title: Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.
abstract: OBJECTIVE
  To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components.
  
  
  METHODS
  The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival.
  
  
  RESULTS
  VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001).
  
  
  CONCLUSIONS
  Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece. mliontos@gmail.com.
authors.forename: Michalis
authors.initials: M
authors.lastname: Liontos
authors.affiliation: 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Eleni-Andriana
authors.initials: EA
authors.lastname: Trigka
authors.affiliation: 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Kimon
authors.initials: K
authors.lastname: Tzannis
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Lainakis
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Koutsoukos
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.
authors.forename: Efthymios
authors.initials: E
authors.lastname: Kostouros
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Lykka
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Karavasilis
authors.affiliation: 2nd Department of Medical Oncology, "Metropolitan" Hospital, Piraeus, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Christodoulou
authors.affiliation: 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatsoris
authors.affiliation: 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Skolarikos
authors.affiliation: 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Varkarakis
authors.affiliation: 1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Adamakis
authors.affiliation: 1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Alamanis
authors.affiliation: Hellenic GenitoUrinary Cancer Group, Athens, Greece.|1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stravodimos
authors.affiliation: Hellenic GenitoUrinary Cancer Group, Athens, Greece.|1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Dionysios
authors.initials: D
authors.lastname: Mitropoulos
authors.affiliation: 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Deliveliotis
authors.affiliation: Hellenic GenitoUrinary Cancer Group, Athens, Greece.|1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Constantinos A
authors.initials: CA
authors.lastname: Constantinidis
authors.affiliation: 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Angelica
authors.initials: A
authors.lastname: Saetta
authors.affiliation: 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Meletios Α
authors.initials: MΑ
authors.lastname: Dimopoulos
authors.affiliation: Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.|Hellenic GenitoUrinary Cancer Group, Athens, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D018797:Cell Cycle Proteins; D058543:Class Ia Phosphatidylinositol 3-Kinase; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D000077210:Sunitinib; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D058543:Class Ia Phosphatidylinositol 3-Kinase; D058544:Class Ib Phosphatidylinositol 3-Kinase; D007211:Indoles; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D011758:Pyrroles; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C087000:EIF4EBP1 protein, human; C467484:VEGFA protein, human; C588001:PIK3R1 protein, human; C546842:MTOR protein, human; C546760:PIK3CG protein, human; C494929:PTEN protein, human
keywords: Sunitinib; VEGF; mRCC; mTOR