HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients

Abbink, Karin; Zusterzeel, Petra L.M.; Geurts-Moespot, Anneke; Herwaarden, Antonius E. van; Pijnenborg, Johanna M.A.; Sweep, Fred C.G.J.; Massuger, Leon F.A.G.

doi:10.1177/1010428318757103

Cited by 48 publications

(84 citation statements)

References 41 publications

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“…There is no specific blood protein biomarker that is recommended for use following an EC diagnosis; instead, regular clinical examination is advised with imaging. The ovarian cancer markers CA125 and HE4 have been shown to significantly correlate with prognosis; however, their detection rates in metastatic disease are low-54% and 75% respectively-and even lower with local recurrence: 39% and 16% [5]. Hence, more effective biomarkers are required that can detect EC recurrence and disease progression earlier, as well as reliably reflecting the underlying kinetics of the disease.…”

Section: Introductionmentioning

confidence: 99%

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression

Moss

Gorsia

Collins

et al. 2020

Cancers

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Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.

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Section: Introductionmentioning

confidence: 99%

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression

Moss

Gorsia

Collins

et al. 2020

Cancers

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“…In addition, Abbink et al . [15] reported the usefulness of HE4 protein concentration assay in detecting distant metastatic foci in cases of endometrial cancer, when its concentration is significantly higher than during local recurrence. In this function it performs significantly better than CA125, which was found elevated only in 37% of patients, compared to 67% for HE4.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of HE4 protein in differentiation of pelvic masses in woman

Brenk

Bodzek

Baliś

et al. 2019

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Introduction: HE4 protein (human epididymis protein-4), which is the fourth subfraction of human epithelial protein, is a glycoprotein widely used as a tumor marker in ovarian cancer. If was first discovered in the epididymal epithelium and recognized as a protease inhibitor contributing to sperm maturation. The plasma HE4 concentration may also be increased in gynecological pathologies other than ovarian cancer. Material and methods: The study was conducted between 2016 and 2017 among patients hospitalized in the Academic Department of Gynaecology. A total of 191 women were examined. Depending on the type of pathology which was the reason for hospitalization, 4 groups of patients were identified in the study. The first of these included 30 patients with ovarian cancer, the second 33 patients with benign ovarian lesion, the third 50 patients with endometrial cancer, and the fourth 28 patients with leiomyomas. Results: The highest concentration of HE4 protein was found in women with ovarian cancer, and it was statistically significantly higher compared to all other groups. Lower HE4 protein concentration than in women with ovarian cancer was reported in women with endometrial cancer, but it was statistically significantly higher compared to patients with uterine fibroids. Conclusions: This marker may have significant clinical value in the differentiation of benign ovarian pathology from ovarian cancer. The study confirms the validity of using HE4 results in the assessment of potential malignancy of ovarian and endometrial lesions.

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“…By contrast, studies reporting significant differences in HE4 values when analyzing other prognostic factors, such as deep myometrial invasion, did not find this correlation when studying lymphatic involvement . One study suggested that the discrepancy in correlation with lymph node metastasis might be due to the small number of cases .…”

Section: Summary Of Findingsmentioning

confidence: 95%

“…Existing evidence on the application of HE4 to detect lymphatic metastases is conflicting. Some studies have found no significant difference between preoperative HE4 level and lymphatic metastasis, whereas others have reported a significant rise in preoperative HE4 if lymphatic involvement is present …”

Section: Summary Of Findingsmentioning

confidence: 96%

HE4 tumor marker as a predictive factor for lymphatic metastasis in endometrial cancer

Romera

Cuesta-Guardiola

Vielba

et al. 2020

Intl J Gynecology & Obste

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Endometrial cancer is the most common genital cancer in high-resource countries.Treatment is essentially surgical, but the role of lymphadenectomy in the treatment of low-stage and low-grade tumors has not been defined. Although no tumor factors have been validated for use as preoperative prognostic markers of endometrial cancer at yet, human epididymis protein 4 (HE4) has received much interest as a potential diagnostic and prognostic tumor marker. Since 2008, several studies have explored its utility in the management of endometrial cancer: HE4 may be a useful preoperative prognostic marker because it is associated with lymphatic metastasis and other unfavorable factors in endometrial cancer. In addition, some studies have explored a HE4 cutoff value to classify patients according to lymph node involvement. HE4 might be beneficial as a serum marker that helps clinicians in the decision-making algorithm for treatment of endometrial cancer, enabling them to perform individualized operations and decrease the adverse effects of unnecessary surgery. K E Y W O R D SEndometrial cancer; HE4; Human epididymis protein 4; Lymphadenectomy; Lymphatic metastasis; Preoperative procedure; Prognosis; Tumor marker

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HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients

Abstract: Elevated serum HE4 is an independent risk factor for reduced disease-free survival and overall survival. HE4 seems to be superior to CA125 in the detection of recurrent disease during follow-up, mainly in high-risk endometrial cancer patients who are more prone to distant metastasis.

Cited by 48 publications

References 41 publications

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression

Usefulness of HE4 protein in differentiation of pelvic masses in woman

HE4 tumor marker as a predictive factor for lymphatic metastasis in endometrial cancer

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