The Use of Human Epididymis 4 and Cancer Antigen 125 Tumor Markers in the Benign or Malignant Differential Diagnosis of Pelvic or Adnexal Masses

Year 2017, Volume: 34 Issue: 2, 156 - 162, 01.03.2017

Zehra Nihal Dolgun Canan Kabaca Ateş Karateke Cem İyibozkurt Cihan İnan Ahmet Salih Altıntaş Cihan Karadağ

Abstract

Background: Ovarian cancer is one of the highest mortality cancers in gynaecology. Discrimination of benign masses from malignant ones may sometimes become a challenge for the clinician since there is not a reliable tumour marker, thus some unnecessary, highly morbid operations can be performed. Aims: To explore the efficacy of human epididymis 4 (HE 4) and cancer antigen 125 (CA 125) markers in differentiating malignant and benign pelvic masses of ovarian origin and to identify the cut-off points for those markers. Study Design: Prospective study. Methods: Fifty-one patients who were diagnosed and planned to undergo surgery for ovarian mass between June 2008 and December 2008 were enrolled into this study. Preoperative venous blood samples were taken and frozen for marker investigation and final diagnoses were concluded by histopathological examination. After recruitment of all cases CA 125 and HE 4 levels were evaluated. Results: The statistical analysis did not indicate any statistically significant difference between the CA 125 levels of the patients with malignant and benign adnexal masses (p=0.105). The HE 4 levels of the patients with malignant adnexal masses were higher at a statistically significant level compared to the patients with benign adnexal masses (p=0.002). For HE 4 tumour marker and at the cut-off point of >25 pM, sensitivity was 1, specificity 0.40, positive cut-off value 0.19, negative cut-off value 1, accuracy 0.47 and positive likelihood ratio 1.65. Conclusion: Human epididymis 4 is a better diagnostic tool than CA 125 in benign-malignant discrimination of adnexal masses. The cut-off value of 25 pmol/L for human epididymis 4 will contribute to providing proper guidance to patients with adnexal masses and applying the proper treatment method.

Keywords

Tumour marker, ovarian cancer, adnexal mass, human epididymis 4, cancer antigen 125

References

• 1. Al-Shukri M, Mathew M, Al-Ghafri W, Al-Kalbani M, Al-Kharusi L, Gowri V. A clinicopathological study of women with adnexal masses presenting with acute symptoms. Ann Med Health Sci Res 2014;4:286-8.
• 2. BerekJS, Crum C, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2015;131(Suppl 2):111-22.
• 3. Bankhead CR, Kehoe ST, Austoker J. Symptoms associated with diagnosis of ovarian cancer: a systematic review. BJOG 2005;112:857-65.
• 4. Lataifeh I, Marsden DE, Robertson G, Gebski V, Hacker NF. Presenting symptoms of epithelial ovarian cancer. Aust N Z J Obstet Gynaecol 2005;45:211-4.
• 5. Kabaca C, Dolgun ZN, Telci A, Karateke A. Serum human epididymis protein 4 (HE 4) in the differential diagnosis of peritoneal tuberculosis: A report of two cases. Balkan Med J 2014;31:270-1.
• 6. Hellström 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;63:3695-700.
• 7. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011;305:2295-303.
• 8. Menon U, Skates SJ, Lewis S, Rosenthal AN, Rufford B, Sibley K, et al. Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol 2005;23:7919-26.
• 9. Fujiwara HI, Suzuki M, Takeshima N, Takizawa K, Kimura E, Nakanishi T, et al. Evaluation of human epididymis protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA) as diagnostic tools of type I and type II epithelial ovarian cancer in Japanese women. Tumour Biol 2015;36:1045- 53.
• 10. Bast RC Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981;68:1331-7.
• 11. Tuxen MK. Tumor marker CA 125 in ovarian cancer. J Tumor Markers Oncol 2001;16:49-68.
• 12. Kobayashi H, Yamada Y, Sado T, Sakata M, Yoshida S, Kawaguchi R, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 2008;18:414-20.
• 13. Skates SJ, Xu FJ, Yu YH, Sjövall K, Einhorn N, Chang Y, et al. Toward an optimal algorithm for ovarian cancer screening with longitudinal tumor markers. Cancer 1995;76(10 Suppl):2004-10.
• 14. Bouchard D, Morisset D, Bourbonnais Y, Tremblay GM. Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol 2006;7:167-74.
• 15. Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, et al. A novel multiple marker bioassay utilizing HE4 and CA 125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 2009;112:40-6.
• 16. Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, 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 2008;108:402-8.
• 17. Piovano E, Attamante L, Macchi C, Cavallero C, Romagnolo C, Maggino T, et al. The role of HE4 in ovarian cancer follow-up: a review. Int J Gynecol Cancer 2014;24:1359-65.
• 18. Chung SH, Lee SY, Ju W, Kim SC. Clinical efficacy of serum human epididymis protein 4 as a diagnostic biomarker of ovarian cancer: A pilot study. Obstet Gynecol Sci 2013;56:234-41.
• 19. Michalak M, Gąsiorowska E, Markwitz EN. Diagnostic value of CA 125, HE4, ROMA and logistic regression model in pelvic mass diagnostics - our experience. Ginekol Pol 2015;86:256-61.