title: Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups.
  
  
  METHODS
  We retrospectively collected clinical data of 137 patients treated with partial or radical nephrectomy at our institutions for organ-confined, locally advanced, and metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical expression was compared with pathological and clinical features including age, sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between tumor stages was performed via Kruskal-Wallis nonparametric test. Survival analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel log-rank test was employed to compare survival among groups.
  
  
  RESULTS
  Median age at diagnosis was 61 years (range: 33-85 y). Tumor stage was pT1N0M0 in 67 patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22 patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and unknown in 9 patients. Tumor VEGF was differentially expressed among different stages (P<0.001) and in low (G1-2) and high (G3-4) Fuhrman grade tumors (P<0.001). No significant differences were found when stratifying by sex (P = 0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical nephrectomy was 161 months (range: 1-366). We observed a significantly longer OS in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206 vs. 65 mo, P<0.001).
  
  
  CONCLUSIONS
  Our data show that tumor cell VEGF expression is significantly associated with tumor stage and Fuhrman grade and is able to predict patient outcome, suggesting a potential use of this parameter in identifying prognostically different patients with ccRCC.
authors: Dipartimento di Scienze Cliniche e Specialistiche, Sezione di Urologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy. Electronic address: d.minardi@univpm.it.
authors: Daniele
authors: D
authors: Minardi
authors: Dipartimento di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Matteo
authors: M
authors: Santoni
authors: Dipartimento di Scienze Cliniche e Molecolari, Sezione di Istologia, Università Politecnica delle Marche, Ancona, Italy.
authors: Guendalina
authors: G
authors: Lucarini
authors: Dipartimento di Scienze Biomediche e Sanità Pubblica, Sezione di Anatomia Patologica ed Istopatologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Roberta
authors: R
authors: Mazzucchelli
authors: Dipartimento di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Luciano
authors: L
authors: Burattini
authors: Dipartimento di Scienze Cliniche e Specialistiche, Sezione di Urologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Alessandro
authors: A
authors: Conti
authors: Dipartimento di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Maristella
authors: M
authors: Bianconi
authors: Dipartimento di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Mario
authors: M
authors: Scartozzi
authors: Dipartimento di Scienze Cliniche e Specialistiche, Sezione di Urologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Giulio
authors: G
authors: Milanese
authors: Dipartimento di Scienze Cliniche e Molecolari, Sezione di Istologia, Università Politecnica delle Marche, Ancona, Italy.
authors: Roberto Di
authors: RD
authors: Primio
authors: Dipartimento di Scienze Biomediche e Sanità Pubblica, Sezione di Anatomia Patologica ed Istopatologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Rodolfo
authors: R
authors: Montironi
authors: Dipartimento di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Stefano
authors: S
authors: Cascinu
authors: Dipartimento di Scienze Cliniche e Specialistiche, Sezione di Urologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors: Giovanni
authors: G
authors: Muzzonigro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Clear cell renal cell carcinoma; Overall survival; Tumor grade; Tumor stage; Vascular endothelial growth factor