title: Recent advances in renal cell carcinoma from a pathological point of view.
abstract: 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.
authors.affiliation: Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mizuno
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo, Japan.|Department of Urology, Saiseikai Tobu Hospital, Yokohama, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.affiliation: Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Tohto College of Health Science, Saitama, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Katsube
authors.affiliation: Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D002292:Carcinoma, Renal Cell / Q000473:pathology*; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*
keywords: cancer stem cell; epithelial and mesenchymal transition; molecular-targeted therapy; renal cell carcinoma; resistance