Human epididymis protein 4 as a serum marker for diagnosis of endometrial carcinoma and prediction of clinical outcome

Zanotti, Laura; Bignotti, Eliana; Calza, Stefano; Bandiera, Elisabetta; Ruggeri, Giuseppina; Galli, Claudio; Tognon, Germana; Ragnoli, Monica; Romani, Chiara; Tassi, Renata; Caimi, Luigi; Odicino, Franco; Sartori, Enrico; Pecorelli, Sërgio; Ravaggi, Antonella

doi:10.1515/cclm-2011-0757

Cited by 73 publications

(70 citation statements)

References 27 publications

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“…The number of patients with histological grading G1, G2, and G3 was 34 (73.9%), 9 (19.5%), and 3 (6.5%), respectively. Serum HE4 levels in these groups of patients were 91.70 ,120, and 213 pmol/L, respectively, while CA125 levels were 16 A total of 33 (94.29%) patients were diagnosed with other pathologies, including 17 (48.57%) women with endometrial polyps, 2 (5.71%) with hyperplasia without atypia, and 14 (40.00%) with both, endometrial polyp and hyperplasia without atypia. The statistical significance of the S-W test was < 0.001 for both tumor markers.…”

Section: Resultsmentioning

confidence: 87%

“…HE4, along with CA125 and the menopausal status, is used to determine the risk of malignancy through an algorithm in patients with adnexal tumors [15]. Recent studies have shown that HE4 levels are elevated in patients with EC [11,16,17]. The role of tumor markers in detecting early stages of EC may be limited since postmenopausal bleeding is an early symptom of the disease [18].…”

Section: Discussionmentioning

confidence: 99%

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The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies

et al. 2016

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Objectives: The aim of the study was to assess the role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies. Material and methods:A retrospective study of 87 patients with endometrial pathologies was conducted. Tumor markers were assessed two weeks before surgical intervention in each subject. The final diagnosis was established on the basis of the histopathological examination of the endometrium.Results: Serum HE4 levels were significantly higher in patients with endometrial cancer (EC) as compared to non-malignant endometrial pathologies (p < 0.001), patients with stage I EC as compared to non-malignant endometrial pathologies (p < 0.001), and patients with stage Ia EC as compared to non-malignant endometrial pathologies (p = 0.003). Serum CA125 levels were not significantly different as far as these groups of patients were concerned. Both tumor markers were significantly higher in patients with stage II-III as compared to stage I EC and non-malignant endometrial pathologies (p < 0.001 for both markers). Sensitivity and specificity of HE4 at the cut-off level of 70 pmol/L for detecting endometrial malignancies were 73.08% and 85.71%, respectively. Sensitivity and specificity of CA125 at the cut-off level of 35 U/mL were 29.41% and 94.29%, respectively. The area under the curve (AUC) for HE4 was 0.875, suggesting that this marker reliably differentiates malignant from non-malignant endometrial pathologies (p < 0.001). AUC for CA125 was 0.552, suggesting that this marker does not reliably differentiate between malignant and non-malignant endometrial pathologies (p = 0.414).Conclusion: HE4, in contrast to CA125, might be a useful tool for detecting malignant endometrial pathologies.

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies

et al. 2016

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“…Two studies without a clear documentation of cutoff values reported the same specificity of 90%, while the sensitivities are 95% and 98%, respectively [21,22]. Other three studies using 50-70 pM cutoff values reported 78.8% sensitivity and 100% specificity [23][24][25].…”

Section: Introductionmentioning

confidence: 92%

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Duan

et al. 2016

Expert Review of Molecular Diagnostics

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“…HE4 has been reported to be upregulated in several types of cancers including those of the ovary (16), endometrium (17), lung (18,19), breast (7,15), stomach and pancreas (20). The expression of HE4 in ovarian cancer was initially reported in 1999 (16), and it was subsequently cleared as a new biological marker of ovarian cancer in 2003 (21).…”

Section: Introductionmentioning

confidence: 99%

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

et al. 2014

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Abstract. Available evidence on the proliferation-promoting effect of HE4 remains controversial, and few studies have been carried out on the molecular mechanism of chemoresistance mediated by HE4. The aim of the present study was to investigate the influence of exogenous recombinant HE4 protein on proliferation and resistance to carboplatin in ovarian cancer cells. The human ovarian cancer cell line (SKOV-3) was exposed to recombinant HE4 protein (0-1 µg/ml) for different durations based on the schemes. Cell viability was evaluated by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Markers of apoptosis (Bax and Bcl-2) were assessed by western blotting. Furthermore, Affymetrix microarray analysis was performed to investigate transcriptome profiling. The differential expression of four genes was verified by quantitative real-time PCR. The HE4 protein enhanced cell viability, promoted accumulation of cells in the G2/M phase and attenuated carboplatin-induced apoptosis. HE4 markedly decreased the Bax/Bcl-2 ratio. Candidate genes (387) (236 upregulated and 151 downregulated) were obtained by microarray analysis. Among those upregulated, several Gene Ontology (GO) terms related to cell cycle regulation and proliferation were significantly overrepresented and those within the downregulated dataset included genes involved in several aspects of the DNA damage response such as positive regulation of apoptosis. No information concerning the EGFR-MAPK pathways in a recent report on HE4 was acquired. The mRNA expression of the candidate genes determined by quantitative real-time PCR was significantly correlated with the microarray data. The present study indicates that the HE4 protein plays a promotive role in the proliferation and resistance to carboplatin in ovarian cancer cells, implicating the value of HE4 to predict tumor growth potential and resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC).

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Human epididymis protein 4 as a serum marker for diagnosis of endometrial carcinoma and prediction of clinical outcome

Cited by 73 publications

References 27 publications

The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies

The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells

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