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Int. J. Mol. Sci. 2014, 15(7), 13060-13076; doi:10.3390/ijms150713060

Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Via Orazio Flacco n° 65, 70100 Bari, Italy
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Received: 28 May 2014 / Revised: 17 July 2014 / Accepted: 17 July 2014 / Published: 23 July 2014
(This article belongs to the Special Issue Molecular Research in Urology 2014)
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Abstract

Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC. View Full-Text
Keywords: renal cell carcinoma; c-Kit receptor; stem cell factor; mast cells; microvessel density; molecular targeting agents renal cell carcinoma; c-Kit receptor; stem cell factor; mast cells; microvessel density; molecular targeting agents
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Marech, I.; Gadaleta, C.D.; Ranieri, G. Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma. Int. J. Mol. Sci. 2014, 15, 13060-13076.

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