Expression of the phosphorylated variant of the AKT1-kinase (p-AKT1) in well-differentiated pancreatic neuroendocrine tumors: immunohistochemical evaluation

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Abstract

Background: Well-differentiated pancreatic neuroendocrine tumors (pNETs) represent a group of rare epithelial neoplasms with a highly variable clinical course. AKT1 is one of the most frequently activated protein kinases in pNETs, which promotes the tumor growth and is of interest as a prognostic factor and a target for new treatment approaches.

Aim: To study the expression of the phosphorylated variant of AKT1-kinase (p-AKT1) in primary pNETs and their liver metastases and to correlate the results with various clinical and pathological parameters and the disease prognosis.

Materials and methods: P-AKT1 expression was studied by the immunohistochemical analysis of the primary lesions and liver metastases in 52 pNETs patients.

Results: A high level of cytoplasmic and/or nuclear immunoreactivity was detected in 24/52 of the primary pNETs (46.2%) and in 16/27 of their liver metastases (59.3%). p-AKT1 expression was observed in 3 (21.4%) of NET grade (G) 1, in 14 (46.7%) of NET G2, and in 7 (87.5%) of NET G3. p-AKT1 expression was more frequently identified in pNET G3 category and increased during the tumor progression in metachronous liver metastases, as compared to the corresponding primary tumor. In addition, p-AKT1 positivity was significantly associated with an increase of grade from G1 to G3 (p = 0.004), the Ki-67 index (p = 0.029), the pTNM stage (p = 0.0008), perineural invasion (p = 0.031) and a decrease in disease-free survival (p = 0.05).

Conclusion: The results suggest that p-АКТ1 plays an important role in the pathogenesis of pNETs and may be an additional criterion for assessment of the prognosis and treatment effectiveness in this type of tumors.

About the authors

V. V. Delektorskaya

N.N. Blokhin National Medical Research Centre of Oncology

Author for correspondence.
Email: delektorskaya@yandex.ru

Vera V. Delektorskaya – MD, PhD, Head of Histochemistry and Electron Microscopy Laboratory, Department of Pathology of Human Tumors 

24 Kashirskoe shosse, Moscow, 115478

Russian Federation

O. N. Solov'eva

N.N. Blokhin National Medical Research Centre of Oncology

Email: fake@neicon.ru

Olesya N. Solov'eva – MD, Postgraduate Student, Department of Liver and Рancreatic Tumors

24 Kashirskoe shosse, Moscow, 115478

Russian Federation

G. Yu. Chemeris

N.N. Blokhin National Medical Research Centre of Oncology

Email: fake@neicon.ru

Galina Yu. Chemeris – PhD (in Biology), Senior Research Fellow, Department of Pathology of Human Tumors 

24 Kashirskoe shosse, Moscow, 115478

Russian Federation

Yu. I. Patyutko

N.N. Blokhin National Medical Research Centre of Oncology

Email: fake@neicon.ru

Yuri I. Patyutko – MD, PhD, Professor, Chief Research Fellow, Department of Liver and Рancreatic Tumors 

24 Kashirskoe shosse, Moscow, 115478

Russian Federation

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Copyright (c) 2018 Delektorskaya V.V., Solov'eva O.N., Chemeris G.Y., Patyutko Y.I.

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