Τίτλος:
Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Liontos, M.
Trigka, E.-A.
Korkolopoulou, P.
Tzannis, K.
Lainakis, G.
Koutsoukos, K.
Kostouros, E.
Lykka, M.
Papandreou, C.N.
Karavasilis, V.
Christodoulou, C.
Papatsoris, A.
Skolarikos, A.
Varkarakis, I.
Adamakis, I.
Alamanis, C.
Stravodimos, K.
Mitropoulos, D.
Deliveliotis, C.
Constantinidis, C.A.
Saetta, A.
Patsouris, E.
Dimopoulos, M.Α.
Bamias, A.
Περιοδικό:
World Journal of Urology
Λέξεις-κλειδιά:
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
DOI:
10.1007/s00345-016-1890-7
