Epithelial-mesenchymal transition as a pathogenetic mechanism of development and progression of adenomyosis

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Abstract

BACKGROUND: In recent years, an important role in the pathogenesis of adenomyosis has been assigned to invasive properties of the cells of the basal layer of the endometrium, which provide them with the capacity to grow into the underlying layers of the myometrium.

AIM: The aim of this study was to evaluate the invasive and migratory properties of the ectopic and heterotopic endometrium in patients with adenomyosis.

MATERIALS AND METHODS: We performed clinical, morphological and immunohistochemical analyses of the surgical material of 98 patients with adenomyosis. Immunohistochemical study was carried out according to the standard avidin-biotin method, using mouse monoclonal antibodies to estrogen receptors, matrix metalloproteinase type 9, vimentin, and fibronectin (DAKO, Denmark) as primary immune sera.

RESULTS: The maximum number of estrogen receptors in both the proliferation and secretion phases was found in the endometrial glands and superficially located endometrioid heterotopias. A weaker expression of this marker was also found in the cells of the cytogenic stroma. In the foci of adenomyosis, located in the deep layers of the myometrium, the expression of estrogen receptors in the epithelial and stromal components of heterotopias varied in a wide range from 0 to 100%. The most pronounced expression of matrix metalloproteinase type 9 was characteristic of the epithelial component of superficial endometrioid heterotopias. In the foci of adenomyosis, located in the deep parts of the myometrium, a pronounced expression of matrix metalloproteinase type 9 was preserved in the proliferation phase, and its significant decrease was found in the secretion phase. The glands of the eutopic endometrium were also characterized by a more significant level of matrix metalloproteinase type 9 expression in the proliferation phase in comparison with the secretion phase. A pronounced expression of vimentin was detected in the epithelium of the glands of both superficial and deep foci of adenomyosis, as well as in the eutopic endometrium (100%). In the cytogenic stroma, the largest area of vimentin expression was found in the eutopic endometrium and superficially located endometrioid heterotopias. However, its value significantly decreased in the foci of adenomyosis located in the deep parts of the myometrium. The largest area of fibronectin expression was characteristic of the cytogenic stroma of superficial adenomyosis foci.

CONCLUSIONS: The displacement of elements of the eutopic endometrium into the thickness of the myometrium and further progression of adenomyosis is provided by two parallel pathogenetic mechanisms, namely, invasive growth due to matrix metalloproteinase type 9 activation and epithelial cell migration due to the epithelial-mesenchymal transition.

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About the authors

Victoria 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
ResearcherId: ААВ-2105-2021

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Anna A. Gaidarova

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

Email: a.gaidarova@yandex.ru
ORCID iD: 0000-0003-2391-502X
Russian Federation, Saint Petersburg

Konstantin S. Churkin

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

Email: osia_911@mail.ru
ORCID iD: 0000-0001-6647-8531
Russian Federation, Saint Petersburg

Nikol N. Pertovskaia

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

Email: dr.ramzaeva@mail.ru
ORCID iD: 0000-0001-6849-5335
SPIN-code: 7769-1969
Scopus Author ID: 57838172500
ResearcherId: GLR-8455-2022
Russian Federation, Saint Petersburg

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Supplementary files

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1. Fig. 1. Expression of estrogen receptors: а, endometrium; b, superficial focus of adenomyosis; c, deep focus of adenomyosis. Immunohistochemistry study, zoom ×200

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2. Fig. 2. Matrix metalloproteinase type 9 expression: а, endometrium; b, superficial focus of adenomyosis; c, deep focus of adenomyosis. Immunohistochemistry study, zoom ×200

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3. Fig. 3. Vimentin expression: а, endometrium; b, superficial focus of adenomyosis; c, deep focus of adenomyosis. Immunohistochemistry study, zoom ×200

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4. Fig. 4. Fibronectin expression: а, endometrium; b, superficial focus of adenomyosis; c, deep focus of adenomyosis. Immunohistochemistry study, zoom ×200

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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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.



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