Histopathological study of endometrium in abnormal uterine bleeding with expression of oestrogen and progesterone receptors

New Indian Journal of OBGYN, May 2024

Background: Abnormal uterine bleeding (AUB) is a common gynaecological condition. Studies show that there is altered expression of oestrogen receptors (ER) and progesterone receptors (PR) in the endometrium which may have a role in the aetiology of abnormal bleeding. Objectives: To study the histopathological findings of endometrium and expression of oestrogen and progesterone receptors in the endometrium in patients with AUB. Materials and methods: A total of 63 endometrial biopsies were examined after obtaining ethical clearance from November 2018 to December 2019. After histopathological examination, all the cases were subjected to immunohistochemistry for ER and PR and were scored by Allred scoring system. Results: Majority of the patients were in the age group 41- 50 years and presented with heavy menstrual bleeding. Maximum number of cases were of endometrial hyperplasia (EH) without atypia (63%) followed by proliferative endometrium (21%), disordered proliferative endometrium (11%) and secretory endometrium (5%). Mean Allred score in AUB patients for ER expression in glands and stroma was significantly more than mean score for PR expression (glands – 7.3±1.5 vs 6.7 ± 1.8, p=0.00; stroma – 6.2±1.3 vs 5.8±1.6, p=0.00). ER expression in endometrial glands and stroma across various histologic patterns of AUB was higher than PR and this difference was significant in EH without atypia (7.2±1.8 vs 6.6±2, p=0.001; stroma – 6.2±1.16 vs 5.7±1.8, p=0.001). However, in other histological patterns, even though ER expression was higher than PR expression, test of significance could not be applied because of a smaller number of cases. Conclusion: Increased expression of ER was observed compared to PR in all histological patterns in patients with AUB. ER expression was significantly more in cases of endometrial hyperplasia without atypia indicating they may have a role in etiopathogenesis of endometrial hyperplasia.

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Histopathological study of endometrium in abnormal uterine bleeding with expression of oestrogen and progesterone receptors

ISSN Print – 2454-2334; ISSN Online – 2454-2342 DOI -10.21276/obgyn.2024.10.2.7 RESEARCH ARTICLE Histopathological study of endometrium in abnormal uterine bleeding with expression of oestrogen and progesterone receptors Priya Suneja, Prema Saldanha Corresponding author: Dr Priya Suneja, Ex Resident, MD Pathology, Department of Pathology, Yenepoya Medical College, Yenepoya University, Mangalore, India; Email : Distributed under Attribution-Non Commercial – Share Alike 4.0 International (CC BY-NC-SA 4.0) ABSTRACT Background: Abnormal uterine bleeding (AUB) is a common gynaecological condition. Studies show that there is altered expression of oestrogen receptors (ER) and progesterone receptors (PR) in the endometrium which may have a role in the aetiology of abnormal bleeding. Objectives: To study the histopathological findings of endometrium and expression of oestrogen and progesterone receptors in the endometrium in patients with AUB. Materials and methods: A total of 63 endometrial biopsies were examined after obtaining ethical clearance from November 2018 to December 2019. After histopathological examination, all the cases were subjected to immunohistochemistry for ER and PR and were scored by Allred scoring system. Results: Majority of the patients were in the age group 41- 50 years and presented with heavy menstrual bleeding. Maximum number of cases were of endometrial hyperplasia (EH) without atypia (63%) followed by proliferative endometrium (21%), disordered proliferative endometrium (11%) and secretory endometrium (5%). Mean Allred score in AUB patients for ER expression in glands and stroma was significantly more than mean score for PR expression (glands – 7.3±1.5 vs 6.7 ± 1.8, p=0.00; stroma – 6.2±1.3 vs 5.8±1.6, p=0.00). ER expression in endometrial glands and stroma across various histologic patterns of AUB was higher than PR and this difference was significant in EH without atypia (7.2±1.8 vs 6.6±2, p=0.001; stroma – 6.2±1.16 vs 5.7±1.8, p=0.001). However, in other histological patterns, even though ER expression was higher than PR expression, test of significance could not be applied because of a smaller number of cases. Conclusion: Increased expression of ER was observed compared to PR in all histological patterns in patients with AUB. ER expression was significantly more in cases of endometrial hyperplasia without atypia indicating they may have a role in etiopathogenesis of endometrial hyperplasia. Keywords: Abnormal uterine bleeding, endometrium, immunohistochemistry, oestrogen receptor, progesterone receptor, endometrial hyperplasia. Abnormal uterine bleeding (AUB) is a broad term that describes irregularities in the menstrual cycle involving frequency, regularity, duration, volume of flow and amount of blood loss1 and is a common cause of gynaecologic referral. It can occur at any age during reproductive period and is a common sign of different uterine disorders ranging from dysfunctional abnormalities (non-organic) to organic lesions such as polyps, hyperplasia with or without atypia, or carcinoma as well as hormonal and systemic diseases.2 The PALM–COEIN system (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified) aids in classification of women with AUB in a systematic manner which provides reliable information for accurate diagnosis and treatment.3 Immunohistochemistry (IHC) shows the presence of Received: 10th November 2021, Peer review completed: 7th April 2022, Accepted: 10th April 2023. Suneja P, Saldanha P. Histopathological study of endometrium in abnormal uterine bleeding with expression of oestrogen and progesterone receptors. The New Indian Journal of OBGYN. 2024; 10(2): 274 - 80. The New Indian Journal of OBGYN. 2024 (January (January-June);10(2) steroid receptors in human endometrium indicating that these mouse anti-human human PR Code PgR 636 from DAKO, and cells respond to steroid hormones oestrogen and universal secondary kit from DAKO which used DAKO progesterone. In cases of abnormal uterine bleeding, there is Real Envision as the detection system. Control specimen altered expression of these receptorss which may have a role chosen for ER PR was from a case of ductal carcinoma, c in aetiology. Using specific monoclonal antibodies, receptor breast which was ER and PR positive. IHC findings were expression can be estimated at the cellular level and thus, recorded and categorization was done according to standard their exact distribution, localization and intensity in protocol as given below. glandular and stromal cells can be studied.4 Scoring of IHC sections: Scoring was done by Allred Till date, AUB remains one of the enigmatic diseases. Its scoring system by calculating proportion score (PS) and the aetiology and pattern of expression of these hormonal intensity score (IS) as shown in table 1. receptors in the endometrium of AUB cases Table 1: Allred llred scoring system for estrogen and progesterone receptor evaluation 5, 6 is still not well understood. We undertook Proportion score (PS) Positive cells (%) Intensity Score (IS) Intensity of staining this study to understand the role of these Negative 0 >1% 0 None hormonal receptors in the etiopathogenesis 1 2 1-10% 1 Weak of AUB which could have important 3 11-33% 2 Intermediate 34-66 % 3 Strong implications in its management and further 4 5 >67 % implications in management. Total score = Sum of proportional score and Interpretation Intensity score (PS + IS) Materials and methods Negative This was an observational descriptive 0-2 2-8 Positive study of 63 patients with abnormal uterine bleeding. The studyy population included the patients Results diagnosed to have abnormal uterine bleeding who were Age range in our study was between 24 years to 50 years. admitted to Yenepoya Medical College and Hospital. The Mean age was 41.6 ± 5.9 years. Out of 63 cases, maximum study was started after obtaining permission from the number of cases belonged to the age range between 40 40-49 Institutional Ethics Committee (IEC). years. Heavy menstrual bleeding previously called as Sample size: Sixty three ree cases (Sample size calculated as menorrhagia was the most common symptom seen in 35 per SPSS version 23 with level of significance 5%, power (1 (1cases in our study followed by irregular bleeding in 20 cases, Beta) = 80%, effect size d= 0.18, with confidence interval of prolonged bleeding in 5 cases and dysmenorrhea in 3 cases 95%). depicted in figure 1. Sampling method: Convenience sampling. Inclusion criteria: The inclusion criteria of the study included patients with abnormal uterine bleeding ranging in the age group 18 to 50 years. Heavy menstrual bleeding Exclusion criteria:The The exclusion criteria of the study 5% included inadequate specimens, post-menopausal menopausal and 7% Irregular bleeding hysterectomy cases. The collection of cases was done from November 2018 to December 2019. (...truncated)


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Priya Suneja, Prema Saldanha. Histopathological study of endometrium in abnormal uterine bleeding with expression of oestrogen and progesterone receptors, New Indian Journal of OBGYN, 2024, pp. 274-280, Volume 2, DOI: 10.21276/obgyn.2024.10.2.7