Serum HE4 as a prognostic marker in endometrial cancer — A population based study

Brennan, Donal J.; Hackethal, Andreas; Metcalf, Alex; Coward, Jermaine; Ferguson, Kaltin; Oehler, Martin K.; Quinn, Michael; Janda, Monika; Leung, Yee; Freemantle, Michael; Webb, Penelope M.; Spurdle, Amanda B.; Obermair, Andreas

doi:10.1016/j.ygyno.2013.10.036

Cited by 87 publications

(91 citation statements)

References 25 publications

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“…[10][11][12] Besides CA125, EC also could be diagnosed by elevated levels of HE4, CA724, and CA19-9, each with their own unique advantages. [13][14][15] In our test, we detected serum level of HE4, CA125, CA724, and CA19-9 in 105 patients with EC; the results showed that the level of tumor markers was obviously higher in the EC group than that in the healthy controls. Sensitivity of HE4 in patients with EC was 58%, much higher than sensitivity of CA125, CA724, and CA19-9 (35.4%, 11.3%, and 16.3%, respectively).…”

Section: Discussionmentioning

confidence: 74%

Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer

Bian

Sun

et al. 2016

Technol Cancer Res Treat

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Purpose: Serum markers with increased sensitivity and specificity for endometrial cancer are required. To date, no good marker has met this standard. The aims of our study were to evaluate the utility of tumor markers HE4, CA125, CA724, and CA19-9 as potential markers in patients diagnosed with endometrial cancer. Methods: Blood samples from 105 patients with endometrial cancer and 87 healthy women were analyzed by Roche electrochemiluminescent immunoassay, and serum values were measured for the following biomarkers: HE4, CA125, CA724, and CA19-9. Results: Serum HE4, CA125, CA724, and CA19-9 concentrations were significantly higher in patients with endometrial cancer, compared with controls (P < .001). In the receiver operating characteristic analysis, the area under the curve value for combination of HE4, CA125, CA724, and CA19-9 was 82.1% (95% confidence interval: 75.3%-86.2%), the maximum area of the test groups. For all stages of patients with endometrial cancer, HE4 had higher sensitivity (58%), positive predictive value (60%), and negative predictive value (67%) than any other single tumor marker, and in the combination of HE4, CA125, CA724, and CA19-9, the sensitivity and positive predictive values reached 59.1% and 88%, respectively. Meanwhile, the receiver operating characteristic area under the curve of the combination of the 4 markers was significantly increased than any other group, either in stage I or in stage II to IV cases. HE4 and CA125 both correlate with advanced age; in addition, HE4 was related to pathology subtypes and positive adnexal involvement, CA125 was related to International Federation of Gynecology and Obstetrics stage, CA19-9 was related to International Federation of Gynecology and Obstetrics stage, and CA724 was correlated with positive lymph node. Conclusion: Combination of HE4, CA125, CA724, and CA19-9 has the highest value in diagnosing endometrial cancer, and they can be a useful tissue immune marker for patients with endometrial cancer.

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Section: Discussionmentioning

confidence: 74%

Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer

Bian

Sun

et al. 2016

Technol Cancer Res Treat

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“…In a meta-analysis, Zhen et al reported that the diagnostic accuracy of HE4 in distinguishing ovarian cancer from other benign gynecological diseases was found to be superior to that of CA125 (23). More recently, Brennan et al reported in a large population-based study that serum HE4 may be a useful prognostic biomarker in endometrial cancer (17). Furthermore, Yang et al determined its importance as a preoperative predictor for optimal tumour cytoreductive surgery in epithelial ovarian cancer (18).…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies have reported its specifity and sensitivity as an ovarian cancer biomarker (16). In 2009, the United States Food and Drug Administration (FDA) approved HE4 as a useful marker for monitoring patients with epithelial ovarian cancer (17); and in September, 2011, the FDA also approved marketing of HE4 for the detection of ovarian masses (18). There is accumulating evidence that HE4 may also be a useful marker for endometrial cancer.…”

Section: Introductionmentioning

confidence: 99%

Serum human epididymis protein 4 levels in colorectal cancer patients

Kemal

Demirag

Bedir

et al. 2017

Molecular and Clinical Oncology

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Abstract. Tumour markers are widely used for the diagnosis, staging and monitoring of colorectal cancer (CRC) patients in clinical practice. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most frequently used biomarkers in CRC patients. A number of studies have recently investigated the presence of human epididymis protein 4 (HE4) overexpression in certain cancer types. Its significance in ovarian and endometrial cancer has been well-demonstrated. The aim of the present study was to evaluate the significance of serum HE4 levels in CRC patients. A total of 46 newly diagnosed CRC patients and 36 age-and gender-matched healthy subjects were included in the study. The concentrations of CEA and CA19-9 were also determined and compared according to HE4 levels. HE4 positivity was determined in 13 of the 46 cases (28.3%) in the CRC group, but no HE4-positive subjects were identified in the control group (0%; P=0.009). The area under the receiver operating characteristic curve for HE4 positivity was 0.641 (95% CI: 0.523-0.760). HE4 was statistically significantly positive in patients with stage III-IV disease and in those with high CA

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“…Brennan et al performed a large population-based cohort study to evaluate if serum HE4 can offer preliminary pre-operative risk stratification for EC. Specifically because of the high expression level of HE4 in EC tissue, and the increased serum level in this group of patients [28,29]. The result strongly implied that serum HE4 was an independent poor prognostic marker, and it was suggested to use HE4 serum assay as a cost-effective approach to avoid unnecessary lymphadenectomy in patients with low risk EC.…”

Section: Human Epididymis Protein 4 (He4)mentioning

confidence: 82%

“…In a different paper the expression of HE4 in EC and its relations to clinicopathological parameters and prognosis of EC was studied. The goal was to detect the expression rate of HE4, by means of immunohistochemical using streptavidin-peroxidase, in EC, endometrial atypical hyperplasia, and normal endometrial tissue samples, respectively [27,29]. The results implied that the intensity of HE4 expression increased with degree of malignancy.…”

Section: Human Epididymis Protein 4 (He4)mentioning

confidence: 99%

Biological markers with potential clinical value in endometrial cancer — review of the literature

et al. 2017

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Endometrial carcinoma (EC) is the most common malignancy of the female genital tract encountered in western countries, making it the fourth most common cancer in women. The incidence of uterine cancer is on the rise throughout the developed world where diagnosis is increasingly observed among younger patients. With regard to this, attention has been focused on conducting more studies to achieve a better understanding of the molecular genetics related to endometrial carcinogenesis. Over the years, EC has been classified into two broad histopathological subtypes based on the mechanism of development, and we can therefore observe specific biomarkers related to the respective subtype. Based on this idea, more research has been carried out in the last decade, using biotechnological methods, with the aim to identify new potential tumor markers. By translating these findings into clinical use one may facilitate accurate diagnosis and prognostic prediction, and contribute to individualized treatment. Without a doubt, there is a demanding need to identify biomarkers that can be adopted in clinical practice in order to reduce the time needed to obtain diagnosis. Such markers may be of great value in improving patient outcome. However, a number of problems remain to be solved before this becomes a reality. This paper briefly reviews the current status of rising biomarkers in EC.

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Serum HE4 as a prognostic marker in endometrial cancer — A population based study

Cited by 87 publications

References 25 publications

Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer

Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer

Serum human epididymis protein 4 levels in colorectal cancer patients

Biological markers with potential clinical value in endometrial cancer — review of the literature

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