RECEPTORS OF ENDOMETRIUM IN PREMENOPAUSAL WOMEN WITH DIFFERENT MORPHOTYPES OF ENDOMETRIAL HYPERPLASIA

Abstract

Introduction. Endometrial hyperplasia is a commonproblem among premenopausal women. There are nonatypical (EH) and atypical (AH) morphotypes according tocytological atypia. Despite a mostly favorable prognosisof EH, risk of progression to atypia is nearly 2% per year.The next problem is absence of clear criteria on which casewill have an unfavorable prognosis and EH will progress toAH and endometrial cancer. Markers of response of EH andAH to the first line therapy such as progestin are not wellinvestigated either. Investigation of ER and PGR expressionin normal (NE) and hyperplastic endometrium can be usefulfor future development of treatment algorithms in differentendometrial hyperplasia morphotypes and forecastingresponses to progestin therapy.Objective: To investigate the expression of estradiol andprogesterone receptors in the glandular and stromal cells ofnormal endometrium and in the different morphotypes ofendometrial hyperplasia.Material and Methods: Endometrial samples taken from137 women were investigated: 40 – with normal proliferativeand secretory endometrium (NE), 61 – endometrialhyperplasia without atypia (ЕH), 36 – endometrialhyperplasia with atypia (AH). Routine histopathologicaland immunohistochemical (IHC) examination of nuclearantigens in the endometrium samples was conducted. Then,IHC examination was carried out on the paraffin blocksusing monoclonal and polyclonal antibodies and systems ofvisualization. Expression of estradiol (ER) and progesterone(PGR) receptors was investigated. Taking into account thatcells with positive reaction to ER and PGR have significantdifferences in the intensity of IHC coloring, we used theaverage value or H-index according to the number of cellswith positive reaction and reaction intensity. Values from0 to 50 on the H-index were considered for the absence ofER and PGR expression, from 50 to 100 - expression ofantigens to receptors was considered as weakly positive;100 points or more - as positive. Statistical processing ofresults was done using licensed program Statistics (V 6.1;Statsoft, USA).Results: ER expression of EH both in glandular cells (180±8.3) and stromal cells (170.5±4.1) was close to resultsof proliferative NE (193.1±12.2 in the glandular and 166±9.7in the stromal cells), but 1,43 times exceeded indicators inthe glandular (180±8.3 vs 125.4±5.7; p<0.05) and 1.9 timesin the stromal cells (170.±4. vs 122.±4.; p<0.5) of secretoryNE. PGR expression in the glandular cells of EH wasalmost the same as this indicator of NE. PGR expressionin the stromal cells of EH was 197.±9.3 points and it wassignificantly higher compared to NE. On the contrary, withAHE ER and PGR expression significantly and reliablydecreased. ER expression of glandular cells (74.6±3.9points) was 2.6 times lower compared to proliferative NE(p<0.05) and 2.4 times lower to EH (р<0.05). ER of stromalAHE cells dropped to 30.3±2.8, which was 5.5 times lowerthan in NE of the proliferative phase (p<0.002) and 5.6times lower than in EH (p<0.002). PGR expression had thesame direction and also decreased. AHE glandular PGRexpression (71.1±2.3) was 2.7-2.5 times lower than thisindicator in the proliferative and secretory NE respectively(p<0.05). Reliable differences in PGR expression betweenAHE and EH were found. Glandular PGR expression indexAHE was 2.8 times lower than the same EH indicator(p<0.05), stromal one was 2.4 times lower (p<0.05).Conclusion: Estradiol and progesterone receptors dataof endometrium will be useful for future developmentof carcinogenesis risk stratification at the early stage,identifying patients with high risk of endometrial cancerand also for choosing the optimal way to influence thepathological process in the endometrium.