title: Nuclear EGFR characterize still controlled proliferation retained in better differentiated clear cell RCC.
abstract: Renal cell carcinoma (RCC) is the most common solid kidney tumor representing 2-3% of all cancers, with the highest frequency occurring in Western countries. There was a worldwide and European annual increase in incidence of approximately 2% although incidence has been stabilized in last few years. One third of the patients already have metastases in the time of the diagnosis with poor prognosis because RCC are radio and chemoresistant. The prognostic value of EGFR over-expression in RCC is a controversial issue that could be explained by different histological types of study tumors and non-standardized criteria for evaluation of expression. Recent evidences points to a new mode of EGFR signaling pathway in which activated EGFR undergoes nuclear translocalization and then, as transcription factor, mediates gene expression and other cellular events required for highly proliferating activities. According to our observations, the membranous expression of EGFR associates with high nuclear grade and poor differentiated tumors. On the other hand, nuclear EGFR expression was high in low nuclear graded and well differentiated tumors with good prognosis. We hypothesize that this mode of EGFR signaling characterizes still controlled proliferation retained in well differentiated RCC with Furhman nuclear grade I or II.
authors.affiliation: Department of Urology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia.
authors.forename: J
authors.initials: J
authors.lastname: Ahel
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia. Electronic address: gordana.dordevic@medri.uniri.hr.
authors.forename: G
authors.initials: G
authors.lastname: Dordevic
authors.affiliation: Department of Urology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia.
authors.forename: D
authors.initials: D
authors.lastname: Markic
authors.affiliation: Medico Polyclinic, Agatićeva 8, 51000 Rijeka, Croatia.
authors.forename: V
authors.initials: V
authors.lastname: Mozetic
authors.affiliation: Department of Urology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia.
authors.forename: J
authors.initials: J
authors.lastname: Spanjol
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: B
authors.initials: B
authors.lastname: Grahovac
authors.affiliation: Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Stifter
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003198:Computer Simulation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors