To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components.
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.
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).
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.
World journal of urology. 2016 Jul 09 [Epub ahead of print]
Michalis Liontos, Eleni-Andriana Trigka, Penelope Korkolopoulou, Kimon Tzannis, Giorgos Lainakis, Konstantinos Koutsoukos, Efthymios Kostouros, Maria Lykka, Christos N Papandreou, Vassilis Karavasilis, Christos Christodoulou, Athanasios Papatsoris, Andreas Skolarikos, Ioannis Varkarakis, Ioannis Adamakis, Christos Alamanis, Konstantinos Stravodimos, Dionysios Mitropoulos, Charalambos Deliveliotis, Constantinos A Constantinidis, Angelica Saetta, Efstratios Patsouris, Meletios Α Dimopoulos, Aristotelis Bamias
Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece. ., 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece., Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece., Department of Medical Oncology, "Papageorgiou" Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece., 2nd Department of Medical Oncology, "Metropolitan" Hospital, Piraeus, Greece., 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., 1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., 1st Department of Urology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Hellenic GenitoUrinary Cancer Group, Athens, Greece., Hellenic GenitoUrinary Cancer Group, Athens, Greece., 2nd Department of Urology, Sismanoglio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Hellenic GenitoUrinary Cancer Group, Athens, Greece., 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., 1st Department of Pathology, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece., Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 V.Sofias Ave, 11528, Athens, Greece.