Farname Inc. in collaboration with Iranian Society of Gynecology Oncology

Authors

1 Assistant Professor Dr. Fereshteh Ameli, Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Iran

2 Postgraduate Doctorate Degree in Pathology(Pathologist), Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

3 Professor of Pathology, Consultant Anatomical Pathologist, Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

Abstract

Introduction:
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.

Keywords

  1. References 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. 2. Ajani MA, Salami A, Awolude OA, Oluwasola AO. Hormone–receptor expression status of epithelial ovarian cancer in Ibadan, South-western Nigeria. The Pan African Medical Journal. 2017;27. 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. Scientific reports. 2017;7(1):1-7. 4. Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Molecular biology international. 2014;2014. 5. English DP, Roque DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Molecular diagnosis & therapy. 2013;17(2):85-99. 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. 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. Archives of pathology & laboratory medicine. 2018;142(11):1364-82. 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. 11. Pokhriyal R, Hariprasad R, Kumar L, Hariprasad G. Chemotherapy resistance in advanced ovarian cancer patients. Biomarkers in cancer. 2019;11:1179299X19860815. 12. Nimmagadda S, Penet M-F. Ovarian cancer targeted theranostics. Frontiers in oncology. 2020;9:1537. 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. European journal of cancer. 2006;42(2):149-58. 15. Ory H. Functional ovarian cysts and oral contraceptives: negative association confirmed surgically. Journal of the American Medical Association. 1974;228(1):68-9. 16. Cannistra SA. Cancer of the ovary. New England Journal of Medicine. 2004;351(24):2519-29. 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. International Journal of Gynecologic Pathology. 2004;23(1):41-4. 18. Ho C. Pattern of ovarian tumours among Malaysian women at General Hospital~ Kuala Lumpur. Med J Malaysia. 1992;47(2). 19. Lindgren PR, Cajander S, Bäckström T, Gustafsson J-Å, Mäkelä S, Olofsson JI. Estrogen and progesterone receptors in ovarian epithelial tumors. Molecular and cellular endocrinology. 2004;221(1-2):97-104. 20. Abu-Jawdeh G, Jacobs T, Niloff J, Cannistra S. Estrogen receptor expression is a common feature of ovarian borderline tumors. Gynecologic oncology. 1996;60(2):301-7. 21. Agarwal N, Rao D, Murgeshan K, Verma U, Mittal S, Buckshee K, et al. Clinical evaluation of steroid receptors in ovarian neoplasms. International Journal of Gynecology & Obstetrics. 1987;25(2):145-9. 22. Fujimura M, Hidaka T, Kataoka K, Yamakawa Y, Akada S, Teranishi A, et al. Absence of Estrogen Receptor-[alpha] Expression in Human Ovarian Clear Cell Adenocarcinoma Compared With Ovarian Serous, Endometrioid, and Mucinous Adenocarcinoma. The American journal of surgical pathology. 2001;25(5):667-72. 23. Rutherford T, Brown WD, Sapi E, Aschkenazi S, Muñoz A, Mor G. Absence of estrogen receptor-[beta] expression in metastatic ovarian cancer. Obstetrics & Gynecology. 2000;96(3):417-21. 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, et al. The pattern of estradiol and progesterone differs in serum and tissue of benign and malignant ovarian tumors. International journal of oncology. 2002;21(3):583-9. 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 journal of pathology and microbiology. 2012;55(1):33. 27. McCaughan H, Um I, Langdon SP, Harrison DJ, Faratian D. HER2 expression in ovarian carcinoma: caution and complexity in biomarker analysis. Journal of clinical pathology. 2012;65(7):670-1. 28. 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 Journal of Cancer. 2018;9(4):300-9. 29. New Treatment of Advanced Ovarian Cancer: A Literature Review. J Obstet Gynecol Cancer Res. 2019; 4 (4):131-134, URL: http://jogcr.com/article-1-237-en.html