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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

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 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.

Keywords

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

References

  1. Nolen B, Velikokhatnaya L, Marrangoni A, et al (2010). Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol, 117, 440-5. https://doi.org/10.1016/j.ygyno.2010.02.005
  2. Yavuzcan A, Caglar M, Ozgu E, et al (2013). Should cutoff values of the risk of malignancy index be changed for evaluation of adnexal masses in Asian and Pacific populations?. Asian Pac J Cancer Prev, 13, 5455-9.
  3. Lin J-Y, Qin J-B, Li X-Y, Dong P, Yin B-D (2012). Diagnostic value of human epididymis protein 4 compared with mesothelin for ovarian cancer: a systematic review and metaanalysis. Asian Pac J Cancer Prev, 13, 5427-32. https://doi.org/10.7314/APJCP.2012.13.11.5427
  4. Mokhtar N, Thevarajah M, Ma N, M I (2012). Human epididymis protein 4 reference intervals in a multiethnic Asian women population. Asian Pac J Cancer Prev, 13, 6391-5. https://doi.org/10.7314/APJCP.2012.13.12.6391
  5. Moore RG, Brown AK, Miller MC, et al (2008). The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 108, 402-8. https://doi.org/10.1016/j.ygyno.2007.10.017
  6. Moore RG, McMeekin DS, Brown AK, et al (2009). A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol, 112, 40-6. https://doi.org/10.1016/j.ygyno.2008.08.031
  7. Pauler DK, Menon U, McIntosh M, et al (2001). Factors influencing serum CA125II levels in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev. 10, 489-93.
  8. Rosen DG, Wang L, Atkinson JN, et al (2005). Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol, 99, 267-77. https://doi.org/10.1016/j.ygyno.2005.06.040
  9. Van Gorp T, Cadron I, Despierre E, et al (2011). HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 104, 863-70. https://doi.org/10.1038/sj.bjc.6606092
  10. Wahidin M, Noviani R, Hermawan S, et al (2012). Populationbased cancer registration in Indonesia. Asian Pac J Cancer Prev, 13, 1709-10. https://doi.org/10.7314/APJCP.2012.13.4.1709
  11. Chang X, Ye X, Dong L, et al (2011). Human epididymis protein 4 (HE4) as a serum tumor biomarker in patients with ovarian carcinoma. Int J Gynecol Cancer. 21, 852-8. https://doi.org/10.1097/IGC.0b013e31821a3726
  12. Aziz MF (2009). Gynecological cancer in Indonesia. J Gynecol Oncol. 20, 8-10. https://doi.org/10.3802/jgo.2009.20.1.8
  13. Bian J, Li B, Kou X-J, Liu T-Z, Ming L (2013). Clinical significance of combined detection of serum tumor markers in diagnosis of patients with ovarian cancer. Asian Pac J Cancer Prev, 13, 6241-43. https://doi.org/10.7314/APJCP.2013.14.11.6241
  14. Boyle P, Levin B (2008). World Cancer Report. In: WHO, editor. Switzerland: International Agency for Research on Cancer.
  15. Chan KK, Chen CA, Nam JH, et al (2013). The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass. Gynecol Oncol, 128, 239-44. https://doi.org/10.1016/j.ygyno.2012.09.034
  16. Havrilesky LJ, Whitehead CM, Rubatt JM, et al (2008). Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 110, 374-82. https://doi.org/10.1016/j.ygyno.2008.04.041
  17. Hennessy BT, Coleman RL, Markman M(2009). Ovarian cancer. Lancet. 374, 1371-82. https://doi.org/10.1016/S0140-6736(09)61338-6
  18. Holcomb K, Vucetic Z, Miller MC, Knapp RC (2011). Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol. 205, 1-6. https://doi.org/10.1016/j.ajog.2011.05.029
  19. Huhtinen K, Suvitie P, Hiissa J, et al (2009). Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer, 100, 1315-9. https://doi.org/10.1038/sj.bjc.6605011

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