations: ¹ Laboratory of Cancer Genetics, ² Laboratory of Molecular Epidemiology, and ³ Laboratory of Analytical, Cellular and Molecular Microscopy, Laboratory of Microarray Technology, Van Andel Research Institute, Grand Rapids, Michigan; ⁴ Department of Urological Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; ⁵ Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China; ⁶ Department of Medical Oncology, National Cancer Centre, Singapore; ⁷ Department of Molecular Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; and ⁸ Surgical Pathology, Northwestern University Feinberg School of Medicine, Feinberg, Chicago, Illinois

Requests for reprints: Bin Tean Teh, Laboratory of Cancer Genetics, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503. Phone: 616-234-5296; Fax: 616-234-5297; E-mail: Bin.Teh{at}vai.org.

Purpose: Intratumoral microvascular density (MVD) has been controversial as an indicator of prognosis in clear cell renal cell carcinoma (CCRCC). Classification of the intratumoral blood vessels based on differential expressions of blood vessel markers has not been correlated with patient prognosis in CCRCC. In this study, we aimed to evaluate the association of different categories of blood vessels with the patients' outcomes.

Experimental Design: Seventy-eight CCRCC patients who underwent nephrectomy alone were enrolled. Paraffin-embedded CCRCC tissues, together with 16 nonmalignant kidney cortex tissues, were used in tissue microarray analyses and conventional section analyses. The characteristics of intratumoral blood vessels were identified by multiple blood vessel markers and pericyte markers. A computerized image analysis program was used to quantitatively calculate the vascular density.

Results: Two distinct types of microvessels were identified in CCRCC: undifferentiated (CD31⁺/CD34^–) and differentiated (CD34⁺) vessels. A higher undifferentiated MVD significantly correlated with higher tumor grades and shorter patient survival. In contrast, a higher differentiated MVD significantly correlated with lower tumor grade and longer survival. Multivariate analyses showed that undifferentiated MVD was an independent prognostic factor for patient survival. An inverse correlation between undifferentiated MVD and differentiated MVD was also identified in CCRCC.

Conclusions: This is the first report showing distinct types of vasculature in CCRCC correlated with contrasting prognoses. A refined classification of CCRCC based on vasculature is therefore important for evaluating prognosis, and it may also have therapeutic implications.

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