THE PROGNOSTIC AND DIFFERENTIAL DIAGNOSTIC VALUE OF CYTOKERATIN 7 AND 19, AND THYROID TRANSCRIPTION FACTOR-1 EXPRESSION IN LUNG NEUROENDOCRINE TUMORS OF VARIOUS GRADES

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Abstract

Background: Neuroendocrine tumors of the lung (NETL) are a wide range of tumors with various malignancy grades and prognosis. Despite their prevalence being 20 to 25% of all lung cancers, many aspects that impact their clinical course and prognosis are not well understood. Aim  – to identify morphological and immunophenotypic characteristics of various NETL types would that more accurately reflect their biological potential and allow for prediction of their unfavorable clinical outcomes. Materials and methods: We performed immunohistochemical assessment of the diagnostic biopsies and surgical specimens from 152 patients with NETL aged 53 ± 13 years and identified 49  typical carcinoids, 32 atypical carcinoids, 60  small cell neuroendocrine carcinomas and 11  large cell neuroendocrine carcinomas, which accounted for 32.2, 21.1, 39.5 and 7.2%, respectively. Markers of neuroendocrine differentiation, such as synaptophysin, chromogranin A  and CD56, as well as cytokeratins 7 and 19, thyroid transcription factor-1 (TTF-1), and Ki67 were used. The results were analyzed with analysis of variance (ANOVA), chi-square test (χ²), and post-hoc comparisons with the Bonferroni correction. Results: Most often, the expression of cytokeratins 7 and 19 was found in large cell neuroendocrine carcinoma (72.7 and 90.9%, respectively), less frequently, in atypical carcinoids and small cell neuroendocrine carcinomas (50 and 53.3%; 41.7 and 64.6% of cases, respectively), whereas in typical carcinoids it was rare (5.9 and 15.9%, respectively). The rates of cytokeratin 7 and 19 expression were significantly lower in the typical carcinoids, compared to the atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р < 0.05, χ²). The expression of cytokeratin 19 was significantly more common for large cell neuroendocrine carcinomas, than for small cell neuroendocrine carcinomas and atypical carcinoids (р < 0.01, χ²). The expression of TTF-1 was very rare in the typical carcinoid cells (6.5% of cases) and significantly more often in atypical carcinoids (61.5%) and in small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (82.7 and 77.8% of cases, respectively). TTF-1 expression was significantly less frequent in typical than in atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р < 0.01, χ²). The mean index of tumor cell proliferation (Ki67) was the lowest in typical carcinoids (2.6%), amounted to 12% in atypical carcinoids, to 44% in large cell neuroendocrine carcinomas and reached the maximum of 61% in small cell neuroendocrine carcinomas. There were significant differences in the mean Ki67 index in the NETL 4 groups (р < 0.001, ANOVA). Conclusion: Expression of TTF-1, cytokeratin 7 and 19 in the neuroendocrine tumors of the lung is characteristic for a  less differentiated cell immunophenotype and allows for identification of the risk group with unfavorable clinical outcome among low-grade typical and atypical carcinoids.

About the authors

L. E. Gurevich

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Author for correspondence.
Email: larisgur@mail.ru
ScD in Biology, Professor, Leading Research Fellow, Department of Pathological Anatomy Russian Federation

N. A. Korsakova

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Senior Research Fellow, Department of Pathological Anatomy Russian Federation

I. A. Voronkova

Endocrinology Research Center; 11 Dmitriya Ul'yanova ul., Moscow, 117036, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Physician, Laboratory of Pathomorphology Russian Federation

I. A. Kazantseva

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Head of Department of Pathological Anatomy Russian Federation

V. E. Ashevskaya

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, Research Fellow, Department of Pathological Anatomy Russian Federation

A. G. Titov

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Leading Research Fellow, Department of Thoracic Surgery Russian Federation

L. M. Kogoniya

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Professor of Chair of Oncology and Thoracic Surgery, Postgraduate Training Faculty Russian Federation

V. S. Mazurin

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Professor, Head of Department of Thoracic Surgery Russian Federation

V. L. Shabarov

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: larisgur@mail.ru
MD, PhD, Physician, Department of Thoracic Surgery Russian Federation

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Copyright (c) 2017 Gurevich L.E., Korsakova N.A., Voronkova I.A., Kazantseva I.A., Ashevskaya V.E., Titov A.G., Kogoniya L.M., Mazurin V.S., Shabarov V.L.

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