STEROID HORMONE RECEPTOR STATUS OF ENDOMETRIAL ADENOCARCINOMAS AS AN IMPORTANT PROGNOSTIC INDICATOR IN POSTMENOPAUSAL PATIENTS
Keywords:
endometrial cancer, estrogen and progesterone receptors, postmenopausal period, clinico-morphological features.Abstract
Summary. The aim of the study was to compare the
number of cells expressing estrogen receptor alpha (ERα)
and progesterone receptor (PR) in endometrial cancer (EC) patients with different menstrual status considering clinico-morphological features of tumors. Object and methods: 99 surgical specimens of EC patients
with stage I–II, aged from 26 to 76 years (average age
56.8 ± 0.8 years) were investigated using morphological, immunohistochemical and statistical methods. Results: It was found that 73.5% of investigated endometrial tumors had positive (ERα+PR+) receptor phenotype
and 11.3% were characterized by negative (ERαPR-
)
receptor phenotype. It was determined that such indicators of EC progression as high proliferative activity, deep
myometrial invasion, low level of differentiation and low
5-years survival of patients correlated with the reduced
number of cells expressing ERα and PR and negative receptor phenotype. It was shown that in postmenopausal
EC patients increased number of poorly differentiated
adenocarcinoma and tumors with deep myometrial invasion was observed compared to EC patients with retained menstrual function, in whose tumors with high/
moderate degree of differentiation and shallow myometrial invasion dominated. Conclusion: endometrial adenocarcinoma of postmenopausal EC patients are
characterized by generally low level of differentiation,
high proliferative potential, deep myometrial invasion,
a small number of cells expressing steroid hormone receptors (ERα and PR) and negative phenotype receptor
(ERα−PR−) in contrast to these parameters in patients
with retained menstrual function.
References
Рак в Україні, 2013–2014. Захворюваність, смертність, показники діяльності онкологічної служби. Бюл Нац канцерреєстру України, 2015; (16): 106 с.
Васильев Д.А. Активность пероксидазы в ткани тела матки: связь с эстрогинезацией и клинико-морфологическими особенностями опухоли [Автореф дис… канд мед наук] СПб. 2003.
Чернышова АЛ, Коломиец ЛА, Стуканова СЛ. Особенности гормонального фона и рецепции половых гормонов у больных с гиперпластическими процессами и раком эндометрия. Бюл сиб мед 2012; 6: 172–6.
Bolton JL, Thatcher GR. Potential mechanisms of estrogen quinone carcinogenesis. Chem Res Toxicol 2008; 21 (1): 93–101.
Rizner TL. Estrogen biosynthesis, phase I and phase II metabolism, and action in endometrial cancer. Mol Cell Endocrinol 2013; 381: 124–39.
Tashiro H, Katabuchi H. The relationship between estrogen and genes in the molecular pathogenesis of endometrial cancer. Curr Obstet Gynecol Rep 2014; 3: 9–17.
Weihua Z, Saji S, Mäkinen S, et al. Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus. Proc Natl Acad Sci USA 2000; 97: 5936–41.
Park CK, Apte S, Acs G, Harris EER. Abeloff’s clinical oncology. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Cancer of the endometrium. 4th ed. Chapter 92, Philadelphia, PA: Churchill Livingstone Elsevier, 2008: 1793–825.
Nishimukai A, Yagi T, Yanai A, et al. High Ki-67 expression and low progesterone receptor expression could independently lead to a worse prognosis for postmenopausal patients with estrogen receptor-positive and HER2-negative breast cancer. Clin Breast Cancer 2015; 15 (3): 204–11.
Ito K, Utsunomiya H, Yaegashi N, Sasano H. Biological roles of estrogen and progesterone in human endometrial carcinoma — new developments in potential endocrine therapy for endometrial cancer. Endocr J 2007; 54 (5): 667–79.
Rizner TL. Estrogen biosynthesis, phase I and phase II metabolism, and action in endometrial cancer. Mol Cell Endocrinol 2013; 381 (1–2): 124–39.
Kim JJ, Sefton EC, Bulun SE. Progesterone receptor action in leiomyoma and endometrial cancer. Prog Mol Biol Transl
Sci 2009; 87: 53–85.
Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev 2013; 34 (1): 130–62.
Коваль ВД, Кондакова ИВ, Спирина ЛВ. Роль убиквитин-протеасомной системы в развитии рака эндометрия. Вопр онкол 2012; 58 (4): 473–80.
Берштейн ЛМ, Цырлина ЕВ, Коваленко ИГ и др. Сравнительные особенности гормонально-метаболического статуса убольных срецепторнегативными новообразованиями молочной железы и эндометрия. Вопр онкол 2003; 49: 716–4.
Конар РС, Русін АВ, Рішко МФ та ін. Експресія стероїдних гормонів як фактор прогнозу у хворих на рак молочної залози. Онкология 2008; 10 (1): 55–7.
Buchynska LG, Iurchenko NP, Grinkevych VN, et al. Expression of the estrogen and progesterone receptors as prognostic factor in serous ovarian cancers. Exp Oncol 2009; 31 (1): 48–51.
Jarzabek K, Koda M, Walentowicz-Sadlecka M, et al. Altered expression of ERs, aromatase, and COX2 connected to estrogen action in type 1 endometrial cancer biology. Tumor Biol 2013; 34 (6): 4007–16.
Берштейн ЛМ. Рак эндометрия, э стр огены и метаболический синдром: сценарий усложняется. Вопр онкол 2014; 60 (3): 54–62.
Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO Classification of tumours of the female reproductive organs (IARC WHO Classification of Tumours) 4th Edition Series: IARC Press, 2014. 307 p.
Srijaipracharoen S, Tanjitgamol S, Tanyanich S, et al. Expression of ER, PR, and Her-2/neu in endometrial cancer: a clinicopathological study. Asian Pac J Cancer Prev 2010; 11 (1): 215–20.
Kreizman-Shefer H, Pricop J, Goldmam S, et al. Distribution of estrogen and progesterone receptors isoforms in endometrial cancer. Dianostic Pathol 2014; 9: 77.
Parise CA, Bauer KR, Brown MM, Caggiano V. Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999–2004. Breast J 2009; 15 (6): 593–602.
Huvila J, Talve L, Carpén O, et al. Progesterone receptor negativity is an independent risk factor for relapse in patients with early stage endometrioid endometrial adenocarcinoma. Gynecol Oncol 2013; 130 (3): 463–9.
Tangen IL, Werner HM, Berg A, Halle MK, et al. Loss of progesterone receptor links to high proliferation and increases from primary to metastatic endometrial cancer lesions. Eur J Cancer 2014; 50 (17): 3003–10.
Backes FJ, Walker CJ, Goodfellow PJ, et al. Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer. Gynecol Oncol 2016; 141 (2): 312–7.
Sivridis E, Giatromanolaki A. The pathogenesis of endometrial carcinomas at menopause: facts and figures. J Clin Pathol 2011; 64: 553–60.
Воробьева ЛИ, Свинцицкий ВС, Ткаля ЮГ. Гормональный канцерогенез и обоснование применения гормональной терапии в лечении больных раком яичника. Клин Онкол 2013; 1: 58–64.
Ашрафян ЛА, Киселев ВИ. Опухоли репродуктивных органов (этиология и патогенез). М.: Димитрейд График Групп, 2007. 214 с.
Sissung TM, Price DK, Sparreboom A, Figg WD. Pharmacogenetics and regulation of human cytochrome P450 1B1: implications in hormone-mediated tumor metabolism and a novel target for therapeutic intervention. Mol Cancer Res 2006; 4 (3): 135–50.
