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      Expression of HE4 in Endometrial Cancer and Its Clinical Significance

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          Abstract

          The main aims of this study were to determine the expression of human epididymis protein 4 (HE4) in endometrial cancer and to explore the relationships between HE4 expression, clinicopathological parameters, and prognosis. Immunohistochemistry was used to detect HE4 expression in 102 cases of endometrial cancer, 30 cases of endometrial atypical hyperplasia, and 20 cases of normal endometrium. The positive expression rate of HE4 in endometrial carcinoma was 84.62%, significantly higher than 66.67% in atypical hyperplasia ( P < 0.05) and 15.00% in normal endometrium ( P < 0.0.01). With the exception of stage II, HE4 expression in endometrial cancer showed an increasing tendency with increased clinical stage ( P < 0.05). The positive expression rate of HE4 increased with a decrease in the degree of differentiation. A statistically significant difference was observed between the highly differentiated group and the poorly differentiated group ( P < 0.05). Mortality in endometrial cancer patients with high HE4 expression was significantly higher than that in patients with low HE4 expression ( P < 0.05). Endometrial cancer patients with high HE4 expression have a poor prognosis.

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          Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients

          E Bignotti, M Ragnoli, L Zanotti … (2011)
          Background: To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis. Methods: Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4–EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated. Results: Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort. Conclusion: We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.
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            Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas.

            B Karlan, B Schummer, David Baldwin … (1999)
            Comparative hybridization of cDNA arrays is a powerful tool for the measurement of differences in gene expression between two or more tissues. We optimized this technique and employed it to discover genes with potential for the diagnosis of ovarian cancer. This cancer is rarely identified in time for a good prognosis after diagnosis. An array of 21,500 unknown ovarian cDNAs was hybridized with labeled first-strand cDNA from 10 ovarian tumors and six normal tissues. One hundred and thirty-four clones are overexpressed in at least five of the 10 tumors. These cDNAs were sequenced and compared to public sequence databases. One of these, the gene HE4, was found to be expressed primarily in some ovarian cancers, and is thus a potential marker of ovarian carcinoma.
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              HE4 as a biomarker for ovarian and endometrial cancer management.

              Guo-Neng Lu, Shi-chen Jiang, Karl Podratz … (2009)
              Ovarian and endometrial cancer will be diagnosed in over 63,000 women in 2009, resulting in 22,000 deaths in the USA. Histologic screening, such as pap smears for detection of cervical cancer, is not feasible for these diseases given difficulty with access to the tissue. Thus, a serum- screening test using a biomarker or panel of biomarkers would be useful to aid in cancer diagnosis, detection of recurrence and as a means to monitor response to therapy. In this review, we focus on the human epididymis protein (HE)4 gene, which appears to have potential as a biomarker for both of these diseases. The structure and methods of detection of HE4 are discussed. Preliminary data show that HE4 may have more potential than cancer antigen 125 in discriminating benign from cancerous ovarian masses, and has the strongest correlation with endometrial cancer of all markers tested to date. Utilizing risk stratification, a panel of biomarkers including HE4 may ultimately be useful for detecting ovarian and endometrial cancer at an early stage in patients at high risk.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date (Print): 2015
                Publication date (Electronic): 11 October 2015
                Volume: 2015
                Electronic Location Identifier: 437468
                Affiliations
                Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
                Author notes

                Academic Editor: Xuanjun Zhang

                Article
                DOI: 10.1155/2015/437468
                PMC ID: 4619810
                PubMed ID: 26539494
                SO-VID: 407b7096-460c-4543-b59b-753f402c9dfd
                Copyright © Copyright © 2015 Xiao Li et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 11 December 2014
                Date accepted : 11 January 2015
                Categories
                Subject: Research Article

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