Iranian Society of Gynecology Oncology

Document Type : Original Research Article


1 Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran

2 Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia


The highest mortality rate in gynecologic cancers is attributed to ovarian origin. Expression of the estrogen and progesterone receptors (ER and PR); and Human epidermal growth factor receptor 2 (Her2/neu) in endometrial cancer and breast cancer were found to be associated with the response to treatment and prognosis. However, because of inconsistent results from previous studies, the data regarding ovarian cancer are still inconclusive.
Materials and methods: Current retrospective cross-sectional study was performed on 234 tissue samples of different types of ovarian tumors (benign, borderline and malignant) from the archive of the University Kebangsaan Malaysia Medical Center during 10 years. Tissue microarrays were constructed on representative areas from formalin fixed paraffin embedded tissue blocks using ER, PR and HER2 immunohistochemical staining. Results: Prevalence of ER and PR overexpression was 36% and 35% in benign, 8% and 24% in borderline tumors with 51% and 46% in malignant tumors, respectively. ERα overexpression was more common among serous malignant ovarian tumors (49%) (p<0.001). PR positivity was more prevalent in serous benign tumors (p=0.02).There was no significant relationship between stage and the status of ERα (p=0.12) and PR (p=0.19). Her2/neu overexpression was only seen in borderline neoplasms (8%) and malignant mucinous tumors (4%). No association was found between Her2/neu overexpression and the level of tumor differentiation, tumor stage, size, and patient’s age.
Conclusion: The observed ERα positivity in serous carcinoma and Her2/neu overexpression in malignant mucinous tumor, could be considered as a clue for choosing therapeutic agents. The role of anti-HER2 therapy in clear cell carcinoma is still debated and needs more investigations.


Main Subjects

1. Shen F, Zhang X, Zhang Y, Ding J, Chen Q. Hormone receptors expression in ovarian cancer taking into account menopausal status: a retrospective study in Chinese population. Oncotarget. 2017;8(48):84019. [DOI:10.18632/oncotarget.20251] [PMID] [PMCID]
2. Ajani MA, Salami A, Awolude OA, Oluwasola AO. Hormone-receptor expression status of epithelial ovarian cancer in Ibadan, South-western Nigeria. Pan Afr Med J. 2017;27:259. [DOI:10.11604/pamj.2017.27.259.11883] [PMID] [PMCID]
3. Chen S, Dai X, Gao Y, Shen F, Ding J, Chen Q. The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer. Sci Rep. 2017;7(1):1-7. [DOI:10.1038/s41598-017-17265-6] [PMID] [PMCID]
4. Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Mol Biol Int. 2014;2014:852748. [DOI:10.1155/2014/852748] [PMID] [PMCID]
5. English DP, Roque DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Mol Diagn Ther. 2013;17(2):85-99. [DOI:10.1007/s40291-013-0024-9] [PMID] [PMCID]
6. Luo H, Xu X, Ye M, Sheng B, Zhu X. The prognostic value of HER2 in ovarian cancer: a meta-analysis of observational studies. PloS One. 2018;13(1):e0191972. [DOI:10.1371/journal.pone.0191972] [PMID] [PMCID]
7. Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JM, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. Arch Pathol Lab Med. 2018;142(11):1364-82. [DOI:10.5858/arpa.2018-0902-SA] [PMID]
8. Herrington CS. WHO Classification of Tumours Female Genital Tumours: International Agency for Research on Cancer; 2020.
9. Elmahdi NM, Latiff LA, Zavare M, Ismail M, Manaf RA, Bin Abu Bakar A. A cross-sectional study of ovarian cancer knowledge and its determinants among female employees in a public University Malaysia. Mal J Med Health Sci. 2017;13:71-9.
10. Seidman JD, Cho KR, Ronnett BM, Kurman RJ. Surface epithelial tumors of the ovary. Blaustein's pathology of the female genital tract: Springer; 2011. p. 679-784. [DOI:10.1007/978-1-4419-0489-8_14]
11. Pokhriyal R, Hariprasad R, Kumar L, Hariprasad G. Chemotherapy resistance in advanced ovarian cancer patients. Biomark Cancer. 2019;11:1179299X19860815. [DOI:10.1177/1179299X19860815] [PMID] [PMCID]
12. Nimmagadda S, Penet M-F. Ovarian cancer targeted theranostics. Front Oncol. 2020;9:1537. [DOI:10.3389/fonc.2019.01537] [PMID] [PMCID]
13. Nucci MR, Parra-Herran C. Gynecologic Pathology E-Book: A Volume in the Series: Foundations in Diagnostic Pathology: Elsevier Health Sciences; 2019.
14. Morice P. Borderline tumours of the ovary and fertility. Eur J Cancer. 2006;42(2):149-58. [DOI:10.1016/j.ejca.2005.07.029] [PMID]
15. Ory H. Functional ovarian cysts and oral contraceptives: negative association confirmed surgically. JAMA. 1974;228(1):68-9. [DOI:10.1001/jama.1974.03230260042022]
16. Cannistra SA. Cancer of the ovary. New Eng J Med. 2004;351(24):2519-29. [DOI:10.1056/NEJMra041842] [PMID]
17. Seidman JD, Horkayne-Szakaly I, Haiba M, Boice CR, Kurman RJ, Ronnett BM. The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol. 2004;23(1):41-4. [DOI:10.1097/01.pgp.0000101080.35393.16] [PMID]
18. Ho C. Pattern of ovarian tumours among Malaysian women at General Hospital~ Kuala Lumpur. Med J Malaysia. 1992;47(2):139-46.
19. Lindgren PR, Cajander S, Bäckström T, Gustafsson J-Å, Mäkelä S, Olofsson JI. Estrogen and progesterone receptors in ovarian epithelial tumors. Mol Cell Endocrinol. 2004;221(1-2):97-104. [DOI:10.1016/j.mce.2004.02.020] [PMID]
20. Abu-Jawdeh G, Jacobs T, Niloff J, Cannistra S. Estrogen receptor expression is a common feature of ovarian borderline tumors. Gynecol Oncol. 1996;60(2):301-7. [DOI:10.1006/gyno.1996.0043] [PMID]
21. Agarwal N, Rao D, Murgeshan K, Verma U, Mittal S, Buckshee K, Chapeker T. Clinical evaluation of steroid receptors in ovarian neoplasms. Int J Gynaecol Obstet. 1987;25(2):145-9. [DOI:10.1016/0020-7292(87)90009-9] [PMID]
22. Fujimura M, Hidaka T, Kataoka K, Yamakawa Y, Akada S, Teranishi A, Saito S. Absence of Estrogen Receptor-[alpha] Expression in Human Ovarian Clear Cell Adenocarcinoma Compared With Ovarian Serous, Endometrioid, and Mucinous Adenocarcinoma. Am J Surg Pathol. 2001;25(5):667-72. [DOI:10.1097/00000478-200105000-00016] [PMID]
23. Rutherford T, Brown WD, Sapi E, Aschkenazi S, Muñoz A, Mor G. Absence of estrogen receptor-[beta] expression in metastatic ovarian cancer. Obstet Gynecol. 2000;96(3):417-21. [DOI:10.1016/S0029-7844(00)00917-0] [PMID]
24. Seidman JD, Cho KR, Ronnett BM, Kurman RJ. Surface epithelial tumors of the ovary. Blaustein's pathology of the female genital tract2002.
25. Lindgren PR, Backstrom T, Cajander S, Damber M-G, Mahlck C-G, Zhu D, Olofsson J. The pattern of estradiol and progesterone differs in serum and tissue of benign and malignant ovarian tumors. Int J Oncol. 2002;21(3):583-9. [DOI:10.3892/ijo.21.3.583] [PMID]
26. Sylvia MT, Kumar S, Dasari P. The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumors and its correlation with clinicopathologic variables. Indian J Pathol Microbiol. 2012;55(1):33-7. [DOI:10.4103/0377-4929.94852] [PMID]
27. Ayadi L, Chaabouni S, Khabir A, Amouri H, Makni S, Guermazi M, et al. Correlation Between Immunohistochemical Biomarkers Expression and Prognosis of Ovarian Carcinomas in Tunisian Patients. World J Oncol. 2010;1(3):118-28. [DOI:10.4021/wjon2010.06.213w] [PMID] [PMCID]
28. Arias-Pulido H, Smith HO, Joste NE, Bocklage T, Qualls CR, Chavez A, et al. Estrogen and progesterone receptor status and outcome in epithelial ovarian cancers and low malignant potential tumors. Gynecol Oncol. 2009;114(3):480-5. [DOI:10.1016/j.ygyno.2009.05.045] [PMID] [PMCID]
29. McCaughan H, Um I, Langdon SP, Harrison DJ, Faratian D. HER2 expression in ovarian carcinoma: caution and complexity in biomarker analysis. J Clin Pathol. 2012;65(7):670-1. [DOI:10.1136/jclinpath-2011-200616] [PMID]
30. Asadinejad E, Abdirad A, Nili F, Soleimani V. HER2 Overexpression in Borderline and Malignant Ovarian Tumors: A Cross-sectional Study in an Iranian Population and Literature Review. Middle East J Cancer. 2018;9(4):300-9.