UROLOGY – ORIGINAL PAPER Angiogenesis in renal cell carcinoma: correlation of microvessel density and microvessel area with other prognostic factors Shree Gopal Sharma • Nidhi Aggarwal • Siddhartha Datta Gupta • Manoj Kumar Singh • Ruchika Gupta • Amit Kumar Dinda Received: 16 August 2006 / Accepted: 20 May 2010 / Published online: 10 June 2010 Ó Springer Science+Business Media, B.V. 2010 Abstract This study was aimed at evaluating the association between tumor vascularity and other known prognostic factors in different histopatholo- gical subtypes of renal cell carcinoma (RCC). In 41 cases of RCC, immunohistochemistry was performed using anti-CD34 antibody and Ki-67 (MIB-1). Micro- vessel density was estimated in an area of 0.23 mm 2 representative of the highest microvessel density (‘‘hot spot’’). The microvessel area (MVA) was expressed as percentage of total tumor area occupied by vessels. Endothelial proliferation index (EPI) was determined from sections stained by Ki-67. The relationship between MVD, MVA, EPI and prognostic parameters of RCC like stage, grade and tumor cells proliferation index (TPI) was evaluated. The tumor MVA increased significantly with the higher stage of the tumor (P \ 0.001) and increase in TPI (P \ 0.05). The MVD, however, did not show significant correlation with grade and stage of the tumor. Microvessel area appears to be a better prognostic marker for RCC when compared to microvessel density. The increase in MVA, without increase in MVD, with increasing stage may be due to the development of larger diameter vascular channels in higher-stage tumors, and this is thought to facilitate metastasis. Keywords Microvessel area Á Microvessel density Á Renal cell carcinoma Á Stage Á Tumor grade Introduction Angiogenesis is the formation of new capillaries from the existing vascular network and is essential to tumor growth and metastases [1]. Folkman [1] described the role of angiogenesis in tumor growth and metastasis. He demonstrated that a tumor could grow up to 1.75 mm without neo-angiogenesis when it obtained nutrients only by diffusion. Assessment of angiogenesis has been shown to be an important prognostic predictor of breast carci- noma, prostatic adenocarcinoma and squamous cell carcinoma of head and neck. However, its role in renal cell carcinoma is controversial with conflicting reports in literature [2–4]. The angiogenesis may be assessed in several ways such as microvessel density (MVD), microvessel area (MVA), quantifying angio- genic molecules within the tumor, assessing the presence of angiogenic receptors within the tumor tissue, measuring angiogenic factors within the serum and urine of patients with cancer [2–6]. Of all these methods, MVD is the most extensively studied parameter and has been applied for a wide variety of tumors besides RCC [2, 3]. The measurement of intratumoral MVD is accepted as an important prognostic indicator in several malignant neoplasms, S. G. Sharma Á N. Aggarwal Á S. D. Gupta Á M. K. Singh Á R. Gupta Á A. K. Dinda (&) Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India e-mail: amit_dinda@yahoo.com 123 Int Urol Nephrol (2011) 43:125–129 DOI 10.1007/s11255-010-9779-7