The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses.

ABSTRACT

BACKGROUND: Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) improves diagnostic accuracy. METHODS: We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma n=78, leimyoma n=66, endometriosis n=52, functional ovarian cysts n=79, other n=10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage I 22, II 15, III 78, IV 10). CA125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally. RESULTS: The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA125 alone was not significantly different to HE4 alone in premenopausal (CA125 86.7, HE4(a) 82.6, HE4(e) 81.6% p>0.05) but significantly different in postmenopausal [CA125 93.4 vs. HE4(a) 88.3 p=0.023 and vs. HE4(e) 87.8% p=0.012] patients. For stage I OC, HE4 as a single marker was superior to CA125, which was the best single marker in stage II-IV. The combination of CA125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses [CA125 70.9, HE4(a) 67.4, HE4(e) 66.0, ROMA(a) 76.6 and ROMA(e) 74.5%], especially in stage I OC [CA125 27.3, HE4(a) 40.9, HE4(e) 40.9, ROMA(a) 45.5 and ROMA(e) 45.5%]. CONCLUSIONS: CA125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC.