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

  • Winarto, Hariyono ;
  • Laihad, Bismarck Joel ;
  • Nuranna, Laila
  • Published : 2014.03.01


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 modified cutoff values for Ca125, 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 modified by using logistic regression model. The modified cutoff values were compared to the standard cutoff values in terms of sensitivity, specificity, and accuracy. Results: The modified cutoff value of CA125, HE4, RMI score and ROMA were 165.2 U/mL, 103.4 pM, 368.7, 28/54. The sensitivity and specificity of the modified 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 specificity 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 modified 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 modified 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.


Ovarian cancer;CA125;human epidydimis protein 4;ROMA;RMI;tumor marker cutoff values


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