Conservative treatment of atypical hyperplasia and endometrial carcinoma: immunohistochemical aspects
Objective: To test the algorithms of conservative hormonal therapy using buserelin depot and levonorgestrel releasing intrauterine system in women with identified atypical endometrial hyperplasia and/or adenocarcinoma of the uterine body and unrealized fertility.Pashov A.I., Sivova E.N., Volkova L.V., Rachkovskaya V.V.
Materials and methods: The results of the treatment with hormonal drugs were retrospectively evaluated in 52 reproductive-aged patients diagnosed with atypical endometrial hyperplasia ICD-O code 8380/2 (n=40, 77.1%) and well-differentiated (grade 1) endometrioid adenocarcinoma of the uterine body ICD-O code 8380/3 (n=12, 22.9%). The expression of immunohistochemical markers, namely ER, PR, Ki-67, Bcl-2, and E-cadherin, was studied in endometrial samples before and after the treatment.
Results: A complete response to the treatment was noted in 100% of cases. The spontaneous pregnancy occurred in 22 cases (40.4%). The recurrence of the disease was not detected in the patients participating in the study for 15 years, the five-year survival rate was 100%. The study of immunohistochemical markers revealed differences in their expression in endometrial samples of the patients with atypical endometrial hyperplasia and endometrioid adenocarcinoma of the uterine body.
Conclusion: The complex use of gonadotropin-releasing hormone agonists (buserelin depot) with the subsequent insertion of levonorgestrel releasing intrauterine device is an effective method of treating atypical endometrial hyperplasia and stage IA well-differentiated endometrioid adenocarcinoma without invasion into the myometrium in reproductive-aged women with unrealized fertility.
Authors’ contributions: Pashov A.I., Volkova L.V. – developing the concept and design of the study; Sivova E.N. – collecting and processing the material; Pashov A.I., Volkova L.V., Rachkovskaya V.V. – writing the text, editing the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article was prepared without sponsorship.
Ethical Approval: The study was approved by the Ethical Review Board of Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Pashov A.I., Sivova E.N., Volkova L.V., Rachkovskaya V.V. Conservative treatment
of atypical hyperplasia and endometrial carcinoma: immunohistochemical aspects.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (4): 155-160 (in Russian)
https://dx.doi.org/10.18565/aig.2023.18
Keywords
atypical endometrial hyperplasia
well-differentiated endometrioid adenocarcinoma of the uterine body
GnRH agonists
buserelin acetate
levonorgestrel releasing intrauterine device
immunohistochemical markers
References
- Каприн А.Д., Старинский В.В., Шахзадова А.О., ред. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2020. 252с. [Kaprin A.D., Starinsky V.V., Shakhzadova A.O., eds. Malignant neoplasms in Russia in 2019 (morbidity and mortality). Moscow: P.A. Herzen MNROI − branch of the NMRC of Radiology, Ministry of Health of Russia; 2020. 252p. (in Russian)].
- Оразов М.Р., Хамошина М.Б., Муллина И.А., Артеменко Ю.С. Гиперплазия эндометрия – от патогенеза к эффективной терапии. Акушерство и гинекология: новости, мнения, обучение. 2021; 9(3): 21-8. [Orazov M.R., Khamoshina M.B., Mullina I.A., Artemenko Yu.S. Endometrial hyperplasia – from pathogenesis to effective therapy. Obstetrics and Gynecology: News, Opinions, Training. 2021; 9(3): 21-8. (in Russian)].https://dx.doi.org/10.33029/2303-9698-2021-9-3-21-28.
- Hutt S., Tailor A., Ellis P., Michael A., Butler-Manuel S., Chatterjee J. The role of biomarkers in endometrial cancer and hyperplasia: a review of the literature. Acta Oncol. 2019; 58(3): 342-52. https://dx.doi.org/10.1080/0284186X.2018.1540886.
- Бохман Я.В. Руководство по онкогинекологии. СПб.: Фолиант; 2002. 542c. [Bokhman Ya.V. Guide to oncogynecology. St Petersburg: Foliant; 2002. 542p. (in Russian)].
- Новикова О.В., Новикова Е.Г., Лозовая Ю.А., Чулкова О.В., Пронин С.М.Самостоятельная гормонотерапия как альтернатива хирургическому лечению предрака и начального рака эндометрия у пациенток репродуктивного возраста. Онкогинекология. 2015; 3: 25-33. [Novikova O.V., Novikova E.G., Lozovaya Yu.A., Chulkova O.V., Pronin S.M. Self-hormone therapy as an alternative to surgical treatment of precancer and initial endometrial cancer in patients of reproductive age. Oncogynecology. 2015; (3): 25-33. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.1.104-108.
- Пашов А.И., Сивова Е.Н., Метринский Я.Ю. Комбинированное применение агонистов гонадотропин-рилизинг-гормона и внутриматочной левоноргестрел-рилизинг-системы в лечении атипической гиперплазии эндометрия у женщин репродуктивного возраста. Доктор.Ру. 2020; 19(1): 58-61. [Pashov A.I., Sivova E.N., Metrinsky Ya.Yu. Combined use of gonadotropin-releasing hormone agonists and intrauterine levonorgestrel-releasing system in the treatment of atypical endometrial hyperplasia in women of reproductive age. Doctor.Ru. 2020; 19(1): 58-61. (in Russian)].https://dx.doi.org/10.31550/1727-2378-2020-19-1-51-54.
- Westin S.N., Fellman B., Sun C.C., Broaddus R.R., Woodall M.L., Pal N.et al. Prospective study of phase II of the intrauterine device levonorgestrel: a non-surgical approach to complex atypical hyperplasia and early-stage endometrial cancer. Am. J. Obstet. Gynecol. 2021; 224(2): 191.e1-191.e15.https://dx.doi.org/10.1016/j.ajog.2020.08.032.
- Pashov A.I., Tshay V.B., Ionouchene S.V. The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study. Gynecol. Endocrinol. 2012; 28(7): 559-61. https://dx.doi.org/10.3109/09513590.2011.649813.
- Pronin S.M., Novikova O.V., Novikova E.G., Andreeva J.Y. Fertility-sparing treatment of early endometrial cancer and complex atypical hyperplasiain young women of childbearing potential. Int. J. Gynecol. Cancer. 2015; 25(6): 1010-4. https://dx.doi.org/10.1097/IGC.0000000000000467.
- Патент №2428201 Российская Федерация, МПК7А61К38/22, А61К38/21, А61Р35/00. Способ лечения начального рака эндометрия. Пашов А.И., Сивова Е.Н., Цхай В.Б. № 2010131735/15; опубл. 10.09.2011. Бюл. № 25. [Patent No. 2428201 Russian Federation, MPK7A61K38/22, A61K38/21, A61R35/00. A method for the treatment of early endometrial cancer. Pashov A.I., Sivova E.N., Tskhai V.B. No. 2010131735/15; publ. 09/10/2011. Bull. No. 25. (in Russian)].
- Chatzipantelis P., Koukourakis M., Balaska K., Giatromanolaki A. Endometrial stromal expression of ER, PR and B-catenin to differentiate diagnoses of hyperplasia. Int. J. Surg. Pathol. 2022; 30(5): 492-8. https://dx.doi.org/10.1177/10668969211065110.
- Samani S.M., Bojnordi T.E., Zarghampour M., Merat S., Fouladi D.F. Expression of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium: histopathological examination. J. Obstet. Gynaecol. 2018; 38(7): 999-1004. https://dx.doi.org/10.1080/01443615.2018.1437717.
- Travaglino A., Inzani F., Santoro A., Archuolo D., Piermattey A., Paschini S. et al. Metaplastic/reactive changes in the endometrium coexist with endometrial hyperplasia and carcinoma: morphological and immunohistochemical study. Diagnostics (Basel). 2021; 12(1): 63. https://dx.doi.org/10.3390/diagnostics12010063.
- WHO Classification of Tumours Female Genital Tumours. 5th ed. vol. 4: Herrington, C.S., ed. WHO classification of tumours editorial board.WHO: IARC; 2020.
- Nordic immunohistochemical Quality Control (NordiQC). Available at:https://nordiqc.org/index.php
- Данилов Н.В., Андреева Ю.Ю., Завалишина Л.Э., Какеева Т.В., Шикеева А.А., Мальков П.Г., Франк Г.А. Опухоли тела и шейки матки. Морфологическая диагностика и генетика. Руководство. М.: Практическая медицина; 2015. 304c. [Danilov N.V., Andreeva Y.Y., Zavalishina L.E., Kakeeva T.V., Shikeeva A.A., Malkov P.G., Frank G.A. Tumors of the bodt and cervics unerine. Morphological diagnostics and genetics. Guide. Moscow: Practical Medicine; 2015. 304. (in Russian)].
- Felix A.S., Weissfeld J.L., Stone R.A., Bowser R., Chivukula M., Edwards R.P., Linkov F. Factors associated with type I and type II endometrial cancer. Cancer Causes Control. 2010; 21(11):1851-6. https://dx.doi.org/10.1007/s10552-010-96122-8.
- Zidan A.A., Hassan A.A., Seadah Sh.Sh.A., Ibrahim E.H., Attiah S.M. Selected immunohistochemical prognostic factors in endometrial hyperplasia versus carcinoma. J. Am. Sci. 2015; 11(4): 14-22. https://dx.doi.org/10.7860/JCDR/2017/28750.10475.
- Ahmed A.R.H., Muhammad E.M.S. E cadherin and CD10 expression in atypical hyperplastic and malignant endometrial lesions. J. Egypt. Natl. Canc. Instit. 2014; 26(4): 211-7. https://dx.doi.org/10.1016/j.jnci.2014.08.002.
- Carico E., Atlante M., Giarhieri E., Raffa S. E-cadherin and alpha-catenin expression in normal, hyperplastic and neoplastic endometrium. Anticancer Res. 2010; 30(12): 4993-7.
Received 27.01.2023
Accepted 10.04.2023
About the Authors
Alexander I. Pashov, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology of the Medical Institute, Immanuel Kant Baltic Federal University, Ministry of Science and Higher Education of the Russian Federation, +7(911)461-49-98, pachov@mail.ru, https://orcid.org/0000-0001-5346-9185,236016, Russia, Kaliningrad, Botkin str., 4/6.
Evgenia N. Sivova, PhD, Assistant at the Department of Obstetrics and Gynecology, Prof. V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University,
Ministry of Health of the Russian Federation, +7(913)519-22-79, janesivova@gmail.com, 660022, Russia, Krasnoyarsk, Partizan Zheleznyak str., 1.
Larisa V. Volkova, Dr. Med. Sci., Head of the Laboratory of Immunohistochemical, Pathological Anatomical and Clinical Diagnostics, Professor at the Department of Obstetrics and Gynecology of the Medical Institute, Immanuel Kant Baltic Federal University, Ministry of Science and Higher Education of the Russian Federation, +7(921)852-20-42, volkovalr16@gmail.com, https://orcid.org/0000-0003-0938-8577, 236016, Russia, Kaliningrad, Botkin str., 4/6.
Valeriya V. Rachkovskaya, Post-graduate student of the Department of Obstetrics and Gynecology of the Medical Institute, Immanuel Kant Baltic Federal University,
Ministry of Science and Higher Education of the Russian Federation, +7(952)117-48-18, Losevavaleria2104@mail.ru, https://orcid.org/0000-0002-4221-693Х,
236016, Russia, Kaliningrad, Botkin str., 4/6.
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