Русский
Morphologic structure and immunohistochemical analysis of vaginal wall in women with pelvic organ prolapse
DOI: https://dx.doi.org/10.18565/urology.2019.6.12-20
R.V. Vasin, V.B. Filimonov, M.V. Mnikhovich, A.D. Kaprin, A.A. Kostin, I.V. Vasina
1) Department of Urology and Nephrology (Head – MD, prof. Filimonov V.B.) of FGBOU VO Ryazan State Medical University of the Ministry of Health of Russia, Ryazan, Russia; 2) GBU “City clinical hospital No 11” (Chief – MD, prof. Filimonov V.B.), Ryazan, Russia; 3) Department of the Urology and Operative Nephrology with a course of Oncourology of Medical Faculty of the Peoples’ Friendship University of Russia (Head – academician, MD, prof. Kaprin A.D.), Moscow, Russia; 4) Department of Urology, Oncology and Radiology of Postgraduate Faculty of the Peoples’ Friendship University of Russia (Head – corr.-member RAS, MD, prof. Kostin A.A.), Moscow, Russia; 5) Central laboratory of pathologic anatomy of FGBNU Scientific and Research Institute of Human Morphology, Moscow, Russia; 6) Department of Pathologic Anatomy and Clinical Pathologic Anatomy No2 of N.I. Pirogov RNRMU of the Ministry of Health of Russia, Moscow, Russia; 7) Department of Pathologic Anatomy of FGBU National Medical Research Center of Obstetrics, Gynecology and Perinatology named after V.I. Kulakov of the Ministry of Health of Russia, Moscow, Russia
Aim: to study a correlation between clinical stage of pelvic organ prolapse (POP), a histological structure and results of immunohistochemical study of the vaginal wall were evaluated.
Materials and methods. A total of 60 peri- and postmenopausal women (average age 61.9±8.4 years) with POP of stage II–IV, according to the POP-Q classification, or with stress urinary incontinence and cystocele of stage I-II, who undergone to surgical treatment, were included in the study. During a procedure, a biopsy from the anterior vaginal wall was taken. Depending on the stage of POP, patients was divided into two groups. In the group 1, 30 patients with stage I and II of POP were included, while group 2 included 30 women with POP of stage III and more. The control group (group 3) consisted of 20 patients without POP (mean age 63.4±11.0 years) who underwent a hysterectomy due to to other indications.
A histological and immunohistochemical studies of vaginal wall tissue was performed in order to determine the tissue content of collagen type I and III; matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), vimentin and smooth muscle actin.
Results. In contrast to two other groups, in group 2 there were significant changes in the connective tissue. Collagen has a form of fibrous mass with areas of reduced content. In addition, scarring areas with an increase in the content of type III collagen, a decrease in the amount of type I collagen and elastic fibers with significant fragmentation, were seen. Moreover, in patients with severe POP (III–IV), degradation of collagen fibers with a decrease in connective tissue strength and elasticity was detected.
Women with POP had a low ratio of type I:III collagen. Analysis of the collagen content in the vaginal wall in patients with mild POP (I–II) revealed a significant increase in the level of collagen type I (p=0.0003) and a decrease in the content of type III (p=0.045), compared to patients with more severe POP (III–IV).
The level of MMP-1 and MMP-2 in women with POP was higher, than in control group by 1.7 times (p<0.05). The content of TIMP-1 in the group 1 was significantly lower by 1.5 and 2.2 times, compared to group 2 and 3, respectively. An analysis of MMP-1 and MMP-2 concentration in patients of groups 1 and 2 revealed a significant (p=0.04) decrease in their activity in severe POP (III–IV).
In women of the group 2, biopsy of the vaginal wall showed that expression of vimentin and smooth muscle actin in the connective tissue was significantly higher, than in group 1 and 3 (p<0.05). Vimentin expression in the group 2 was 1.4 and 2.6 times higher than in the group 1 and 3, respectively. In the control group, the expression of these markers in the vaginal wall was minimal and focal.
Conclusion. Our data indicate that fibrosis and degradation of the connective tissue in the vaginal wall predominate in POP, and these changes are a consequence, but not a cause of PG. The aggravation of degenerative changes in the connective tissue leads to the progression of POP.
Materials and methods. A total of 60 peri- and postmenopausal women (average age 61.9±8.4 years) with POP of stage II–IV, according to the POP-Q classification, or with stress urinary incontinence and cystocele of stage I-II, who undergone to surgical treatment, were included in the study. During a procedure, a biopsy from the anterior vaginal wall was taken. Depending on the stage of POP, patients was divided into two groups. In the group 1, 30 patients with stage I and II of POP were included, while group 2 included 30 women with POP of stage III and more. The control group (group 3) consisted of 20 patients without POP (mean age 63.4±11.0 years) who underwent a hysterectomy due to to other indications.
A histological and immunohistochemical studies of vaginal wall tissue was performed in order to determine the tissue content of collagen type I and III; matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), vimentin and smooth muscle actin.
Results. In contrast to two other groups, in group 2 there were significant changes in the connective tissue. Collagen has a form of fibrous mass with areas of reduced content. In addition, scarring areas with an increase in the content of type III collagen, a decrease in the amount of type I collagen and elastic fibers with significant fragmentation, were seen. Moreover, in patients with severe POP (III–IV), degradation of collagen fibers with a decrease in connective tissue strength and elasticity was detected.
Women with POP had a low ratio of type I:III collagen. Analysis of the collagen content in the vaginal wall in patients with mild POP (I–II) revealed a significant increase in the level of collagen type I (p=0.0003) and a decrease in the content of type III (p=0.045), compared to patients with more severe POP (III–IV).
The level of MMP-1 and MMP-2 in women with POP was higher, than in control group by 1.7 times (p<0.05). The content of TIMP-1 in the group 1 was significantly lower by 1.5 and 2.2 times, compared to group 2 and 3, respectively. An analysis of MMP-1 and MMP-2 concentration in patients of groups 1 and 2 revealed a significant (p=0.04) decrease in their activity in severe POP (III–IV).
In women of the group 2, biopsy of the vaginal wall showed that expression of vimentin and smooth muscle actin in the connective tissue was significantly higher, than in group 1 and 3 (p<0.05). Vimentin expression in the group 2 was 1.4 and 2.6 times higher than in the group 1 and 3, respectively. In the control group, the expression of these markers in the vaginal wall was minimal and focal.
Conclusion. Our data indicate that fibrosis and degradation of the connective tissue in the vaginal wall predominate in POP, and these changes are a consequence, but not a cause of PG. The aggravation of degenerative changes in the connective tissue leads to the progression of POP.
Keywords: vimentin and smooth muscle actin, epithelial-mesenchymal transition, pelvic organ prolapse, collagen, metalloproteinase
About the Autors
Corresponding author: R.V. Vasin – Ph.D., urologist, associate professor at the Department of Urology and Nephrology of FGBOU VO Ryazan State Medical University of the Ministry of Health of Russia, Deputy Director on the Surgical care and organizational work of GBU “City clinical hospital No 11”, Ryazan, Russia: e-mail: www.rw@mail.ru
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