The purpose of this article is to review the recent advances in renal cell carcinoma (RCC) from a pathological point of view. Because the genetic features and morphological characteristics have become major criteria for the classification of RCC, special techniques, such as immunohistochemistry, are essential to the differential diagnosis of renal tumors. Metastasis is frequently observed among the RCC patients with curative nephrectomy, and extracellular matrix-degrading enzymes, such as matrix metalloproteinases (MMP) and heparanase, play a key role in invasion and metastasis of RCC. Snail and Slug, transcription factors of epithelial-mesenchymal transition (EMT), accelerate cancer cell invasion through downregulation of E-cadherin and up-regulation of MMP. Therapies targeted at the vascular endothelial growth factor pathway have become the standard treatment of metastatic RCC. Although they lead to tumor shrinkage mainly by inhibiting angiogenesis, they have typically been associated with drug resistance. The mechanism of the resistance remains largely unknown, but complex events including re-activation of angiogenesis, EMT and cancer stem cells, and immune escape are implicated in the refractory response to the therapy. Recent advances of the research on RCC have caused the changes of classification and therapy, and pathologists should take overall view of these as integrated pathology.
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