Evaluation of human epididymis protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA) as diagnostic tools of type I and type II epithelial ovarian cancer in Japanese women

Abstract

Human epididymis protein 4 (HE4) levels and the Risk of Ovarian Malignancy Algorithm (ROMA) have recently been shown to improve the sensitivity and specificity of epithelial ovarian cancer (EOC) diagnosis. We evaluated HE4 levels and ROMA as diagnostic tools of type I and type II EOC in Japanese women. Women who had a pelvic mass on imaging and were scheduled to undergo surgery were enrolled as ovarian mass patients. Serum levels of carbohydrate antigen 125 (CA125) and HE4 were tested in 319 women (131 benign, 19 borderline, 75 malignant, and 94 healthy controls). CA125, HE4, and ROMA were evaluated for sensitivity and by receiver operating characteristics (ROC) in type I and type II EOC. The results showed that, at 75 % specificity, the sensitivity of CA125 and HE4 for type II was 92.1 % for both markers and for type I was 51.5 % and 78.8 %, respectively. The sensitivities of ROMA (type I, 84.8 % and type II, 97.4 %) were better than those of CA125 and HE4. CA125, HE4, and ROMA were all highly accurate markers for type II. For type I, HE4 and ROMA showed better sensitivity than CA125. ROMA displayed the best diagnostic power for type I and type II including for the early stage of type I. In conclusion, HE4, CA125, and ROMA are valuable markers for type II EOC diagnosis. HE4 and ROMA analyses may improve differentiation between type I EOC and a benign mass. Measurement of combined HE4 and CA125 levels provides a more accurate method for EOC diagnosis.

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

“…Several reports have demonstrated that ROMA had a better diagnostic performance than either marker alone (Moore et al, 2008;Moore et al, 2009;Bandiera et al, 2011;Molina et al, 2011;Moore et al, 2011;Ortiz-Muñoz et al, 2014;Fujiwara et al, 2015). These findings appear to be in line with those of Li et al, (Li et al, 2012) who conducted a meta-analysis to clarify conflicting results existing in the diagnostic performance comparison among ROMA, HE4 and CA125.…”

“…Although several studies have reported that ROMA yielded a better diagnostic accuracy than either marker alone (Moore et al, 2008;Moore et al, 2009;Bandiera et al, 2011;Molina et al, 2011;Moore et al, 2011;Li et al, 2012;Ortiz-Muñoz et al, 2014;Fujiwara et al, 2015), other studies failed to demonstrate its superiority over CA125 or HE4 alone for assessing the risk of ovarian cancer (Montagnana et al, 2011;Van Gorp et al, 2011;Wang et al, 2014).…”

Human Epididymis Protein 4 (HE4) mRNA as a Prognostic Marker in Ovarian Tumors in Relation to RMI and CA125

“…In the present study, the CA 125 showed the same sensitivity of HE4 (92%), this result is consistent with the study by Karlsen et al (2012) However, this shows consistency with previous studies, as the study by Fujiwara et al (2015), who found that the AUCs for HE4 were better than the AUC for CA 125 in distinguishing between benign diseases and EOC, the study by Hamed et al (2013) AUC values were (0.96) for HE4 and (0.82) for (CA 125), the study by Karlsen et al (2012) AUC was highest for RMI (0.905) followed by HE4 (0.864) and CA125 (0.854), respectively and for the Montagnana et al (2009) study, AUC for HE4 is higher than CA 125. There was a highly significance (r = 0.746, p<0.001) correlation between levels of CA 125 and tissue HE4 measured by real time PCR in all groups of the study.…”

“…This result is consistent with the study by Macedo et al (2014) which found that HE4 level is a useful preoperative test for predicting the benign or malignant nature of pelvic masses, Karlsen et al (2012) which found a prominent up-regulation of HE4 expression was seen in epithelial ovarian cancer tissue, especially in serous and endometrioid adenocarcinoma. No expression wasdetected in normal ovarian tissue and a lower expressionwas observed in both benign and borderline ovariantumors compared with protein expression levels in epithelial ovarian cancer, Fujiwara et al (2015) which found the median serum levels of CA 125 and HE4 were significantly higher in patients with type I and type II EOC than in patients with benign diseases 181 Int. J.…”

“…This suggests the possibility of usage this gene as an early diagnostic marker in ovarian cancer which is a novel finding in this study. As the study done by Fujiwara et al (2015) compared between results of 2 types in cancer group only, type 1 and 2 (low and high grades) EOC.…”