DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20221289

Diagnostic accuracy of HE4 and risk of ovarian malignancy algorithm in prediction of ovarian cancer in patients with pelvic mass: a regional cancer centre experience

Ruchi S. Arora, Shilpa M. Patel, Abhilash V., Priyanka Vemanamandhi

Abstract


Background: The current study was performed with an objective to evaluate the diagnostic accuracy of HE4 (human epididymis protein) and ROMA in prediction of ovarian cancer in patients with pelvic mass and to compare HE4 and ROMA with CA-125, and RMI (risk of malignancy index) for ovarian cancer prediction in women with pelvic mass.

Methods: This was a diagnostic study enrolling 200 patients with pelvic mass who had been scheduled for Primary surgery. Serum HE4 and CA 125 levels were measured. HE4, CA 125 and ROMA, RMI were evaluated for sensitivity, specificity, positive predictive value and negative predictive value. The receiver operating characteristic (ROC) plots were graphed and area under the curve (AUC) values was calculated to investigate the accuracy of each marker for predicting ovarian malignancy.

Results: Overall, ROMA showed the highest accuracy as it correctly classified 139/200 (69.5%) patients compared with 133/200 (66.5%) in HE4 and 109/200 (54.5%) in CA 125 and RMI. There were more patients with benign tumors being correctly identified by HE4 (89/119, 74.7%) and ROMA (74/119, 62.1%), than CA 125 which identified 39/119 (32.7%) patients. In our study in premenopausal women ROMA and HE4 have comparable sensitivity (80%and 75%) but higher specificity (64% and 65%) and NPV (86% and 83%) as compared to CA125 which has sensitivity of (83%) but very low specificity (46%) in differentiating benign from malignant masses. In postmenopausal women, HE4 had highest specificity (88%) and, CA125 has highest sensitivity (86%) in detecting ovarian malignancy.

Conclusions: HE4 and ROMA showed a high specificity, but were less sensitivity than CA-125 and RMI in premenopausal women. However, ROMA is of comparable sensitivity and HE4 has highest specificity as compared to CA125 in postmenopausal women.


Keywords


Risk of ovarian malignancy algorithm, Risk of malignancy index, CA-125, HE4, Ovarian cancer, Pelvic mass

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References


Al Musalhi K, Al Kindi M, Al Aisary F, Ramadhan F, Al Rawahi T, Al Hatali K, Mula-Abed WA. 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.

Amor F, Alcázar JL, Vaccaro H, León M, Iturra A. GI-RADS reporting system for ultrasound evaluation of adnexal masses in clinical practice: a prospective multicenter study. Ultrasound Obstet Gynecol. 2011; 38(4):450-5.

Takiar R, Nadayil D, Nandakumar A. Projections of number of cancer cases in India (2010-2020) by cancer groups. Asian Pacific J Cancer Prev. 2010;11(4):1045-9.

Abdalla N, Winiarek J, Bachanek M, Cendrowski K, Sawicki W. Clinical, ultrasound parameters and tumor marker-based mathematical models and scoring systems in pre-surgical diagnosis of adnexal tumors. Ginekologia Polska. 2016;87(12):824-9.

Rauh-Hain JA, Krivak TC, del Carmen MG, Olawaiye AB. Ovarian cancer screening and early detection in the general population. Rev Obstet Gynecol. 2011; 4(1):15-21

Lee KR, Tavassoli FA, Prat J, Dietel M, Gersell DJ, Karseladze AI. In: pathology and genetics of tumours of the breast and female genital organs. Tavassoli FA, Devilee P, eds. USA: Lyon: IARC Press; 2003:113-61.

Nolen B, Marrangoni A, Velikokhatnaya L, Prosser D, Winans M, Gorelik E, et al. A serum based analysis of ovarian epithelial tumorigenesis. Gynecol Oncol. 2009;112(1):47-54.

Myers ER, Bastian LA, Havrilesky LJ, Kulasingam SL, Terplan MS, Cline KE, et al. Management of adnexal mass: evidence reports/technology assessments no.130. Res Qual Evid Rep Technol Assess. 2006;(130):1-145.

Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990;97:922-9.

Tingulstad S, Hagen B, Skjeldestad FE, Halvorsen T, Nustad K, Onsrud M. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet Gynecol. 1999;93:448-52.

Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, et al. Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996;103:826-31.

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(5):1331-7.

Bast RC, Badgwell D, Lu Z, Marquez R, Rosen D, Liu J. New tumor markers: CA125 and beyond. Int J Gynecol Cancer. 2005;15(3):274-81.

Barbieri RL, Niloff JM, Bast RC Jr, Scaetzl E, Kistner RW, Knapp RC. Elevated serum concentrations of CA-125 in patients with advanced endometriosis. Fertil Steril. 1986;45(5):630-4.

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(2):350-7.

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.

Abdalla N, Winiarek J, Bachanek M, Cendrowski K, Sawicki W. Clinical, ultrasound parameters and tumor marker-based mathematical models and scoring systems in pre-surgical diagnosis of adnexal tumors. Ginekol Pol. 2016;87(12):824-9.

Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, Gajewski W, Kurman R, Bast RC, 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. 2009;112(1):40-6.

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 Obstetrics gynecol. 2010;203(3):228.

Chudecka-Głaz, A.M. ROMA, an algorithm for ovarian cancer. Clin. Chim. Acta 2014;440C:143-51.

Holcomb K, Vucetic Z, Miller MC, Knapp RC. HE4 Offers Superior Specificity in the Differentiation of Benign and Malignant Adnexal Masses in Premenopausal Women. Am J Obstet Gynecol. 2011; 205(4):358.

Holcomb K, Vucetic Z, Miller MC, Knapp RC. HE4 Offers Superior Specificity in the Differentiation of Benign and Malignant Adnexal Masses in Premenopausal Women. Am J Obstet Gynecol. 2011; 205(4):358.

Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100(8):1315-9.

Ferraro S, Braga F, Lanzoni M, Boracchi P, Biganzoli EM, Panteghini M. Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol. 2013; 66(4):273-81.

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.

Oranratanaphan S, Wanishpongpan S, Termrungruanglert W, Triratanachat S. Assessment of Diagnostic Values among CA-125, RMI, HE4, and ROMA for Cancer Prediction in Women with Nonfunctional Ovarian Cysts. Obstet Gynecol Int. 2018;2018:7821574.

Lycke M, Kristjansdottir B, Sundfeldt K. A multicenter clinical trial validating the performance of HE4, CA125, risk of ovarian malignancy algorithm and risk of malignancy index. Gynecol Oncol. 2018; 151(1):159-65.

Anton C, Carvalho FM, Oliveira EI, Maciel GA, Baracat EC, Carvalho JP. A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. Clinics. 2012;67:437-41

Chan KK, Chen CA, Nam JH, Ochiai K, Wilailak S, Choon AT, et al. The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass. Gynecol Oncol. 2013;128:239-44.

Van Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the risk of ovarian malignancy algorithm. Br J Cancer. 2011;104:863-70.

Montagnana M, Danese E, Ruzzenente O, Bresciani V, Nuzzo T, Gelati M, et al. The ROMA (risk of ovarian malignancy algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med. 2011;49:521-5.

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;128:233-8.