REMODELING OF AN ENDOCERVICAL STEM CELL NICHE IN HPV-ASSOCIATED PRECANCER AND MICROINVASIVE CANCER OF THE CERVIX UTERI


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Objective. To study the morphological manifestations of and the molecular mechanisms for remodeling of an endocervical stem cell niche (ESCN) in human papillomavirus (HPV)-associated precancer and microinvasive cancer of the cervix uteri (CCU). Materials and methods. Retrospective clinicomorphological and molecular biological studies were conducted using cytological, biopsy, and intraoperative specimens from 251 patients with various HPV-associated abnormalities of the cervix uteri: flat condyloma (n=80), CIN I (n=47), CIN II-III (n=110), and microinvasive carcinoma (n=14). Immunocytochemical and immunohistochemical studies were performed. The markers р16INK4a, Ki-67, СХ17, Oct-4, SMA, CD34, MMP2, and Vimentin were determined. Real-time polymerase chain reaction (PCR) and in situ PCR were carried out to identify 14 high-risk HPV types in 79 women. Results. HPV infection causes ESCN remodeling, giving rise to abnormal epithelial repair, precancer and cancer of the cervix uteri. A key role in these processes is played by viral integration with tissue epithelial stem cells and decompensated progenetic mesenchymal cell function. The development of flat CCU is accompanied by the emergence of cancer cell clones with the signs of stemness. Conclusion. Comprehensive female examination comprising cytology with HPV testing and evaluation of the status of ESCN should be recommended to improve the early diagnosis and prevention of CCU.

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作者简介

E. KOGAN

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: koganevg@gmail.com

N. FAIZULLINA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: nafisa05@inbox.ru

S. DEMURA

I.M. Sechenov First Moscow State Medical University

Email: sophja_demoura@mail.ru

T. DEMURA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: demura-t@yandex.ru

A. ISRAILOVA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: angel_55@list.ru

A. KOZACHENKO

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: a_kozachenko@oparina4.ru

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