Human leukocyte antigen, isotype DR (HLA-DR) expression in the normal endometrium and in endometrial pathology

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Abstract

BACKGROUND: Human leukocyte antigen, isotype DR (HLA-DR) expression is associated with inflammatory and autoimmune diseases. It is also found on the surface of tumor cells. The role of HLA-DR in endometrial pathology has not been sufficiently studied.

AIM: The aim of this study was to determine HLA-DR expression features in the endometrium under normal and pathological conditions.

MATERIALS AND METHODS: We performed immunohistochemical examination of endometrial biopsy specimens, namely, 18 cases of endometrioid carcinomas, 139 cases of chronic endometritis, and 37 cases of endometrial polyps. The control group included 50 cases of the endometrium without pathology. Positive HLA-DR expression was detected as brown staining of varying intensity of immune cells of the cytogenic stroma, as well as the cytoplasm and membranes of endometrial epithelial cells. The average number of positively stained stromal cells in ten visual fields was counted. HLA-DR expression in the cytoplasm and on the membrane of endometrial epithelial cells was assessed semi-quantitatively as weak (low) (with staining up to 50% of the glands) or pronounced (high) (with staining more than 50% of the glands).

RESULTS: HLA-DRim expression was detected on immune cells of the cytogenic stroma of the endometrium in all of the study groups. HLA-DR expression in the endometrial epithelium was characterized by two main immunophenotypes — negative and positive. Negative HLA-DR expression was found in 55.6% of endometrial cancer cases, in 25.2% of chronic endometritis cases, in 27.7% of endometrial polyp cases, and in all cases of the normal endometrium. The positive HLA-DR (high) immunophenotype was found in 21.6% of chronic endometritis cases, in 28.6% of endometrial polyp cases, and in 16.7% of endometrial cancer cases. Pronounced HLA-DR expression in the epithelium was associated with a high HLA-DR level in the cytogenic stroma and a significantly frequent detection of HLA-DR+ lymphoid follicles in endometrial cancer. The positive HLA-DR (low) immunophenotype was established in 51.8% of chronic endometritis cases and in 27.8% of endometrial polyp cases, and in 27.7% of endometrial cancer cases, and was associated with low HLA-DR levels in the stroma.

CONCLUSIONS: The revealed heterogeneity of HLA-DR expression in chronic inflammation and endometrial cancer allows for distinguishing two main immunophenotypes of endometrial cancer, namely, with negative and positive HLA-DR expression. HLA-DR may be an early predictor of adverse background endometrium and endometrial cancer. The positive HLA-DR immunophenotype of endometrial cancer probably indicates a specific mechanism of carcinogenesis associated with chronic inflammation and requires further comprehensive clinical, morphological and molecular genetic research.

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About the authors

Vera N. Ellinidi

North-Western State Medical University named after I.I. Mechnikov; N.N. Petrov National Medical Research Center of Oncology

Email: ellinidiv@rambler.ru
ORCID iD: 0000-0002-7091-3142

MD, Cand. Sci. (Medicine)

Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015; Saint Petersburg

Elizaveta A Smaglenko

North-Western State Medical University named after I.I. Mechnikov

Email: veta728@bk.ru
ORCID iD: 0009-0006-9196-9205
Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015

Viktoria A. Pechenikova

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: p-vikka@mail.ru
ORCID iD: 0000-0001-5322-708X
SPIN-code: 9603-5645

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015

Igor A. Samusenko

A.M. Nikiforov All-Russian Center for Emergency and Radiation Medicine

Email: egors_2000@mail.ru
ORCID iD: 0000-0003-0622-3515
SPIN-code: 6669-5602

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Maxim V. Bunyakov

A.M. Nikiforov All-Russian Center for Emergency and Radiation Medicine

Email: bunyakovmaxim@gmail.com
ORCID iD: 0009-0000-9820-2054
SPIN-code: 2531-5016

MD

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Normal endometrial epithelium: negative expression of HLA-DR in the cytoplasm and on the membrane of endometrial epithelial cells, expression of HLA-DR of cytogenic stroma immune cells, zoom ×200

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3. Fig. 2. Chronic endometritis: positive expression of HLA-DR in the cytoplasm and on the membrane of endometrial epithelial cells, expression of HLA-DR of cytogenic stroma immune cells, zoom ×200

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4. Fig. 3. Endometrioid carcinoma: positive expression of HLA-DR in the cytoplasm and on the membrane of endometrial epithelial cells, expression of HLA-DR of cytogenic stroma immune cells, zoom ×200

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5. Fig. 4. Dynamics of expression human leukocyte antigen, isotype DR (HLA-DR) immune cells depending on HLA-DR expression on epithelial cells in various endometrial pathologies

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия Эл № 77 - 6389
от 15.07.2002 г.