International Journal of Cancer Management

Published by: Kowsar

A Survey on the Role of Cancer Antigen 125 (CA125), Human Epididymis Protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA), and Risk of Malignancy Index (RMI) in Pelvic Mass

Mojgan Karimi–Zarchi 1 , 2 , Nadereh Behtash 3 , Azamsadat Mousavi 3 , Fazemeh Ghaem Maghami 3 , Mitra Moddares Gilani 3 , Zohreh Chiti 3 , Esmat Barouti 3 , Elnaz Sheikhpour 4 and Atiyeh Javaheri 5 , *
Authors Information
1 Department of Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Recurrent Abortion Research Center, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3 Department of Gynecology, Tehran University of Medical Sciences, Tehran, Iran
4 Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Science, Yazd, Iran
5 Department of Obstetrics and Gynecology, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Article information
  • International Journal of Cancer Management: December 31, 2018, 11 (12); e79189
  • Published Online: December 17, 2018
  • Article Type: Review Article
  • Received: May 17, 2018
  • Revised: December 10, 2018
  • Accepted: December 10, 2018
  • DOI: 10.5812/ijcm.79189

To Cite: Karimi–Zarchi M, Behtash N, Mousavi A, Ghaem Maghami F, Moddares Gilani M, et al. A Survey on the Role of Cancer Antigen 125 (CA125), Human Epididymis Protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA), and Risk of Malignancy Index (RMI) in Pelvic Mass, Int J Cancer Manag. 2018 ; 11(12):e79189. doi: 10.5812/ijcm.79189.

Copyright © 2018, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Karimi-Zarchi M, Mojaver SP, Rouhi M, Hekmatimoghaddam SH, Moghaddam RN, Yazdian-Anari P, et al. Diagnostic value of the risk of malignancy index (RMI) for detection of pelvic malignancies compared with pathology. Electron Physician. 2015;7(7):1505-10. doi: 10.19082/1505. [PubMed: 26767105]. [PubMed Central: PMC4700897].
  • 2. Alanbay I, Akturk E, Coksuer H, Ercan M, Karasahin E, Dede M, et al. Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor. Gynecol Endocrinol. 2012;28(6):478-82. doi: 10.3109/09513590.2011.633663. [PubMed: 22122561].
  • 3. Bouzari Z, Yazdani S, Shirkhani Kelagar Z, Abbaszadeh N. Risk of malignancy index as an evaluation of preoperative pelvic mass. Caspian J Intern Med. 2011;2(4):331-5. [PubMed: 24551441]. [PubMed Central: PMC3895832].
  • 4. Bast RC Jr, Skates S, Lokshin A, Moore RG. Differential diagnosis of a pelvic mass: Improved algorithms and novel biomarkers. Int J Gynecol Cancer. 2012;22 Suppl 1:S5-8. doi: 10.1097/IGC.0b013e318251c97d. [PubMed: 22543921]. [PubMed Central: PMC3389992].
  • 5. Lokich E, Palisoul M, Romano N, Craig Miller M, Robison K, Stuckey A, et al. Assessing the risk of ovarian malignancy algorithm for the conservative management of women with a pelvic mass. Gynecol Oncol. 2015;139(2):248-52. doi: 10.1016/j.ygyno.2015.09.010. [PubMed: 26364809]. [PubMed Central: PMC4868067].
  • 6. Chen X, Zhou H, Chen R, He J, Wang Y, Huang L, et al. Development of a multimarker assay for differential diagnosis of benign and malignant pelvic masses. Clin Chim Acta. 2015;440:57-63. doi: 10.1016/j.cca.2014.11.013. [PubMed: 25447698].
  • 7. Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian carcinoma diagnosis. Cancer. 2000;89(10):2068-75. [PubMed: 11066047].
  • 8. Park JW, Park JH, Song ES, Lee BI, Lee JH, Kim KW, et al. Four risk of malignancy indices in evaluation of pelvic masses. Korean J Obstet Gynecol. 2012;55(9):636-43. doi: 10.5468/KJOG.2012.55.9.636.
  • 9. Schutter EM, Sohn C, Kristen P, Mobus V, Crombach G, Kaufmann M, et al. Estimation of probability of malignancy using a logistic model combining physical examination, ultrasound, serum CA 125, and serum CA 72-4 in postmenopausal women with a pelvic mass: An international multicenter study. Gynecol Oncol. 1998;69(1):56-63. doi: 10.1006/gyno.1998.4942. [PubMed: 9570999].
  • 10. Duffy MJ, Bonfrer JM, Kulpa J, Rustin GJ, Soletormos G, Torre GC, et al. CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use. Int J Gynecol Cancer. 2005;15(5):679-91. doi: 10.1111/j.1525-1438.2005.00130.x. [PubMed: 16174214].
  • 11. Davis HM, Zurawski VR Jr, Bast RC Jr, Klug TL. Characterization of the CA 125 antigen associated with human epithelial ovarian carcinomas. Cancer Res. 1986;46(12 Pt 1):6143-8. [PubMed: 2430690].
  • 12. Yin BW, Lloyd KO. Molecular cloning of the CA125 ovarian cancer antigen: Identification as a new mucin, MUC16. J Biol Chem. 2001;276(29):27371-5. doi: 10.1074/jbc.M103554200. [PubMed: 11369781].
  • 13. Karimi-Zarchi M, Dehshiri-Zadeh N, Sekhavat L, Nosouhi F. Correlation of CA-125 serum level and clinico-pathological characteristic of patients with endometriosis. Int J Reprod Biomed (Yazd). 2016;14(11):713-8. [PubMed: 28008424]. [PubMed Central: PMC5153578].
  • 14. Gilani MM, Zarchi MK, Ghaemmaghami F, Behtash N, Mousavi AS, Ansaripoor S. RETRACTED: A study to evaluate the utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer. Gyncol Oncol. 2007;105(3):780-3.
  • 15. Simmons AR, Baggerly K, Bast Jr RC. The emerging role of HE4 in the evaluation of advanced epithelial ovarian and endometrial carcinomas. Oncol (Williston Park, NY). 2013;27(6):548–556. [PubMed: 23909069].
  • 16. 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(13):3695-700. [PubMed: 12839961].
  • 17. Richards A, Herbst U, Manalang J, Pather S, Saidi S, Tejada-Berges T, et al. HE4, CA125, the risk of malignancy algorithm and the risk of malignancy index and complex pelvic masses-a prospective comparison in the pre-operative evaluation of pelvic masses in an Australian population. Aust N Z J Obstet Gynaecol. 2015;55(5):493-7. doi: 10.1111/ajo.12363. [PubMed: 26172511].
  • 18. Pitynski K, Sporek A, Lipinska I, Banas T, Ludwin A, Balajewicz-Nowak M. Significance of adding progesterone to the risk of ovarian malignancy algorithm for early stage ovarian cancer detection in patients with a pelvic mass: A single-center case-control study. Taiwan J Obstet Gynecol. 2015;54(6):766-72. doi: 10.1016/j.tjog.2015.10.006. [PubMed: 26701000].
  • 19. LeBleu VS, Teng Y, O'Connell JT, Charytan D, Muller GA, Muller CA, et al. Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis. Nat Med. 2013;19(2):227-31. doi: 10.1038/nm.2989. [PubMed: 23353556]. [PubMed Central: PMC4457508].
  • 20. Galgano MT, Hampton GM, Frierson HF Jr. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 2006;19(6):847-53. doi: 10.1038/modpathol.3800612. [PubMed: 16607372].
  • 21. O'Neal RL, Nam KT, LaFleur BJ, Barlow B, Nozaki K, Lee HJ, et al. Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. Hum Pathol. 2013;44(5):734-42. doi: 10.1016/j.humpath.2012.07.017. [PubMed: 23084584]. [PubMed Central: PMC3556378].
  • 22. Kamei M, Yamashita S, Tokuishi K, Hashioto T, Moroga T, Suehiro S, et al. HE4 expression can be associated with lymph node metastases and disease-free survival in breast cancer. Anticancer Res. 2010;30(11):4779-83. [PubMed: 21115941].
  • 23. Granato T, Porpora MG, Longo F, Angeloni A, Manganaro L, Anastasi E. HE4 in the differential diagnosis of ovarian masses. Clin Chim Acta. 2015;446:147-55. doi: 10.1016/j.cca.2015.03.047. [PubMed: 25892674].
  • 24. Yamamoto Y, Yamada R, Oguri H, Maeda N, Fukaya T. Comparison of four malignancy risk indices in the preoperative evaluation of patients with pelvic masses. Eur J Obstet Gynecol Reprod Biol. 2009;144(2):163-7. doi: 10.1016/j.ejogrb.2009.02.048. [PubMed: 19327881].
  • 25. Akturk E, Karaca RE, Alanbay I, Dede M, Karasahin E, Yenen MC, et al. Comparison of four malignancy risk indices in the detection of malignant ovarian masses. J Gynecol Oncol. 2011;22(3):177-82. doi: 10.3802/jgo.2011.22.3.177. [PubMed: 21998760]. [PubMed Central: PMC3188716].
  • 26. Manjunath AP, Pratapkumar , Sujatha K, Vani R. Comparison of three risk of malignancy indices in evaluation of pelvic masses. Gynecol Oncol. 2001;81(2):225-9. doi: 10.1006/gyno.2001.6122. [PubMed: 11330953].
  • 27. Morgante G, la Marca A, Ditto A, De Leo V. Comparison of two malignancy risk indices based on serum CA125, ultrasound score and menopausal status in the diagnosis of ovarian masses. Br J Obstet Gynaecol. 1999;106(6):524-7. [PubMed: 10426607].
  • 28. 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(2):402-8. doi: 10.1016/j.ygyno.2007.10.017. [PubMed: 18061248].
  • 29. Cho HY, Kyung MS. Serum CA19-9 as a predictor of malignancy in primary ovarian mucinous tumors: A matched case-control study. Med Sci Monit. 2014;20:1334-9. doi: 10.12659/MSM.890954. [PubMed: 25073801]. [PubMed Central: PMC4117678].
  • 30. Karimi-Zarchi M, Baghdadabad A, Baghdadabad MR, Zahir Sh T, Abadi RD, Teimoori S, et al. Evaluation of serum CA 125 level and its relation to surgical, histopathologic and ultrasonographic findings in patients with pelvic mass. Eur J Gynaecol Oncol. 2014;35(1):67-71. [PubMed: 24654466].
  • 31. Zhang P, Wang C, Cheng L, Zhang P, Guo L, Liu W, et al. Comparison of HE4, CA125, and ROMA diagnostic accuracy: A prospective and multicenter study for chinese women with epithelial ovarian cancer. Medicine (Baltimore). 2015;94(52). e2402. doi: 10.1097/MD.0000000000002402. [PubMed: 26717395]. [PubMed Central: PMC5291636].
  • 32. Montagnana M, Lippi G, Ruzzenente O, Bresciani V, Danese E, Scevarolli S, et al. The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. J Clin Lab Anal. 2009;23(5):331-5. doi: 10.1002/jcla.20340. [PubMed: 19774626].
  • 33. Abdel-Azeez HA, Labib HA, Sharaf SM, Refai AN. HE4 and mesothelin: Novel biomarkers of ovarian carcinoma in patients with pelvic masses. Asian Pac J Cancer Prev. 2010;11(1):111-6. [PubMed: 20593939].
  • 34. Hamed EO, Ahmed H, Sedeek OB, Mohammed AM, Abd-Alla AA, Abdel Ghaffar HM. Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response. Diagn Pathol. 2013;8:11-4. doi: 10.1186/1746-1596-8-11. [PubMed: 23343214]. [PubMed Central: PMC3621278].
  • 35. 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 a pelvic mass. Gynecol Oncol. 2009;112(1):40-6. doi: 10.1016/j.ygyno.2008.08.031. [PubMed: 18851871]. [PubMed Central: PMC3594094].
  • 36. Asher V, Hammond R, Duncan TJ. Pelvic mass associated with raised CA 125 for benign condition: A case report. World J Surg Oncol. 2010;8(28):1-10. doi: 10.1186/1477-7819-8-28. [PubMed: 20398372]. [PubMed Central: PMC2861664].
  • 37. Sandri MT, Bottari F, Franchi D, Boveri S, Candiani M, Ronzoni S, et al. Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: Correlation with pathological outcome. Gynecol Oncol. 2013;128(2):233-8. doi: 10.1016/j.ygyno.2012.11.026. [PubMed: 23200911].
  • 38. Romagnolo C, Leon AE, Fabricio ASC, Taborelli M, Polesel J, Del Pup L, et al. HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) as diagnostic tools for ovarian cancer in patients with a pelvic mass: An Italian multicenter study. Gynecol Oncol. 2016;141(2):303-11. doi: 10.1016/j.ygyno.2016.01.016.
  • 39. Yanaranop M, Anakrat V, Siricharoenthai S, Nakrangsee S, Thinkhamrop B. Is the risk of ovarian malignancy algorithm better than other tests for predicting ovarian malignancy in women with pelvic masses? Gynecol Obstet Invest. 2017;82(1):47-53. doi: 10.1159/000446238. [PubMed: 27197526].
  • 40. Dayyani F, Uhlig S, Colson B, Simon K, Rolny V, Morgenstern D, et al. Diagnostic performance of risk of ovarian malignancy algorithm against CA125 and HE4 in connection with ovarian cancer: A meta-analysis. Int J Gynecol Cancer. 2016;26(9):1586-93. doi: 10.1097/IGC.0000000000000804. [PubMed: 27540691].
  • 41. Al Musalhi K, Al Kindi M, Al Aisary F, Ramadhan F, Al Rawahi T, Al Hatali K, et al. Evaluation of HE4, CA-125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) in the preoperative assessment of patients with adnexal mass. Oman Med J. 2016;31(5):336-44. doi: 10.5001/omj.2016.68. [PubMed: 27602187]. [PubMed Central: PMC4996955].
  • 42. Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller MC, Allard WJ, et al. Comparison of a novel multiple marker assay vs the risk of malignancy index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol. 2010;203(3):228 e1-6. doi: 10.1016/j.ajog.2010.03.043. [PubMed: 20471625]. [PubMed Central: PMC3594101].
  • 43. van den Akker PA, Aalders AL, Snijders MP, Kluivers KB, Samlal RA, Vollebergh JH, et al. Evaluation of the risk of malignancy index in daily clinical management of adnexal masses. Gynecol Oncol. 2010;116(3):384-8. doi: 10.1016/j.ygyno.2009.11.014. [PubMed: 19959215].
  • 44. Hakansson F, Hogdall EV, Nedergaard L, Lundvall L, Engelholm SA, Pedersen AT, et al. Risk of malignancy index used as a diagnostic tool in a tertiary centre for patients with a pelvic mass. Acta Obstet Gynecol Scand. 2012;91(4):496-502. doi: 10.1111/j.1600-0412.2012.01359.x. [PubMed: 22229703].
  • 45. Karlsen MA, Sandhu N, Hogdall C, Christensen IJ, Nedergaard L, Lundvall L, et al. Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 2012;127(2):379-83. doi: 10.1016/j.ygyno.2012.07.106. [PubMed: 22835718].
  • 46. Bandiera E, Romani C, Specchia C, Zanotti L, Galli C, Ruggeri G, et al. Serum human epididymis protein 4 and risk for ovarian malignancy algorithm as new diagnostic and prognostic tools for epithelial ovarian cancer management. Cancer Epidemiol Biomarkers Prev. 2011;20(12):2496-506. doi: 10.1158/1055-9965.EPI-11-0635. [PubMed: 22028406]. [PubMed Central: PMC3237732].
  • 47. Winarto H, Laihad BJ, Nuranna L. Modification of cutoff values for HE4, CA125, the risk of malignancy index, and the risk of malignancy algorithm for ovarian cancer detection in Jakarta, Indonesia. Asian Pac J Cancer Prev. 2014;15(5):1949-53. [PubMed: 24716917].
  • 48. Ortiz-Munoz B, Aznar-Oroval E, Garcia Garcia A, Covisa Peris A, Perez Ballestero P, Sanchez Yepes M, et al. HE4, Ca125 and ROMA algorithm for differential diagnosis between benign gynaecological diseases and ovarian cancer. Tumour Biol. 2014;35(7):7249-58. doi: 10.1007/s13277-014-1945-6. [PubMed: 24771264].
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