Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management

Abstract

BACKGROUND The aim of this work was to analyze the diagnostic and prognostic value of serum human epididymis protein 4 (HE4) and Risk for Ovarian Malignancy Algorithm (ROMA) in epithelial ovarian cancer (EOC). METHODS Preoperative serum samples of 419 women (140 healthy controls, 131 ovarian benign cysts, 34 endometriosis, 114 EOC) were tested for CA125 and HE4 using fully automated methods (Abbott ARCHITECT) and validated cut-off values. RESULTS For the discrimination of benign masses from EOC, in pre-menopausal women the sensitivity and specificity were 92.3% and 59.4% for CA125, 84.6% and 94.2% for HE4, and 84.6% and 81.2% for ROMA while in post-menopausal women the sensitivity and specificity were 94.3% and 82.3% for CA125, 78.2% and 99.0% for HE4, 93.1% and 84.4% for ROMA. In patients with EOC, elevated CA125, HE4 and ROMA levels were associated with advanced FIGO stage, sub-optimally debulking, ascites, positive cytology, lymph node involvement and advanced age (all p≤0.05). Elevated HE4 and ROMA (both p≤0.01), but not CA125 (p=0.0579), were associated with undifferentiated tumours. In multivariable analysis, elevated HE4 and ROMA (all p≤0.05) were independent prognostic factors for shorter overall survival, disease free survival and progression free survival. CONCLUSIONS and IMPACT This study underlines the high specificity of HE4 in discriminating endometriosis and ovarian benign cysts from EOC and the high sensitivity of CA125 in detecting EOC. We demonstrated HE4 and ROMA as independent prognostic factors. Multicenter studies are needed to draw firm conclusions about the applicability of HE4 and ROMA in clinical practice.

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

“…Our results are somewhat consistent with those of previous studies (Hellström et al, 2003;Moore et al, 2008;Huhtinen et al, 2009;Montagnana et al, 2009;Moore et al, 2009;Moore et al, 2010;Nolen et al, 2010;Bandiera et al, 2011;Molina et al, 2011;Park et al, 2011;Van Gorp et al, 2011;Karlsen et al, 2012;Park et al, 2012), which reported that serum CA125 and HE4 levels were significantly higher in ovarian cancer women than those in benign ovarian tumor women and in healthy women. In accordance with previous observations , our results showed that serum CA125 and HE4 levels were found to be related to FIGO stage with higher concentrations in late stages (stage III/IV) than in early stages (stage I/II).…”

“…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).…”

Expression of miR-146a in patients with ovarian cancer and its clinical significance

“…ROMA index, originally described by Moore et al (48), is an algorithm, which takes into consideration the level of HE4 and CA125 together with menopausal status in order to classify patients with adnexal mass into groups of high or low risk of ovarian cancer. In patients with ovarian cancer, increased ROMA values were associated with advanced FIGO stage, undifferentiated tumors, ascites and lymph node involvement, as well as shorter overall, disease-free and progression-free survival rates (49,50). In the present study, high CA125 serum levels and increased ROMA values (reflecting the advancement of ovarian cancer) correlated with low expression of miR-146a in primary tumor tissues.…”

Is the Risk of Ovarian Malignancy Algorithm Better Than Other Tests for Predicting Ovarian Malignancy in Women with Pelvic Masses?

“…In 2008, Moore et al [13] developed the risk of ovarian malignancy algorithm (ROMA), a dual biomarker (CA125 and HE4)-based test. ROMA gave better OC prediction with high sensitivity and specificity in several studies [14,15] . However, studies that compared these novel tests against CA125, RMI and US scores in Asian women were limited.…”