Comparison of Risk of Ovarian Malignancy Algorithm and cancer antigen 125 to discriminate between benign ovarian tumor and early‑stage ovarian cancer according to imaging tumor subtypes

Lee,Young‑Jae; Kim,Yong‑Man; Kang,Ji‑Sik; Nam,So‑Hyun; Kim,Dae‑Yeon; Kim,Young‑Tak

doi:10.3892/ol.2020.11629

Comparison of Risk of Ovarian Malignancy Algorithm and cancer antigen 125 to discriminate between benign ovarian tumor and early‑stage ovarian cancer according to imaging tumor subtypes

Authors:
- Young‑Jae Lee
- Yong‑Man Kim
- Ji‑Sik Kang
- So‑Hyun Nam
- Dae‑Yeon Kim
- Young‑Tak Kim
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Affiliations: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
Published online on: May 14, 2020 https://doi.org/10.3892/ol.2020.11629
Pages: 931-938

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Abstract

The present study aimed to compare the accuracy of the Risk of Ovarian Malignancy Algorithm (ROMA) and cancer antigen (CA)125 to discriminate between benign ovarian tumors and early‑stage ovarian cancer according to imaging tumor subtypes associated with post‑operative histopathological findings. A total of 1,207 patients who were assessed using the ROMA test due to suspected early‑stage ovarian cancer and underwent surgery at Asan Medical Center (Seoul, Korea) between September 2014 and March 2018 were identified. A total of 981 patients who met the inclusion criteria were included in the retrospective analysis. Among the 981 subjects, 816 had benign tumors, 90 had malignant tumors and 75 had borderline tumors. Of the patients diagnosed with ovarian cancer or borderline tumor, 47.3% were judged as high‑risk by the ROMA test and 58.2% had CA125 levels of >35 U/ml. The specificity and accuracy of ROMA were higher compared with those of CA125 in pre‑menopausal females. However, the superiority of the ROMA test in the identification of malignant ovarian tumors compared with CA125 was only observed in patients with endometriotic‑type tumors but not in any of the other tumor subtypes. In the endometriotic type of ovarian tumor, the superiority of the ROMA test compared to CA125 was confirmed in triage of ovarian tumor. However, the sensitivity and specificity of ROMA and CA125 were similar for the other tumor types. Therefore, future development of better tumor‑specific biomarkers for triage of ovarian tumor is required.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Bast RC, Feeney M, Lazarus H, Nadler LM, Colvin RB and Knapp RC: Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 68:1331–1337. 1981. View Article : Google Scholar : PubMed/NCBI
3	Sevinc A, Adli M, Kalender ME and Camci C: Benign causes of increased serum CA-125 concentration. Lancet Oncol. 8:1054–1055. 2019. View Article : Google Scholar
4	Medeiros LR, Rosa DD, da Rosa MI and Bozzetti MC: Accuracy of CA 125 in the diagnosis of ovarian tumors: A quantitative systematic review. Eur J Obstet Gynecol Reprod Biol. 142:99–105. 2019. View Article : Google Scholar
5	Engelen MJ, de Bruijn HW, Hollema H, ten Hoor KA, Willemse PH, Aalders JG and van der Zee AG: Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors. Gynecol Oncol. 78:16–20. 2019. View Article : Google Scholar
6	Simmons AR, Baggerly K and Bast RC: The emerging role of HE4 in the evaluation of epithelial ovarian and endometrial carcinomas. Oncology (Williston Park). 27:548–556. 2019.
7	Lu R, Sun X, Xiao R, Zhou L, Gao X and Guo L: Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. Biochem Biophys Res Commun. 419:274–280. 2012. View Article : Google Scholar : PubMed/NCBI
8	Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, Hassell L, Baldwin RL, Karlan BY and Hood L: Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene. 238:375–385. 1999. View Article : Google Scholar : PubMed/NCBI
9	Granato T, Porpora MG, Longo F, Angeloni A, Manganaro L and Anastasi E: HE4 in the differential diagnosis of ovarian masses. Clin Chim Acta. 446:147–155. 2015. View Article : Google Scholar : PubMed/NCBI
10	Hallamaa M, Suvitie P, Huhtinen K, Matomäki J, Poutanen M and Perheentupa A: Serum HE4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women. Gynecol Oncol. 125:667–672. 2012. View Article : Google Scholar : PubMed/NCBI
11	Moore RG, Miller MC, Eklund EE, Lu H, Bast RC and Lambert-Messerlian G: Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age. Am J Obstet Gynecol. 206:349.e1–349.e7. 2012. View Article : Google Scholar
12	Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, Gajewski W, Kurman R, Bast RC Jr and Skates SJ: A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 112:40–46. 2009. View Article : Google Scholar : PubMed/NCBI
13	Moore RG, Miller MC, Disilvestro P, Landrum LM, Gajewski W, Ball JJ and Skates SJ: Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol. 118:280–288. 2011. View Article : Google Scholar : PubMed/NCBI
14	Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR and Hecht JL: Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 65:2162–2169. 2005. View Article : Google Scholar : PubMed/NCBI
15	Kim B, Park Y, Kim B, Ahn HJ, Lee KA, Chung JE and Han SW: Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer. J Clin Lab Anal. 33:e226242019. View Article : Google Scholar : PubMed/NCBI
16	Molina R, Escudero JM, Augé JM, Filella X, Foj L, Torné A, Lejarcegui J and Pahisa J: HE4 a novel tumour marker for ovarian cancer: Comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumor Biol. 32:1087–1095. 2011. View Article : Google Scholar
17	Romeo V, Framarino Dei Malatesta M, Nudo F, Simonelli L, Derme M and Berloco PB: Is HE4 serum level a valid screening test in women candidates for kidney transplant? A case report and a review of literature. Clin Ter. 165:e162–e165. 2014.PubMed/NCBI
18	Anton C, Carvalho FM, Oliveira EI, Maciel GAR, Baracat EC and Carvalho JP: A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. Clinics (Sao Paulo). 67:437–441. 2012. View Article : Google Scholar : PubMed/NCBI
19	Mutch DG and Prat J: 2014 FIGO staging for ovarian, fallopian tube and peritoneal cancer. Gynecol Oncol. 133:401–404. 2014. View Article : Google Scholar : PubMed/NCBI
20	Ruggeri G, Bandiera E, Zanotti L, Belloli S, Ravaggi A, Romani C, Bignotti E, Tassi RA, Tognon G, Galli C, et al: HE4 and epithelial ovarian cancer: Comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta. 412:1447–1453. 2011. View Article : Google Scholar : PubMed/NCBI
21	Lenhard M, Stieber P, Hertlein L, Kirschenhofer A, Fürst S, Mayr D, Nagel D, Hofmann K, Krocker K and Burges A: The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses. Clin Chem Lab Med. 49:2081–2088. 2011. View Article : Google Scholar : PubMed/NCBI
22	Chan KK, Chen CA, Nam JH, Ochiai K, Wilailak S, Choon AT, Sabaratnam S, Hebbar S, Sickan J, Schodin BA and Sumpaico WW: The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass. Gynecol Oncol. 128:239–244. 2019. View Article : Google Scholar
23	Karlsen MA, Høgdall EV, Christensen IJ, Borgfeldt C, Kalapotharakos G, Zdrazilova-Dubska L, Chovanec J, Lok CA, Stiekema A, Mutz-Dehbalaie I, et al: A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer-An international multicenter study in women with an ovarian mass. Gynecol Oncol. 138:640–646. 2015. View Article : Google Scholar : PubMed/NCBI
24	Dayyani F, Uhlig S, Colson B, Simon K, Rolny V, Morgenstern D and Schlumbrecht M: Diagnostic performance of risk of ovarian malignancy algorithm against CA125 and HE4 in connection with ovarian cancer: A Meta-analysis. Int J Gynecol Cancer. 26:1586–1593. 2019. View Article : Google Scholar
25	Wolman I: Berek and Novak's Gynecology 15th Edition. J Obstet Gynecol India. 2014.