Volume 5, Issue 1, January 2020, Page: 18-27
Diagnostic Value of Serum Biomarker Human Epididymis Protein4 in Ovarian Cancers
Rimaz Elhag Gurashi, Clinical Chemistry Department, Faculty of Medical Laboratory Sciences, Al-neelain University, Khartoum, Sudan
Moawia Elsadig Hummeida, Department of Obgyn, Faculty of Medicine, Al-neelain University, Khartoum, Sudan
Faisal Galal Abdelaziz, Gynological Oncologist, Military Hospital, Omdurman, Sudan
Received: Oct. 6, 2019;       Accepted: Dec. 27, 2019;       Published: Jan. 17, 2020
DOI: 10.11648/j.ajlm.20200501.13      View  317      Downloads  141
Ovarian cancer is the fifth most common cancer affecting women today. In fact, ovarian cancer is responsible for more deaths than any other type of female reproductive cancer. According to the American Cancer Society, 20,000 women are diagnosed with ovarian cancer each year. Since diagnosis early on is associated with improved rates of survival, an effective screening strategy that detects early stage ovarian cancer may have a significant impact on mortality from the disease. Cancer researchers are under way to develop more accurate tumor markers that can be used to identify disease in its early stages, to predict the effectiveness of treatment, or to predict the chance of cancer recurrence after treatment has ended. Cancer antigen 125 (CA125) is an established biomarker for ovarian cancer detection. As CA125 effectiveness in the identification of the malignancy is threatened by its low diagnostic specificity, measurements of other tumor marker, Human epididymis protein4 (He4), in the serum have been proposed for improving the sensitivity and specificity of laboratory identification of the disease. The aim of our research study was to evaluate the diagnostic performance of Human epididymis protein4 (He4) in ovarian cancer patients. Our study group consisted of 90 Sudanese ladies age range (16-80) years old attending Gynological Oncology clinics in Omdurman Military hospitals. Blood samples were collected and centrifugated using standardized procedure, all analyses were performed in serum samples. Human epididymis protein 4 (HE4) serum concentration were determined using Enzyme-Linked Immunosorbent Assay (CUSABIO ELISA kits) for the quantitative invitro diagnostic measurement. the data were treated Statistically. The study results shown that epithelial ovarian cancer is the most common ovarian cancer type in Sudan followed by germ cell tumors. Serum level of Human epididymis protein 4 (HE4) biomarker within the reference range in the control group. In contrast, increasing serum level of Human epididymis protein 4 (HE4) were obtained in the ovarian cancer patients, A general agreement that a combination of multiple biomarkers may increase diagnostic sensitivity and specificity over use of individual marker. The results of this study confirmed that, by combining He4 measurements with cancer antigen 125, we can improve the diagnostics performance for OC. HE4 is a relatively stable serum biomarker for ovarian cancer with a higher diagnostic prediction.
Ovarian Cancer, Biomarker, HE4, Epithelial OV
To cite this article
Rimaz Elhag Gurashi, Moawia Elsadig Hummeida, Faisal Galal Abdelaziz, Diagnostic Value of Serum Biomarker Human Epididymis Protein4 in Ovarian Cancers, American Journal of Laboratory Medicine. Vol. 5, No. 1, 2020, pp. 18-27. doi: 10.11648/j.ajlm.20200501.13
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
National Comprehensive Cancer Network (NCCN). Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Available from: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. 2016. USA.
Schwartz PE. Current diagnosis and treatment modalities for ovarian cancer. Cancer Treat Res 2002; 107: 99-118.
Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumors of female reproductive organs. 4th ed. Lyon: International Agency for Research on Cancer; 2014.
Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch 2012; 460: 237-49.
Jaime Prat. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynecol Obstet 2014; 124 (1): 1-5. JGynecol Oncol Vol. 26, No. 2: 87-89 http://dx.doi.org /10.3802 /jgo.2015.26.2.87
Shahrazad Ehdaivand, etal. 2016, WHO classification of Ovarian Neoplasms, Pathology Outlines.com, Inc.
Yao Chen, Suihai Wang, Tiancai Liu, Yingsong Wu, Ji-Liang Li, and Ming Li, 2016. WAP four-disulfide core domain protein 2 gene (WFDC2) is a target of estrogen in ovarian cancer cells. Journal of Ovarian Research 2016; 9: 10.
American Joint Committee on Cancer. Ovary and Primary Peritoneal Carcinoma. In: AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010: 419-428.
American Cancer Society. Cancer Facts and Figures 2016. Atlanta, GA: American Cancer Society; 2016.
Melinda M. Protani, Christina M. Nagle, and Penelope M. Webb. Obesity and Ovarian Cancer Survival: A Systematic Review and Meta-analysis, www.aacrjournals.org, 2012; DOI: 10.1158/1940-6207.CAPR-12-0048.
Valerie McGuire, Patricia Hartge, Linda M. Liao, Rashmi Sinha, Leslie Bernstein, Alison J. Canchola, Garnet L. Anderson, Marcia L. Stefanick, Alice S. Whittemore. Parity and Oral Contraceptive Use in Relation to Ovarian Cancer Risk in Older Women. 2016; DOI: 10.1158/1055-9965.EPI-16-0011.
Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and metaanalysis. Acta Paediatr. 2015; 104 (467): 96-113.
Alison Volpe Holmes, Heather G. Jones, Brock C. Christensen, Breastfeeding and Cancer Prevention, April, 2017. NH Comprehensive Cancer Collaboration in partnership with Dartmouth-Hitchcock Norris Cotton Cancer Center and its NCI National Outreach Network Community Health Educator Site.
Muhammad Zahid, Cheryl L. Beseler, James B. Hall, Tricia LeVan, Ercole L. Cavalieri and Eleanor G. Rogan. Unbalanced estrogen metabolism in ovarian cancer, International Journal of Cancer. 25 January 2014. DOI: 10.1002/ijc.28565.
Sami Azrak. Hereditary Ovarian Cancer and Germline Mutations: Review Article. Journal of Genetics and Genetic Engineering Volume 1, Issue 1, 2017, PP 31-42.
American collage of Obstetrician and Gynecologist, fact sheet in BRCA1 and BRCA2 mutations. Oct 2017.
Francis S. Collins. Study reveals genomic similarities between breast cancer and ovarian cancers. National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of NIH. Sept. 23, 2012.
Jacobs IJ, Menon U. Progress and challenges in screening for early detection of ovarian cancer. MolCell Proteomics 2004; 3: 355^66.
Hristina Fotopoulou, Marcia Hall, Derek Cruickshank, Hani Gabra, Raji Ganesan, Cathy Hughes, Sean Kehoe, Jonathan Ledermann, Jo Morrison, Raj Naik, Phil Rolland, Sudha Sundar. British Gynaecological Cancer Society (BGCS) Epithelial Ovarian /Fallopian Tube / Primary Peritoneal Cancer. 2014; 1-48. Guidelines: https://www.rcog.org.uk/en/guidelines-researchservices/guidelines/clinical-governance-advice-1a/.
American cancer society, cancer facts and figures 2017. special section: Rare cancers in adults. Atlanta 2017. https://www. American cancer society.com.
National Comprehensive Cancer Network. NCCN Guidelines Version 4. Hereditary Breast and/or Ovarian Cancer Syndrome. 2013. USA.
Network SIG. Management of epithelial ovarian cancer. SIGN Publication No 135. Edinburg: SIGN; 2013.
Health Resources & Services Administration. Women’s preventive services guidelines. https://www.hrsa.gov/womensguidelines2016/index.html. Accessed January 17, 2017.
American Family Physician. screening for Gynecologic Conditions with Pelvic Examination: Recommendation Statement, August 15, 2017. Volume 96, Number 4 www.aafp.org/afp.
Jyothi Kancherla, Raghu Kalahasti, K P A Chandra Sekhar, Srikanth Babu Yarlagadda, S Parimala Devi 2017. Histomorphological Study of Ovarian Tumors: An Institutional Experience of 2 Years. International Journal of Scientific Study | June 2017 | Vol 5 | Issue 3.
Vathany Kulasingam and Eleftherios P Diamandis. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies nature clinical practice oncology oct 2008, vol 5, no 10.
Chhikara, N., M. Saraswat, A. K. Tomar, S. Dey, S. Singh, and S. Yadav. Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor." PLoS One 2012; 7 (11): e47672.
Hellstrom, I., P. J. Heagerty, E. M. Swisher, P. Liu, J. Jaffar, K. Agnew, and K. E. Hellstrom."Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms. Cancer Lett. 2010 Oct 1; 296 (1): 43-8. Cancer.
Georgakopoulos, P., S. Mehmood, A. Akalin, and K. R. Shroyer. Immunohistochemical localization of HE4 in benign, borderline, and malignant lesions of the ovary." Int J Gynecol Pathol 2012; 31 (6): 517-23.
Tokuishi, K., S. Yamashita, K. Ohbo, and K. Kawahara. Splice variant HE4- V3 expression is associated with favorable prognosis in pulmonary adenocarcinoma. Tumour. 2012 Feb; 33 (1): 103-9.
Liao, J. B., Y. Y. Yip, E. M. Swisher, K. Agnew, K. E. Hellstrom, and I. Hellstrom. Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms: Clinical correlates." Gynecol Oncol 2015; 137 (3): 430-5.
Moore, R. G., M. C. Miller, E. E. Eklund, K. H. Lu, R. C. Bast, and G. Lambert-Messerlian. Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age." Am J Obstet Gynecol 2012; 206 (4): 349. e1-7.
Park, Y., Y. Kim, E. Y. Lee, J. H. Lee, and H. S. Kim. Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer." Int J Cancer 2012; 130 (5): 1136-44.
Terry, K. L., H. Schock, R. T. Fortner, etal 2016. "A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort." Clin Cancer Res. 22 (18): 4664-75.
Park, Y., J. H. Lee, D. J. Hong, E. Y. Lee, and H. S. Kim. Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non gynecologic diseases." Clin Biochem 2011; 44 (10-11): 884-8.
Marianne Hallamaa. Overian cancer marker HE4 in hormone-related gynecological conditions and diagnosis of overian granulosa cell tumors turn ylopiston julkaisuja- Annales universitis Turkuensissarj. - ser. D osa - tom. 1278 | Medica – Odontologica 2017 | Turku 201.
US Preventive Services Task Force. Screening for Ovarian cancer. Accessed November 10, 2014 http://www.uspreventiveservicestaskforce.org/uspstf/uspsovar.htm.
Skates S. OcS: development of the risk of ovarian cancer algorithm (ROCA) and ROCA screening trials. Int J Gynecol Cancer. 2012; 22 (suppl 1): S24-S26.
American college of Obstetricians and Gynecologists. Practice bulletin no. 83: management of Adnexal masses. Washington, dc: American college of Obstetricians and Gynecologists; 2007.
Høgdall, Estrid, Nedergaard, Karlsen. Diagnostic value of HE4, CA125 and the roma index in ovarian cancer. 2011, Denmark.
Drescher, Urban N, Hartge. Potential role of HE4 in multimodal screening for epithelial ovarian cancer 2011, USA.
Rimaz A. Gurashi, Moawia E. Hummeida, F. G. Abdelaziz. Diagnostic Value of Serum Cancer Antigen125 in Ovarian Cancer Patients. International Journal of Development Research Vol. 08, Issue, 01, pp. 18644-18650, January, 2018.
Browse journals by subject