Abstract
Background
Endometrial carcinoma (EC) is the third common gynecologic cancer in India. It consists of two major histological types: the most common endometrioid or type I EC and non-endometrioid or type II EC. They are biologically distinct, and various markers have been proposed as prognostic biomarkers in EC besides clinical and pathological features.
Objectives
To study the immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2/neu) in EC and to correlate them with various clinicopathological parameters.
Methods
IHC study of ER, PR and HER2/neu was performed on 35 cases of histopathologically diagnosed EC in hysterectomy specimens for a period of 4 years from 2014 to 2017.
Results
Majority of the patients were aged 51–60 years, and the common comorbid conditions were type 2 diabetes mellitus, hypertension and obesity. Histologically, 31 (88.57%) cases were of type 1 EC and 4 (11.43%) were of type II EC; in type II EC, 2 (5.7%) cases were papillary serous carcinoma and the remaining two cases each were malignant mixed Mullerian tumor (MMMT) and dedifferentiated carcinoma (DC). ER expression was observed in 29 cases (82.9%) and was statistically significant with tumor stage, tumor grade, histological type and intraglandular necrosis. PR expression was seen in 22 (62.9%) cases and showed significant association with tumor grade, myometrial invasion and histological type. HER2/neu was expressed in one case.
Conclusion
Establishing the diagnosis of molecular subtype of EC with limited markers, namely ER/PR, HER2/neu expression similar to breast cancer, may be useful to determine the treatment and prognosis, especially in developing countries. Studies with larger sample sizes may elucidate their role, which was the limitation in this study.
Similar content being viewed by others
References
Zhang Y, Zhao D, Gong C, Zhang F, He J, Zhang W, et al. Prognostic role of hormone receptors in endometrial cancer: a systematic review and meta analysis. World J Surg Oncol. 2015;13:208–19. https://doi.org/10.1186/s12957-015-0619-1.
Srijaipracharoen S, Tangjitgamol S, Tanvanich S, Manusirivithaya S, Khunnarong J, Thavaramara T, et al. Expression of ER, PR, and Her-2/neu in endometrial cancer: aclinicopathological study. Asian Pac J Cancer Prev. 2010;11(1):215–20.
Maheshwari A, Kumar N, Mahantshetty U. Gynecological cancers: a summary of published Indian data. South Asian J Cancer. 2016;5(3):112–20.
Konecny GE, Santos L, Winterhoff B, Hatmal M, Keeney GL, Mariani A, et al. A HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer. 2009;100(1):89–95.
Wilczyński M, Danielska J, Wilczyński J. An update of the classical Bokhman’s dualistic model of endometrial cancer. PrzMenopauzalny. 2016;15(2):63–8.
Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrialcancer. Lancet. 2016;387(10023):1094–108.
Baker J, Obermair A, Gebski V, Janda M. Efficacy of oral or intrauterine device- delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature. Gynecol Oncol. 2012;125(1):263–70.
Longacre TA, Broaddus R, Chuang LT, Cohen MB, Jarboe EA, Mutter GL, et al. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the endometrium. Arch Pathol Lab Med. 2017;141(11):1508–12.
Woo JS, Apple SK, Sullivan PS, Rao JY, Ostrzega N, Moatamed NA. Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience. Diagn Pathol. 2016;11(1):102.
Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer. 2007;17(5):964–78.
Fisher B, Redmond C, Fisher ER, Caplan R. Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from national surgical adjuvant breast and bowel project protocol B-06. J Clin Oncol. 1988;6(7):1076–87.
Kalogiannidis I, Petousis S, Bobos M, Margioula-Siarkou C, Topalidou M, Papanikolaou A, et al. HER-2/neu is an independent prognostic factor in type I endometrial adenocarcinoma. Arch Gynecol Obstet. 2014;290(6):1231–7.
Binder PS, Mutch DG. Update on prognostic markers for endometrial cancer. Womens Health. 2014;10(3):277–88.
Gehrig PA, Van Le L, Olatidoye B, Geradts J. Estrogen receptor status, determined by immunohistochemistry, as a predictor of the recurrence of stage I endometrial carcinoma. Cancer. 1999;86(10):2083–9.
Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, et al. A Phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a gynecologic oncology group study. Gynecol Oncol. 2004;92(3):744–51.
Ellenson LH, Pirog EC. The female genital tract. In: Kumar V, Abbas AK, Aster JC (eds) Pathologic basis of disease, 9th edn. Philadelphia: Elsevier Saunders; pp 1014–18.
Merritt MA, Strickler HD, Einstein MH, Yang HP, Sherman ME, Wentzensen N, et al. Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors. Cancer Causes Control. 2016;27(6):737–48.
Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015;113(2):299–310.
Lapińska-Szumczyk S, Supernat A, Majewska H, Gulczyński J, Luczak A, Biernat W, et al. HER2-positive endometrial cancer subtype carries poor prognosis. Clin Transl Sci. 2014;7(6):482–8.
Tangen IL, Werner HM, Berg A, Halle MK, Kusonmano K, Trovik J, 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.
Konecny GE, Santos L, Winterhoff B, Hatmal M, Keeney GL, Mariani A, et al. HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer. 2009;100(1):89–95.
Ferrandina G, Ranelletti FO, Gallotta V, Martinelli E, Zannoni GF, Gessi M, et al. Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER),and progesterone (PR), p53, ki67, and neu protein in endometrial cancer. Gynecol Oncol. 2005;98(3):383–9.
Voss MA, Ganesan R, Ludeman L, McCarthy K, Gornall R, Schaller G, et al. Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation. Gynecol Oncol. 2012;124(1):15–20.
Al-Loh S, Al-Hussaini M. Undifferentiated endometrial carcinoma: a diagnosis frequently overlooked. Arch Pathol Lab Med. 2013;137(3):438–42.
Mylonas I. Prognostic significance and clinical importance of estrogen receptor alpha and beta in human endometrioid adenocarcinomas. Oncol Rep. 2010;24:385–93.
Huvila J, Talve L, Carpén O, Edqvist PH, Pontén F, Grénman S, 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.
Zannoni GF, Monterossi G, De Stefano I, Gargini A, Salerno MG, Farulla I, et al. The expression ratios of estrogen receptor α (ERα) to estrogen receptor β1(ERβ1) and ERα to ERβ2 identify poor clinical outcome in endometrioid endometrial cancer. Hum Pathol. 2013;44(6):1047–54.
Buza N, Roque MD, Santin AD. HER2/neu in endometrial cancer-a promising therapeutic target with diagnostic challenges. Arch Pathol Lab Med. 2014;138:343–50.
Gul AE, Keser SH, Barisik NO, Kandemir NO, Cakir C, Sensu S, et al. The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas. Diagn Pathol. 2010;5:13.
Obeidat BR, Matalka II, Mohtaseb AA, Al-Kaisi NS. Selected immunohistochemicalmarkers in curettage specimens and their correlation with finalpathologic findings in endometrial cancer patients. Pathol Oncol Res. 2013;19(2):229–35.
Suthipintawong C, Wejaranayang C, Vipupinyo C. Prognostic significance of ER, PR, Ki67, c-erbB-2, and p53 in endometrial carcinoma. J Med Assoc Thai. 2008;91(12):1779–84.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Mohapatra, K., Shivalingaiah, S.C. Immunohistochemical Expression of ER, PR and HER2/neu in Endometrial Carcinoma. Indian J Gynecol Oncolog 17, 54 (2019). https://doi.org/10.1007/s40944-019-0298-x
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s40944-019-0298-x