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Original Research

Open Access

HE4: really a novel biomarker for ovarian cancer?

  • E. Yücel1
  • E. İlter1,*,
  • F.B. Aksungar2
  • A. Çelik1
  • B.H. Peker1
  • E. Şerifsoy3
  • S. Bozkurt1

1Maltepe University, Department of Obstetrics and Gynecology, Istanbul, Turkey

2Acıbadem University, Department of Biochemistry, Istanbul, Turkey

3Maltepe University, Department of Anesthesiology and Reanimation, Istanbul, Turkey

DOI: 10.12892/ejgo3312.2017 Vol.38,Issue 1,February 2017 pp.59-64

Published: 10 February 2017

*Corresponding Author(s): E. İlter E-mail: erdinilter@hotmail.com

Abstract

Ovarian cancer forms 4% of all cancers and approximately 23% of all gynecological cancers in women and is responsible for the 47% of deaths related to cancers of the genital tract of women. Tumor markers are the biochemical substances which can be detected in the presence of tumors. Generally they are either the products of tumoral tissues or secreted from the normal cells which are in the interaction with tumoral ones. The present authors attempted to determine the efficacy of the tumor marker CA-125 and HE4 to differentiate the malign cases from the benign adnexal masses. A total of 76 patients with the appropriate criteria were included in the study. They were divided into three groups; healthy control group (n=31), ones with benign masses (n=23), and ones with malign ovarian masses (n=22). In the study, when the cut-off values were accepted as 55I U/ml for CA-125 and 150 pM for HE4 in differentiation of benign and malign groups, the sensitivity was found as 59.09%, specificity 91.3%, PPV 86.67% and NPV 70% LR = +6.8. This combination gives one false positive result to every five positive cases which were detected as high. With the combination of CA-125 and HE4, the value of sensitivity was found decreased as expected, although the value of the specificity increased.

Keywords

Tumor markers; HE4; CA-125; Adnexal mass; Ovarian cancer.

Cite and Share

E. Yücel,E. İlter,F.B. Aksungar,A. Çelik,B.H. Peker,E. Şerifsoy,S. Bozkurt. HE4: really a novel biomarker for ovarian cancer?. European Journal of Gynaecological Oncology. 2017. 38(1);59-64.

References

[1] Disaia P.J., Creasman W.T.: “The adnexal mass and early ovarian cancer”. In: DiSaia P.J., Creasman W.T. (eds). Clinical gynecologic oncology. 7thed. St Louis: Mosby Co., 2007, 282.

[2] “Cancer incidence in Sweden. Annual report 1996”. Stockholm: Swedish Cancer Registry, Centre for Epidemiology National Board of Health and Welfare, 1996.

[3] Andersen E.S., Knudsen A., Rix P., Johansen B.: “Risk of malignancy index in the preoperative evaluation of patients with adnexal masses”. Gynecol. Oncol., 2003, 90, 109.

[4] Benedet J.L., Hacker N.F., Ngan H.Y.S.: “Staging classifications and clinical practice guidelines of gynaecologic cancers”. Int. J. Gynecol. Obstet., 2000, 70, 207.

[5] Van Nagel J.R.: “Tumor markers in ovarian cancer”. Clin. Obstet. Gynecol., 1983, 10, 197.

[6] Bast R.C., Klug T.L., Schaetzl E., Levin P., Niloff J.M., Graber T.F.: “Monitoring human ovarian carcinoma with a combination of CA- 125, CA 19.9, and CEA”. Am. J. Obstet. Gynecol., 1984, 149, 47.

[7] Bast R.C., Feenay N., Lazarus H.: “Reactivity of a monocional antibody with human ovarian carcinoma”. J. Clin. Invest., 1981, 68, 1331.

[8] Wang K., Gan L., Jeffery E., Gayle M., Gown A.M., Skelly M., et al.: “Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray”. Gene, 1999, 229, 101.

[9] Galgano M.T., Hampton G.M., Frierson H.F.: “Comprehensive analysis of HE4 expression in normal and malignant human tissues”. Mod. Pathol., 2006, 19, 847.

[10] Hellstorm I., Raycraft J., Hayden-Ledbetter M., Ledbetter A.J., Schummer M., Mcintosh M., et al.: “The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma”. Cancer Res., 2003, 63, 3695.

[11] Moore R.G., Brown A.K., Miller M.C., Skates S., Allard W.J., Verch T., et al.: “The use of multiple novel Tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass”. Gynecol. Oncol., 2007, 108, 402.

[12] Moore R.G., Brown A.K., Miller M.C., Badgwell G., Lu Z., Allard W.J., et al.: “Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus”. Gynecol. Oncol., 2008, 110, 196.

[13] Andersen R.M., Goff B.A., Lowe K.A., Scholler N., Bergan L., Drecsher C.W., et al.: “Use of a Symptom Index, CA-125, and HE4 to predict ovarian cancer”. Gynecol. Oncol., 2010, 116, 378.

[14] Rottem S., Levit N., Thaler I., Yoffe N., Branshtein M., Monor D., et al.: “Clasification of ovarian lesions by high-Frequency tranvaginal sonography”. J. Clin. Ultrasound, l990, 18, 359.

[15] Jemal A., Siegel R., Ward E., Murray T., Xu J., Thun J.M.: “Cancer statistics, 2007”. CA Cancer J. Clin., 2007, 57, 43.

[16] Paek J., Lee S.H., Yim G.W., Lee M., Kim Y.J., Nam E.J., et al.: “Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2011, 158, 338.

[17] O’Connell G.J., Ryan E., Murphy K.J., Prefontaine M.: “Predictive value of CA 125 for ovarian carcinoma in patients presenting with pelvic masses”. Obstet. Gynecol., 1987, 70, 930.

[18] Milojkovic M., Hrgovic Z., Hrgovic I., Jonat W., Maass N., Bukovic D.: “Significance of CA-125 serum level in discrimination between benign and malignant masses in the pelvis”. Arch. Gynecol. Obstet., 2004, 269, 176.

[19] Moore R.G., McMeekin S.D., Brown A.K., DiSilvestro P., Miller M.C., Allard W.J., et al.: “A novel multiple marker bioassay utilizing HE-4 and CA-125 for the prediction of ovarian cancer in patients with a pelvic mass”. Gynecol. Oncol., 2009, 112, 40.

[20] Brioshi P.A., Irion O., Kraver F.: “Serum CA-125 in epitelial cancer. A longitudinal study”. Br. J. Obstet. Gynaecol., 1987, 94, 196.

[21] Jacobs I., Davies A.P., Bridges J., Stabile I., Fay T., Lower A., et al.: “Prevalance screening for ovarian cancer in postmenopausal women by CA-125 measurement and ultrasonography”. BMJ, 1993, 306, 1030.

[22] Einhorn N., Sjövall K., Knapp R.C., Hall P., Scully E., Bast R.C., et al.: “Prospective evaluation of serum CA-125 levels for the early detection of ovarian cancer”. Obstet. Gynecol., 1992, 80, 14.

[23] Jacobs I., Bridges J., Reynolds J., Stabile I., Kemsley P., Grudzinskas J., et al.: “Multimodal approach to screning for ovarian cancer”. Lancet, 1988, 1, 268.

[24] Scholler N., Fu N., Yang Y., Ye Z., Goodman G.E., Hellström K.E., et al.: “Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma”. Proc. Natl. Acad. Sci. USA, 1999, 96, 11531.

[25] Mok S.C., Chao J., Skates S., Wong K.K., Yiu G.K., Muto M.G., et al.: “Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology”. J. Natl. Cancer. Inst., 2001, 93, 1458.

[26] Kim J.H., Skates S.J., Uede T., Wong K.K., Schorge J.O., Feltmate C.M., et al.: “Osteopontin as a potential diagnostic biomarker for ovarian cancer”. JAMA, 2002, 287, 1671.

[27] Hwang J., Na S., Lee H., Lee D.: “Correlation between preoperative serum levels of five biomarkers and relationships between these biomarkers and cancer stage in epithelial overian cancer”. J. Gynecol. Oncol., 2009, 20, 169.

[28] Diamandis E.P., Yousef G.M., Soosaipillai A.R., Bunting P.: “Human kallikrein 6 (zyme/proteaseM/neurosin): a new serum biomarker of ovarian carcinoma”. Clin. Biochem., 2000, 33, 579.

[29] Baron A.T., Lafky J.M., Boardman C.H., Balasubramaniam S., Suman V.J., Podart K.C., et al.: “Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer”. Cancer Epidemiol. Biomarkers Prev., 1999, 8, 129.

[30] Cho Y., Kim D., Kim J., Kim Y., Kim K., Nam J.: “Mutational analysis of KRAS, BRAF, and TP53 genes of ovarian serous carcinomas in Korean women”. Yonsei Med. J., 2009, 50, 266.

[31] Kim J.Y., Bae B., Kim K.S., Shin E., Park K.: “Osteopontin, CD44, and NFkappaB expression in gastric adenocarcinoma”. Cancer Res. Treat., 2009, 41, 29.

[32] Kirchhoff C., Habben I., Ivell R., Krull N.: “A major human epididymis- specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors”. Biol. Reprod., 1991, 45, 350.

[33] Kirchhoff C.: “Molecular characterization of epididymal proteins”. Rev. Reprod., 1998, 3, 86.

[34] Wang S., Dong L., Li H., Wang M.: “The application of HE-4 in diagnosis of gynecological pelvic malignant tumor”. Clin. Oncol. Cancer Res., 2009, 6, 72.

[35] Huhtinen K., Suvitie P., Hiissa J., Junnila J., Huvila J., Kujari H., et al.: “Serum HE-4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts”. Br. J. Cancer, 2009, 100, 1315.

[36] Havrilesky L.J., Whitehead C.M., Rubatt J.M., Cheek R.L., Groelke J., He Q., et al.: “Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence”. Gynecol. Oncol., 2008, 110, 374.

[37] Scholler N., Crawford M., Sato A., Drescher C.W., O’Braint K.C., Kiviat N., et al.: “Bead-based ELISA for validation of ovarian cancer early detection markers”. Clin. Cancer Res., 2006, 12, 2117.

[38] Galgano M.T., Hampton G.M., Frierson H.F. Jr.: “Comprehensive analysis of HE4 expression in normal and malignant human tissues”. Mod. Pathol., 2006, 19, 847.

[39] Bingle L., Cross S.S., High A.S., Wallace W.A., Rassi D., Yuan G., et al.: “WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development ofadenocarcinomas of the lung”. Respir. Res., 2006, 7, 61.

[40] Xi Z., LinLin M., Ye T.: “Human epididymis protein 4 is a biomarker for transitiona cell carcinoma in the urinary system”. J. Clin. Lab. Anal., 2009, 23, 357.

[41] Li J., Dowdy S., Tipton T., Podratz K., Lu W.G., Xie X., et al.: “HE4 as a biomarker for ovarian and endometrial cancer management”. Expert Rev. Mol. Diagn., 2009, 9, 555.


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