Diagnostic utility of immunohistochemical expression of HE4 in Epithelial Ovarian Neoplasm
Keywords:
Biomarker, Epithelial ovarian neoplasm, HE4
Abstract
Background: Mortality in case of ovarian malignancy is high due to late diagnosis. Early and accurate diagnosis can improve the case specific management. HE4 (human epididymis protein 4) which is proved to be overexpressed in the ovarian cancer cells, is considered a new biomarker for ovarian cancer diagnosis. Aims and objectives: The study was undertaken to evaluate the immunohistochemical expression of HE4 in various epithelial ovarian neoplasm. Material and Methods: It was a cross sectional, prospective, single institution based study, conducted in the department of Pathology in collaboration with the department of Gynecology and Obstetrics, from December 2016 to January 2019 in our institution. A total 71 cases were selected for this study. Results: Serous tumour was the most common epithelial tumour followed by mucinous tumour. Highest percentage of expression of HE4 was seen in high grade serous cancer and malignant endometrioid tumour. Benign serous and mucinous tumour shows negative expression mostly. We found statistically significant correlation between HE4 expression and different types of epithelial ovarian tumours (p=0.000). Conclusions: HE4 was highly expressed in malignant ovarian tumour especially serous and endometrioid carcinoma and can be used as an important biomarker for malignant ovarian neoplasm. Expression in high grade ovarian serous cancer supports its prognostic value also.References
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7. Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpresse by serous and endometrioid ovarian carcinomas. Cancer Res
2005;65:2162–9.
8. Anastasi E, Marchei GG, Viggiani V, et al. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol 2010;31:113–9.
9. Bulut.T, Celik. B, A.D. Yalcin, S. Keser. Tissue expression of HE4 and its correlation with CA125 and p53 in high grade serous ovarian carcinoma. European journal of Gynaecological Oncology. January 2018.
10.Schummer M, NgWV, Bumgarner RE,Nelson PS, Schummer B, BednarskiDW et al Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 1999; 238: 375–385.
11. Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res 2003; 63: 3695– 3700.
12. Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with pelvic mass.Gynec Oncol.2009;(112):40-6.
13. Escudero JM, Auge JM, Filella X, Torne A, Pahisa J, Molina R.The utility of serum human epididymis protein 4 (HE4) in patients with malignant and non malignant diseases: comparison with CA125. Clin Chem. 2011 (in press)
14. Agarwal P, Kulkarni DG, Chakrabarti PR, Chaurasia S, Dixit M, Gupta K. Clinicopathological Spectrum of Ovarian Tumors: A 5-Year Experience in a Tertiary Health Care Center. Journal of Basic and Clinical Reproductive Sciences, 2015;4(2).
15. Malik I.A. A Prospective Study of Clinico-pathological Features of Epithelial Ovarian Cancer in Pakistan. JPMA 2002;52:155.
16. Maheshwari V, Tyagi SP, Saxena K, Tyagi N, Sharma R, Aziz M, Hameed F. Surface epithelial tumours of the ovary. Indian J Pathol Microbiol. 1994;37(1):75-85.
17. Siddiqui RB, Shankar B, Khan IM. Morphological Patterns of Ovarian Neoplasms in Different Age Groups - A Center based study. P J M H S 2015;9(4): 1139.
18. Li-e Zheng, Jun – ying Qu, Fei He. The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer. Open Med 2016; 11: 125- 132.
19.Rahmat F, Ithnin H Immunohistochemical Expression of Human Epididymis 4 (He4) in Ovarian Serous Carcinoma in Hospital Serdang from the Year 2006- 2013. Gynecol Obstet (Sunnyvale) 2017; 7: 453. doi: 10.4172/2161-0932.1000453 l
20.Penelope Georgakopoulos, Saira Mehmood, Ali Akalin Kenne tShroyer Immunohistochemical Localization of HE4 in Benign, Borderline, and Malignant Lesions of the Ovary.International Journal of Gynecological Pathology 31:517–523.
21. Bulut.T, Celik.B, A.D.Yalcin, S. Keser. Tissue expression of HE4 and its correlation with CA125 and p53 in high grade serous ovarian carcinoma.European journal of GynaecologicalOncology. 2017 ISSN: 0392-2936 XXXVIII, n. 5, 2017 doi: 10.12892/ejgo3992.2017
2. WHO Classification of Tumours of Female Reproductive Organs, In: Robert J Kurman, Maria Lusia Carcangiu, C.Simon Herrington, Robert H. Young ed.4th,France, IARC, Lyon: IARC,2014 p 12-13.
3. Nolen B, Marrangoni A, Velikokhatnaya L, Prosser D, Winans M, Gorelik E, Anna LA: A serum based analysis of ovarian epithelial tumorigenesis. Gynecol Oncol 2009, 112(1): 47-54.
4. Pettersson F. Annual Report on the Results of Treatment in Gynecological Cancer, FIGO. Int J Gynaecol Obstet 1994;22:83–102.
5. Ozols RF. Update on the management of ovarian cancer. Cancer J 2002;8:( 1): 22–30.
6. Galgano MT, Hampton GM, Frierson HF, Jr. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol 2006;19:847–53.
7. Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpresse by serous and endometrioid ovarian carcinomas. Cancer Res
2005;65:2162–9.
8. Anastasi E, Marchei GG, Viggiani V, et al. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol 2010;31:113–9.
9. Bulut.T, Celik. B, A.D. Yalcin, S. Keser. Tissue expression of HE4 and its correlation with CA125 and p53 in high grade serous ovarian carcinoma. European journal of Gynaecological Oncology. January 2018.
10.Schummer M, NgWV, Bumgarner RE,Nelson PS, Schummer B, BednarskiDW et al Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 1999; 238: 375–385.
11. Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res 2003; 63: 3695– 3700.
12. Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with pelvic mass.Gynec Oncol.2009;(112):40-6.
13. Escudero JM, Auge JM, Filella X, Torne A, Pahisa J, Molina R.The utility of serum human epididymis protein 4 (HE4) in patients with malignant and non malignant diseases: comparison with CA125. Clin Chem. 2011 (in press)
14. Agarwal P, Kulkarni DG, Chakrabarti PR, Chaurasia S, Dixit M, Gupta K. Clinicopathological Spectrum of Ovarian Tumors: A 5-Year Experience in a Tertiary Health Care Center. Journal of Basic and Clinical Reproductive Sciences, 2015;4(2).
15. Malik I.A. A Prospective Study of Clinico-pathological Features of Epithelial Ovarian Cancer in Pakistan. JPMA 2002;52:155.
16. Maheshwari V, Tyagi SP, Saxena K, Tyagi N, Sharma R, Aziz M, Hameed F. Surface epithelial tumours of the ovary. Indian J Pathol Microbiol. 1994;37(1):75-85.
17. Siddiqui RB, Shankar B, Khan IM. Morphological Patterns of Ovarian Neoplasms in Different Age Groups - A Center based study. P J M H S 2015;9(4): 1139.
18. Li-e Zheng, Jun – ying Qu, Fei He. The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer. Open Med 2016; 11: 125- 132.
19.Rahmat F, Ithnin H Immunohistochemical Expression of Human Epididymis 4 (He4) in Ovarian Serous Carcinoma in Hospital Serdang from the Year 2006- 2013. Gynecol Obstet (Sunnyvale) 2017; 7: 453. doi: 10.4172/2161-0932.1000453 l
20.Penelope Georgakopoulos, Saira Mehmood, Ali Akalin Kenne tShroyer Immunohistochemical Localization of HE4 in Benign, Borderline, and Malignant Lesions of the Ovary.International Journal of Gynecological Pathology 31:517–523.
21. Bulut.T, Celik.B, A.D.Yalcin, S. Keser. Tissue expression of HE4 and its correlation with CA125 and p53 in high grade serous ovarian carcinoma.European journal of GynaecologicalOncology. 2017 ISSN: 0392-2936 XXXVIII, n. 5, 2017 doi: 10.12892/ejgo3992.2017
Published
2019-11-23
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