Asian Pacifc Journal of Cancer Prevention, Vol 15, 2014 1949 DOI:http://dx.doi.org/10.7314/APJCP.2014.15.5.1949 Cutoff Values for HE4, CA125, RMI, and ROMA for Ovarian Cancer Detection in Indonesia Asian Pac J Cancer Prev, 15 (5), 1949-1953 Introduction Ovarian cancer is the third most common female malignancy in Indonesia, accounts for 4.27 cases in 100.000 women (Aziz, 2009; Wahidin, 2012). As the second most common gynecologic malignancy worldwide, the majority of them are epithelial types (Boyle, 2008; Hennessy, 2009). Since there is no screening method, ovarian cancer is often diagnosed when the patients already have had complaints, or in advanced stages. This condition brings diffculty and complexity of therapy that consequently leads to poorer prognosis (Havrilesky et al., 2008). There are some biomarkers and scoring systems that are commonly used to predict malignancy of epithelial ovarian tumor (Bian et al., 2013; Yavuzcan et al., 2013) . However, several studies on these biomarkers showed different conclusions. Rosen et al used CA125 as the main biomarker in detecting ovarian malignancy and concluded Division of Gynecology Oncology, Department of Obstetrics Gynecology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia *For correspondence: hariyonow@gmail.com Abstract Background: CA125 and HE4 are used in calculating Risk of Malignancy Algorithm (ROMA); and Risk of Malignancy Index (RMI). However, studies showed that normal levels of CA125, and HE4 differ among ethnicities such as between Asians and Caucasians, thus affecting the accuracy of the RMI score and ROMA in predicting ovarian malignancy. This study aimed to determine whether new or modifed cutoff values for Ca- 125, HE4, the RMI score, and ROMA resulted in a better prediction of malignancy compared with the previous or standard ones. Materials and Methods: Serum level of CA125 and HE4 from 128 patients with diagnosis of ovarian tumor that had been collected before surgery at Cipto Mangunkusumo General Hospital (CMH) in Jakarta from November 2010 until May 2011 were reviewed and analysed. The standard cutoff values of these biomarkers, RMI, and ROMA were modifed by using logistic regression model. The modifed cutoff values were compared to the standard cutoff values in terms of sensitivity, specifcity, and accuracy. Results: The modifed cutoff value of CA125, HE4, RMI score and ROMA were 165.2 U/mL, 103.4 pM, 368.7, 28/54. The sensitivity and specifcity of the modifed cutoff values CA125, HE 4, RMI score and ROMA in differentiating benign from malignant and borderline were 67% and 75,4%; 73.1% and 85.2%; 73.1% and 80.3%; and 77.6% and 86.9%. While the sensitivity and specifcity of the standard cutoff value of CA125; HE4; RMI score; and ROMA were 91% and 24.6%; 83.6% and 65%; 80.6% and 65.6%; and 91.0% and 42.6%. The accuracy of modifed cutoff values compared with standard cutoff values were: 71.2% vs 59.3%, 78.9% vs 75% vs, 76.5% vs 73.4%, and 82% vs 67.9%. Conclusions: The new or modifed cutoff values of Ca125, HE4, RMI score and ROMA resulted in higher accuracy compared to the previous or standard ones, at the cost of reduced sensitivity. Keywords: Ovarian cancer - CA125 - human epidydimis protein 4 - ROMA - RMI - tumor marker cutoff values RESEARCH ARTICLE Modifcation of Cutoff Values for HE4, CA125, the Risk of Malignancy Index, and the Risk of Malignancy Algorithm for Ovarian Cancer Detection in Jakarta, Indonesia Hariyono Winarto*, Bismarck Joel Laihad, Laila Nuranna that additional complementary marker to improve the result it still needed (Rosen, 2005). Other studies showed that the usage of HE4 as well as combination of HE4 and CA125 in ROMA and RMI are more superior than CA125 alone or other markers (Moore et al., 2008; 2009; Lin et al., 2012). Overall, different studies resulted in different diagnostic values (sensitivity, specifcity, and accuracy) of each biomarkers (Van Gorp et al., 2011). Other studies also compared normal values of biomarkers such as CA125 and HE4 from one population to another. CA125 level between Asian and Caucasian healthy women are different (Pauler et al., 2001). There is also a difference in HE4 level between Indian and Malay ethnicity (Mokhtar et al., 2012). The differences in level of these biomarkers among ethnicities could make different results in sensitivity and specifcity. Karen et al., suggested an alternative cutoff value for CA125, HE4, and ROMA that results in different sensitivity and specifcity values of each markers (Chan, 2013).