DOI: https://doi.org/10.18370/2309-4117.2020.54.39-45

Immunohistochemical features of benign endometrial hyperplasia in premenopausal women

Н. М. Рожковська, І. С. Ломакіна

Abstract


Hyperproliferative diseases of the endometrium play an important role in the structure of gynecological pathology, which are a spectrum of irregular morphological changes. Particularly difficult is evaluation of the phenotypic characteristics of the endometrium hyperplastic processes (EHP) in premenopausal women in the presence of an unstable menstrual cycle. Diagnosis and EHP prognosis remains a difficult task given that it can occur as focal or diffuse lesions with various structural and cytological differences.

Objective of the study: to evaluate the immunohistochemical features (phenotypic variants) of benign endometrial hyperplasia in premenopausal women.

Material and methods. 33 premenopausal women with abnormal uterine bleeding and verified benign endometrial hyperplasia were examined. Expression of the α-receptors for estrogens type 1 (ER1), progesterone receptors and Ki-67 nuclear protein in the endometrium stroma and glands was analyzed. Micromorphometry was performed and the D-score was calculated.

Results. Prevalence of comorbid lesions in patients was the combination of endometrial hyperplasia and fibroids (51.4%), cases of abnormal uterine bleedings against submucosal fibroids (13.5%), endometrial polyps (8.1%), combinations of EHP and peritoneal endometriosis (10.8%), adenomyosis and myoma (8.1%), or other combinations of endometrial and myometrial proliferative pathology. D-score for surgery averaged 1.78 ± 0.11 indicating a low risk of malignancy. There were changes after treatment in the quantitative presentation of the studied proteins in stroma and endometrial glands. Thus, before treatment in the glands was determined up to 100% of cells containing ER1 in large quantities, while after treatment their number decreased by an average of 20%. Similar dynamics was observed with progesterone receptors activity.

Conclusions. The main prognostic significant phenotypes of endometrial proliferative pathology have been identified. After removing of pathologically chanced endometrium and subsequent treatment with dydrogesterone during 6 months there is prognostically positive decreasing in the ER1 density as well as the Ki-67 protein expression

Keywords


benign endometrial hyperplasia; adenomyosis; abnormal uterine bleedings; phenotype; receptors; biomarkers; diagnosis; dydrogesterone

References


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Chiu, H.C., Li, C.J., Yiang, G.T., et al. “Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis.” J Clin Med 8.4 (2019).

Giuntoli, R.L. 2nd, Gerardi, M.A., Yemelyanova, A.V., et al. “Stage I noninvasive and minimally invasive uterine serous carcinoma: comprehensive staging associated with improved survival.” Int J Gynecol Cancer 22.2 (2014): 273–9.

Jia, M., Sun, P.L., Gao, H. “Uterine lesions with sex cord-like architectures: a systematic review.” Diagn Pathol 14.1 (2019): 129.

Lacheta, J. “Uterine adenomyosis: pathogenesis, diagnostics, symptomatology and treatment.” Ceska Gynekol 84.3 (2019): 240–6.

MacKintosh, M.L., Crosbie, E.J. “Prevention Strategies in Endometrial Carcinoma.” Curr Oncol Rep 20.12 (2018): 101.

Munro, M.G. “Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity.” Fertil Steril 111.4 (2019): 629–40.

Nijkang, N.P., Anderson, L., Markham, R., Manconi, F. “Endometrial polyps: Pathogenesis, sequelae and treatment.” SAGE Open Med 7 (2019).

Raffone, A., Travaglino, A., Saccone, G., et al. “Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta-analysis.” Acta Obstet Gynecol Scand 98.8 (2019): 976–87.

Salazar, C.A., Isaacson, K.B. “Office Operative Hysteroscopy: An Update.” J Minim Invasive Gynecol 25.2 (2018): 199–208.

Sanderson, P.A., Critchley, H.O., Williams, A.R., et al. “New concepts for an old problem: the diagnosis of endometrial hyperplasia.” Hum Reprod Update 23.2 (2017): 232–54.

Yang, S., Wang, H., Li, D., Li, M. “Role of Endometrial Autophagy in Physiological and Pathophysiological Processes.” J Cancer 10.15 (2019): 3459–71.

Vannuccini, S., Petraglia, F. “Recent advances in understanding and managing adenomyosis.” F1000Res 8 (2019): F1000 Faculty Rev-283. DOI: 10.12688/f1000research.17242.1

Bajwa, P., Nielsen, S., Lombard, J.M., et al. “Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice.” Oncotarget 8.5 (2017): 7265–75. DOI: 10.18632/oncotarget.13919

Hosseini Nasab, S., Jooya, N., Esmaeili, A., et al. “Using Pyruvate Kinase as a Predictor for Patient With Endometrial Cancer Having Complex Hyperplasia With Atypia to Prevent Hysterectomy and Preserve Fertility: Retrospective Immunohistochemical Study.” Reprod Sci 25.8 (2018): 1286–91. DOI: 10.1177/1933719117741371

Yin, M., Zhou, H.J., Lin, C., et al. “CD34 Stromal Stem Cells Contribute to Endometrial Regeneration and Repair.” Cell Rep 27.9 (2019): 2709–24.e3. DOI: 10.1016/j.celrep.2019.04.088

Owuor, T.O., Reid, M., Reschke, L., et al. “Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.” PLoS One 13.5 (2018): e0186390. DOI: 10.1371/journal.pone.0186390

Carmina, E., Guastella, E., Longo, R.A. “Advances in the Diagnosis and Treatment of PCOS.” Curr Pharm Des 22.36 (2016): 5508–14. DOI: 10.2174/13816128226661 60719105808

Kurdoglu, M., Kucukaydin, Z., Kurdoglu, Z., et al. “Expression of Laminin Receptor 1 in Normal, Hyperplastic, and Malignant Endometrium.” Int J Gynecol Pathol 38.4 (2019): 326–34. DOI: 10.1097/PGP.0000000000000535

Russo, M., Broach, J., Sheldon, K., et al. “Clonal evolution in paired endometrial intraepithelial neoplasia/atypical hyperplasia and endometrioid adenocarcinoma.” Hum Pathol 67 (2017): 69–77. DOI: 10.1016/j.humpath.2017.07.003

Lauritsen, C.G., Chua, A.L., Nahas, S.J. “Current Treatment Options: Headache Related to Menopause-Diagnosis and Management.” Curr Treat Options Neurol 20.4 (2018): 7. DOI: 10.1007/s11940-018-0492-7

Bulsa, M., Urasińska, E. “Triple negative endometrial cancer.” Ginekol Pol 88.4 (2017): 212–4. DOI: 10.5603/GP.a2017.0040

Goldstein, S.R., Lumsden, M.A. “Abnormal uterine bleeding in perimenopause.” Climacteric 20.5 (2017): 414–20. DOI: 10.1080/13697137.2017.1358921

Bosteels, J., van Wessel, S., Weyers, S., et al. “Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities.” Cochrane Database Syst Rev 12 (2018): CD009461. DOI: 10.1002/14651858.CD009461.pub4

Gordts, S., Grimbizis, G., Campo, R. “Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis.” Fertil Steril 109.3 (2018): 380–8.e1. DOI: 10.1016/j. fertnstert.2018.01.006


GOST Style Citations


1.      Amălinei, C., Păvăleanu, I., Grigoraş, A., et al. “The endometrial regeneration frontiers: from mechanisms to applications in regenerative medicine.” Rom J Morphol Embryol 59.2 (2018): 407–25.

2.      Chiu, H.C., Li, C.J., Yiang, G.T., et al. “Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis.” J Clin Med 8.4 (2019).

3.      Giuntoli, R.L. 2nd, Gerardi, M.A., Yemelyanova, A.V., et al. “Stage I noninvasive and minimally invasive uterine serous carcinoma: comprehensive staging associated with improved survival.” Int J Gynecol Cancer 22.2 (2014): 273–9.

4.      Jia, M., Sun, P.L., Gao, H. “Uterine lesions with sex cord-like architectures: a systematic review.” Diagn Pathol 14.1 (2019): 129.

5.      Lacheta, J. “Uterine adenomyosis: pathogenesis, diagnostics, symptomatology and treatment.” Ceska Gynekol 84.3 (2019): 240–6.

6.      MacKintosh, M.L., Crosbie, E.J. “Prevention Strategies in Endometrial Carcinoma.” Curr Oncol Rep 20.12 (2018): 101.

7.      Munro, M.G. “Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity.” Fertil Steril 111.4 (2019): 629–40.

8.      Nijkang, N.P., Anderson, L., Markham, R., Manconi, F. “Endometrial polyps: Pathogenesis, sequelae and treatment.” SAGE Open Med 7 (2019).

9.      Raffone, A., Travaglino, A., Saccone, G., et al. “Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta-analysis.” Acta Obstet Gynecol Scand 98.8 (2019): 976–87.

10.    Salazar, C.A., Isaacson, K.B. “Office Operative Hysteroscopy: An Update.” J Minim Invasive Gynecol 25.2 (2018): 199–208.

11.    Sanderson, P.A., Critchley, H.O., Williams, A.R., et al. “New concepts for an old problem: the diagnosis of endometrial hyperplasia.” Hum Reprod Update 23.2 (2017): 232–54.

12.    Yang, S., Wang, H., Li, D., Li, M. “Role of Endometrial Autophagy in Physiological and Pathophysiological Processes.” J Cancer 10.15 (2019): 3459–71.

13.    Vannuccini, S., Petraglia, F. “Recent advances in understanding and managing adenomyosis.” F1000Res 8 (2019): F1000 Faculty Rev-283. DOI: 10.12688/f1000research.17242.1

14.    Bajwa, P., Nielsen, S., Lombard, J.M., et al. “Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice.” Oncotarget 8.5 (2017): 7265–75. DOI: 10.18632/oncotarget.13919

15.    Hosseini Nasab, S., Jooya, N., Esmaeili, A., et al. “Using Pyruvate Kinase as a Predictor for Patient With Endometrial Cancer Having Complex Hyperplasia With Atypia to Prevent Hysterectomy and Preserve Fertility: Retrospective Immunohistochemical Study.” Reprod Sci 25.8 (2018): 1286–91. DOI: 10.1177/1933719117741371

16.    Yin, M., Zhou, H.J., Lin, C., et al. “CD34 Stromal Stem Cells Contribute to Endometrial Regeneration and Repair.” Cell Rep 27.9 (2019): 2709–24.e3. DOI: 10.1016/j.celrep.2019.04.088

17.    Owuor, T.O., Reid, M., Reschke, L., et al. “Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.” PLoS One 13.5 (2018): e0186390. DOI: 10.1371/journal.pone.0186390

18.    Carmina, E., Guastella, E., Longo, R.A. “Advances in the Diagnosis and Treatment of PCOS.” Curr Pharm Des 22.36 (2016): 5508–14. DOI: 10.2174/13816128226661 60719105808

19.    Kurdoglu, M., Kucukaydin, Z., Kurdoglu, Z., et al. “Expression of Laminin Receptor 1 in Normal, Hyperplastic, and Malignant Endometrium.” Int J Gynecol Pathol 38.4 (2019): 326–34. DOI: 10.1097/PGP.0000000000000535

20.    Russo, M., Broach, J., Sheldon, K., et al. “Clonal evolution in paired endometrial intraepithelial neoplasia/atypical hyperplasia and endometrioid adenocarcinoma.” Hum Pathol 67 (2017): 69–77. DOI: 10.1016/j.humpath.2017.07.003

21.     Lauritsen, C.G., Chua, A.L., Nahas, S.J. “Current Treatment Options: Headache Related to Menopause-Diagnosis and Management.” Curr Treat Options Neurol 20.4 (2018): 7. DOI: 10.1007/s11940-018-0492-7

22.     Bulsa, M., Urasińska, E. “Triple negative endometrial cancer.” Ginekol Pol 88.4 (2017): 212–4. DOI: 10.5603/GP.a2017.0040

23.     Goldstein, S.R., Lumsden, M.A. “Abnormal uterine bleeding in perimenopause.” Climacteric 20.5 (2017): 414–20. DOI: 10.1080/13697137.2017.1358921

24.     Bosteels, J., van Wessel, S., Weyers, S., et al. “Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities.” Cochrane Database Syst Rev 12 (2018): CD009461. DOI: 10.1002/14651858.CD009461.pub4

25.     Gordts, S., Grimbizis, G., Campo, R. “Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis.” Fertil Steril 109.3 (2018): 380–8.e1. DOI: 10.1016/j. fertnstert.2018.01.006





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