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Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.

ΤίτλοςExpression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.
Publication TypeJournal Article
Year of Publication2017
AuthorsLiontos, 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.
JournalWorld J Urol
Volume35
Issue3
Pagination411-419
Date Published2017 Mar
ISSN1433-8726
Λέξεις κλειδιάAdaptor 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.

DOI10.1007/s00345-016-1890-7
Alternate JournalWorld J Urol
PubMed ID27395374

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