The role of human epididymis secretory protein E4 in patients with endometrial cancer and premalignant endometrial lesions

Yılmaz, Setenay Arzu; Altınkaya, Sündüz Özlem; Kerimoğlu, Özlem Seçilmiş; Pekin, Aybike Tazegül; Akyürek, Fıkret; İlhan, Tolgay Tuyan; Benzer, Nilgün; Ünlü, Ali; Yüksel, Hasan; Çelık, Çetin

doi:10.3109/01443615.2016.1174199

Cited by 11 publications

(14 citation statements)

References 24 publications

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“…These reports are in line with our results including the HE4 levels being higher in patients with the involvement of lymphatic and blood vessels and in patients with tumor metastases into the lymph nodes. Yilmaz et al and Kemik et al confirmed that in endometrial cancer patients, HE4 marker may be used for individual treatment planning 21,22…”

Section: Discussionmentioning

confidence: 96%

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

Cymbaluk‐Płoska¹,

Chudecka‐Głaz²,

Pius-Sadowska

et al. 2017

OTT

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IntroductionEndometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.AimTo explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methodsIncluded in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA). MMP2 concentrations were quantified in the serum using multiplex immunoassays.ResultsWe observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003). The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV) vs low (FIGO I and II) clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3) on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre-menopausal patients and 84% vs 79% in post-menopausal patients.ConclusionHE4 and MMP2 are characterized by high specificity and may be useful as biomarkers in the diagnostics of endometrial cancer. When determined preoperatively, HE4 is correlated with the prognostic factors of endometrial cancer and may be helpful in the planning of individual treatment of endometrial cancer patients.

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Section: Discussionmentioning

confidence: 96%

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

Cymbaluk‐Płoska¹,

Chudecka‐Głaz²,

Pius-Sadowska

et al. 2017

OTT

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“…In the study by Yilmaz et al [ 15 ], a correlation was found between HE4 levels and disease severity. A link was found between HE4 levels and FIGO stage (RR = 0.482, p < 0.001), between endometrial thickness and HE4 levels, between lymph node invasion and HE4 levels (RR = 0.387; p < 0.001) and with tumor size (RR = 0.386, p < 0.001).…”

Section: Discussionmentioning

confidence: 98%

“…However, the HE4 marker can be increased in other benign situations such as age, smoking, renal failure, tubo-ovarian abscesses, or malignant in pancreatic adenocarcinoma, borderline ovarian tumors. We therefore try to take these confounding factors into account in order to better evaluate and interpret the variations of the HE4 marker [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study

et al. 2021

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Background: Endometrial cancer is the most common pelvic gynecological cancer in France. The most frequent symptom is post-menopausal bleeding and is one of the primary reasons for consultation in gynecological emergencies. The treatment is very codified and consists of a surgical intervention for anatomopathological analysis. The latter is frequently reassuring. These interventions are often performed in mild situations and there is currently no element to be sufficiently reassuring to avoid surgery. This study aims to explore the sensitivity of an innovative marker: Human Epididymis 4 (HE4) in the diagnosis approach of endometrial cancer in case of postmenopausal bleedings. Methods: This is a prospective multicenter diagnostic study with three centers involved. Inclusion criteria are any patient with post-menopausal bleeding who is to undergo hysteroscopy, endometrial biopsy, or endometrial resection. In accordance with the recommendations for the management of post-menopausal bleedings, the medical conduct consists of performing a clinical examination, an ultrasound and, in general, even in case of paraclinical examination reassuring, an anatomopathological analysis. This pathological analysis can be obtained in several ways: biopsy, hysteroscopy-curettage (which is the most frequently performed surgery), and hysterectomy. Our protocol consists of taking a blood sample from each woman who will undergo one of the interventions mentioned above. The dosage of HE4 and CA125 requires the withdrawal of an additional heparinized tube during the preoperative assessment usually performed. This research is therefore classified as non-interventional. The primary outcome is to evaluate the sensitivity of the HE4 marker in patients with postmenopausal bleeding in the diagnosis of endometrial cancer. The secondary outcomes are other parameters (specificity, VPP, VPN) of HE4, Evaluating the diagnostic capabilities of the CA125 marker alone and associated with HE4, as well as those of the REM and REM-B algorithms. We aim to include 100 patients over a period of one year in three centers. Discussion: As of now, there is no biological marker used in routine practice in the diagnosis of endometrial cancer. The ultimate goal of HE4 in endometrial cancer is to avoid surgery for those who are identified as non-sick. This study is the precursor of others for use in routine practice, HE4 would represent a great help to diagnosis if our study demonstrates it as reliable in the management of these patients and avoid many unnecessary and risky surgeries.

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“…Localized EC treatment consists of hysterectomy and double adnexectomy. Moreover, the identification of those patients that should undergo a pelvic and/or para-aortic lymphadenectomy depends on several parameters ( 16 , 17 , 18 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of endometrial carcinoma with tumor markers HE4 and CA125 in serum and endometrial tissue samples

Cuesta-Guardiola

Carretero

Martinez-Martinez

et al. 2021

J Turkish German Gynecol Assoc

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Objective: Diagnosis of endometrial cancer (EC) is made by biopsy sampling with pathological analysis, but it is extremely important to make an accurate diagnosis in order to plan the specific treatment. We hypothesized that human epididymis protein 4 (HE4) in endometrial tissue and in serum could be beneficial for a more precise diagnosis. Material and Methods: This prospective study compared patients with EC against non- EC, matched through several variables. The inclusion criteria were: females older than 18 years who accepted to participate; who had never undergone surgery for other oncological pathologies (ovarian, colon, cervical carcinoma or uterine sarcoma); none of them had received preoperative chemo- or radio-therapy; and no participant had any severe renal or liver pathology. All had pre-surgery blood sampling and then underwent hysterectomy. Histopathological assessment of endometrial samples was made by a pathologist who compared normal histopathological staining with HE4-antibody staining. Results: In total there were 34 cases and 35 controls recruited. There was poor correlation between tissue HE4 in patients with and without carcinoma. However, serum HE4 was significant for the diagnosis of endometrial carcinoma (median EC: 123.1 U, median NE: 64.67 U, p=0.002), although the carbohydrate antigen 125 level was not significant (p=0.208). Conclusion: The findings concerning the utility of HE4 contrast with earlier reports. However, the conclusions for serum measurements are positive and suggest that the tumor marker HE4 seems to be able to diagnose EC.

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The role of human epididymis secretory protein E4 in patients with endometrial cancer and premalignant endometrial lesions

Cited by 11 publications

References 24 publications

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study

Identification and characterization of endometrial carcinoma with tumor markers HE4 and CA125 in serum and endometrial tissue samples

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