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

Miriam Lenhard, P Stieber, Petra Stieber, Linda Hertlein, Angela Kirschenhofer, Sophie Fürst, Doris Mayr, Dorothea Nagel, Karin Hofmann, Katja Krocker, Alexander Burges
Clinical chemistry and laboratory medicine · 2011 · vol. 49(12) , pp. 2081–8 · doi:10.1515/cclm.2011.709 · PMID:21923475 · W2001610212
article OA: closed CC0 ⤵ 3 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Human epididymis protein 4 (HE4) alone and combined with CA125 using ROMA improve adnexal mass diagnostic accuracy, particularly for early-stage ovarian cancer.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

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.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

CA-125 Antigen Epididymal Secretory Proteins Immunoassay Ovarian Neoplasms Adolescent Adult Aged Aged, 80 and over Area Under Curve Biomarkers, Tumor Biomarkers, Tumor CA-125 Antigen Diagnosis, Differential Epididymal Secretory Proteins Female Humans Middle Aged Ovarian Neoplasms Retrospective Studies Risk Factors

Citation neighborhood (sparse)

Too few in-corpus citations on either side for a chart; here are the lists.

Cites (2)

Cited by (3)

References (46)

Cited by (3)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:16:35.898691+00:00
unpaywall
last seen: 2026-06-02T02:00:03.124865+00:00
License: CC0 · commercial use OK