Expressió de KIT i PDGFR en tumors de cèllules renals. Discussió del seu paper com a possibles dianes terapèutiques
ENGLISH SUMMARY: Renal Cell Neoplasms (RCN) represent 3% of cancer incidence and comprise different clinicopathologic entities. Malignant subtypes, specially the most frequent one Clear Cell Renal Cell Carcinoma (CRCC), remain the most lethal of urologic cancers due to the high rate of patients (30-50%) developing metastatic disease for whom new therapies are needed. Great advances in molecular biology have led to the identification of tyrosine-kinase receptors (TKR) as relevant proteins in tumorigenesis. Moreover the advent of selective inhibitors against them has raised interest on its expression in different tumors. PDGFR and KIT are two examples of TKR that have an oncogenic role in numerous neoplasms and can be inhibited pharmacologically. Because of its potential role as proto-oncogens and therapeutic targets; We aimed to study its immunohistochemical expression in RCN and to discuss its possible role as molecular targets. Our results highlight specific expression of KIT in Chromophobe renal cell carcinoma (ChRCC) and Renal Oncocytoma (RO). Overexpression of KIT and PDGFR? was found in sarcomatoid differentiation of renal tumours (SRCC) without mutations in KIT exons 9,11,13,17 nor PDGFR exons 11,12,17,18 which are the most commonly mutated in GIST. Moreover inespecific and low expression of PDGFR? and PDGFR? was evidenced in tumoral cells in different RCN. In contrast, vascular expression of PDGFR? was seen caracteristically in half of CRCC cases. According to our results, we propose KIT as a useful marker for differential diagnosis among RCN. Moreover we demonstrate that expression of KIT and PDGFR in SRCC doesn´t follow the same pathogenetic mecanism as GIST. Scientific community claims that immunohistochemical expression of a protein in a tumor is not enough to propose it as a therapeutic target and that demonstation of its pathogenetic role is needed. So as, there is still no evidence of participation of KIT-PDGFR in ChRCC, OR nor SRCC oncogenesis, there is not enough data to propose them as therapeutic targets. Conversely, in different studies PDGFR? has been involved in CRCC pathogenesis and has been related to tumor angiogenesis by perycite recruitment. So that, vascular expression of PDGFR? in CRCC favours its consideration as a therapeutic target in this tumor subtype.
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Advisor:Mallofré Gómez, Carme
School:Universitat de Barcelona
Source Type:Master's Thesis
Keywords:anatomia patològica farmacologia i microbiologia
Date of Publication:11/14/2008