Endometrial hyperplasia-related inflammation: its role in the development and progression of endometrial hyperplasia.
BACKGROUND
Endometrial hyperplasia (EH) is one of the most common gynecologic diseases in the world. Different statistical categories implicate an imbalance of estrogens and progestogens in the etiology of this disease. We propose that inflammation also plays a key role in the progression of endometrial hyperplasia.


OBJECTIVE
The aim of this study is to evaluate the role of inflammation in the transformation and progression of endometrial hyperplasia, using local inflammatory cytokines and nonspecific protease levels, CD 45(+) expression, and histological examination.


METHODS
The study included 107 patients (ages 29-49 years) with different forms of endometrial hyperplasia. The enrolled patients were randomized into one of the four groups: normal endometrium (n = 18) as the control group, simple hyperplasia (n = 41), complex hyperplasia without atypia (n = 36), complex atypical hyperplasia or endometrioid adenocarcinoma (n = 12).


METHODS
The following were evaluated for patients with different forms of EH: steroid hormone levels in blood serum and uterine flushings, immunohistochemical estrogen and progesterone receptor expression patterns in the endometrial tissue, CD 45(+) (common leukocyte antigen) expression, the levels of the cytokines IL-1β, IL-6, and TNF-α, and nonspecific proteases and their inhibitors.


RESULTS
The level of estradiol in blood serum and especially in uterine flushings was elevated dramatically in simple EH as compared to that of controls, but there was no significant difference between estradiol levels among the different forms of EH. The estimation of CD 45(+), the levels of the cytokines IL-1β, IL-6, and TNF-α, and the activity of proteases (elastase-like and trypsin-like activities) and their inhibitors showed that levels of nonspecific inflammatory markers increase with EH progression.


CONCLUSIONS
We suggest that the initial responsibility for the development of simple endometrial hyperplasia belongs to systemic hyperestrogenemia and, in particular, local hyperestrogenia, but that the role of inflammatory processes increases in complex and atypical EH. Development of inflammatory changes in endometrial hyperplasia may be considered as a factor in the promotion and progression of pathology, as well as an attributed risk factor for malignancy in endometrial hyperplasia. In this study, we have established a role for CD 45(+) expression cells, non-specific proteases, and the inflammatory cytokines IL-1β, IL-6, and TNF-α in endometrial hyperplasia-related inflammation.
Department of General and Clinical Pathophysiology, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Lenin Blvd, 5/7, Simferopol, 295006, Russia, Republic of Crimea. Kubyshkin_av@mail.ru.
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Kubyshkin
Department of General and Clinical Pathophysiology, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Lenin Blvd, 5/7, Simferopol, 295006, Russia, Republic of Crimea.
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Aliev
Department of General and Clinical Pathophysiology, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Lenin Blvd, 5/7, Simferopol, 295006, Russia, Republic of Crimea.
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Fomochkina
Department of Obstetrics, Gynecology and Perinatology, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Simferopol, Russia, Republic of Crimea.
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Kovalenko
Department of General and Clinical Pathophysiology, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Lenin Blvd, 5/7, Simferopol, 295006, Russia, Republic of Crimea.
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Litvinova
Department of Pathological Anatomy, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Simferopol, Russia, Republic of Crimea.
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Filonenko
Central Clinical Hospital of the Presidential Department of RF, Moscow, Russia.
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Lomakin
Department of Radiodiagnostics and Radiotherapy, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Simferopol, Russia, Republic of Crimea.
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Kubyshkin
Department of Obstetrics, Gynecology and Perinatology, Medical Academy named after S.I. Georgievskiy of the V.I. Vernadsky Crimean Federal University, Simferopol, Russia, Republic of Crimea.
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Karapetian
D000328:Adult; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D010447:Peptide Hydrolases
Carcinogenesis; Cytokines; Endometrial hyperplasia; Inflammation; Nonspecific proteases