@article{3126377,
    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",
    author = "Liontos, M. and Trigka, E.-A. and Korkolopoulou, P. and Tzannis, K. and Lainakis, G. and Koutsoukos, K. and Kostouros, E. and Lykka, M. and Papandreou, C.N. and Karavasilis, V. and Christodoulou, C. and Papatsoris, A. and Skolarikos, A. and Varkarakis, I. and Adamakis, I. and Alamanis, C. and Stravodimos, K. and Mitropoulos, D. and Deliveliotis, C. and Constantinidis, C.A. and Saetta, A. and Patsouris, E. and Dimopoulos, M.Α. and Bamias, A.",
    journal = "World Journal of Urology",
    year = "2017",
    volume = "35",
    number = "3",
    pages = "411-419",
    publisher = "Springer-Verlag",
    issn = "0724-4983, 1433-8726",
    doi = "10.1007/s00345-016-1890-7",
    keywords = "antineoplastic agent;  EIF4EBP1 protein, human;  indole derivative;  MTOR protein, human;  phosphatidylinositol 3 kinase;  phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase;  phosphatidylinositol 4,5 bisphosphate 3 kinase;  phosphoprotein;  PIK3CG protein, human;  PIK3R1 protein, human;  protein kinase B;  PTEN protein, human;  pyrrole derivative;  S6 kinase;  signal transducing adaptor protein;  sunitinib;  target of rapamycin kinase;  vasculotropin A;  VEGFA protein, human, adult;  aged;  Carcinoma, Renal Cell;  female;  human;  immunohistochemistry;  Kidney Neoplasms;  male;  metabolism;  middle aged;  pathology;  prognosis;  retrospective study;  secondary;  survival rate;  very elderly, Adaptor Proteins, Signal Transducing;  Adult;  Aged;  Aged, 80 and over;  Antineoplastic Agents;  Carcinoma, Renal Cell;  Class Ib Phosphatidylinositol 3-Kinase;  Female;  Humans;  Immunohistochemistry;  Indoles;  Kidney Neoplasms;  Male;  Middle Aged;  Phosphatidylinositol 3-Kinases;  Phosphoproteins;  Prognosis;  Proto-Oncogene Proteins c-akt;  PTEN Phosphohydrolase;  Pyrroles;  Retrospective Studies;  Ribosomal Protein S6 Kinases, 70-kDa;  Survival Rate;  TOR Serine-Threonine Kinases;  Vascular Endothelial Growth Factor A",
    abstract = "Purpose: 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). Conclusion: 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. © 2016, Springer-Verlag Berlin Heidelberg."
}