TY - JOUR
TI - Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients
AU - Liontos, M.
AU - Trigka, E.-A.
AU - Korkolopoulou, P.
AU - Tzannis, K.
AU - Lainakis, G.
AU - Koutsoukos, K.
AU - Kostouros, E.
AU - Lykka, M.
AU - Papandreou, C.N.
AU - Karavasilis, V.
AU - Christodoulou, C.
AU - Papatsoris, A.
AU - Skolarikos, A.
AU - Varkarakis, I.
AU - Adamakis, I.
AU - Alamanis, C.
AU - Stravodimos, K.
AU - Mitropoulos, D.
AU - Deliveliotis, C.
AU - Constantinidis, C.A.
AU - Saetta, A.
AU - Patsouris, E.
AU - Dimopoulos, M.Α.
AU - Bamias, A.
JO - World Journal of Urology
PY - 2017
VL - 35
TODO - 3
SP - 411-419
PB - Springer-Verlag
SN - 0724-4983, 1433-8726
TODO - 10.1007/s00345-016-1890-7
TODO - 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
TODO - 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.
ER -