Huhtinen, K., et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br. J. Cancer 100, 1315-1319

Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
British Journal of Cancer (Impact Factor: 4.84). 03/2009; 100(8):1315-9. DOI: 10.1038/sj.bjc.6605011
Source: PubMed


Human epididymal secretory protein E4 (HE4, also known as WAP four-disulphide core domain protein 2) is a new promising biomarker for ovarian cancer but its specificity against ovarian endometriotic cysts is only superficially known. We, thus, analysed serum HE4 concentrations together with a tumour marker CA125 in serum samples of women diagnosed with various types of endometriosis, endometrial cancer or ovarian cancer, and in samples from healthy controls. The mean serum concentration of HE4 was significantly higher in serum samples of patients with both endometrial (99.2 pM, P<0.001) and ovarian (1125.4 pM, P<0.001) cancer but not with ovarian endometriomas (46.0 pM) or other types of endometriosis (45.5 pM) as compared with healthy controls (40.5 pM). The serum CA125 concentrations were elevated in patients with ovarian cancer, advanced endometriosis with peritoneal or deep lesions, or ovarian endometriomas, but not in the patients with endometrial cancer. The microarray results revealed that the mRNA expression of the genes encoding HE4 and CA125 reflected the serum protein concentrations. Taken together, measuring both HE4 and CA125 serum concentrations increases the accuracy of ovarian cancer diagnosis and provides valuable information to discriminate ovarian tumours from ovarian endometriotic cysts.

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    • "U/ml in the second trimester or beyond (Goh et al., 2014). Human epididymis protein 4 (HE4) levels have been found to be significantly lower in pregnant women compared with their premenopausal counterparts and rarely increased in patients with ovarian endometriotic cysts (Huhtinen et al., 2009; Moore et al., 2012). Therefore, the role of a combined assessment of CA125 and HE4 for the differential diagnosis between benign and malignant adnexal tumors in pregnancy should be further elucidated in future investigations. "
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    ABSTRACT: BACKGROUND Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships.
    No preview · Article · Oct 2015 · Human Reproduction Update
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    • "In humans, HE4, SLPI and several other WAP members co-locate in 20q (Bouchard et al., 2006) a region frequently amplified in a variety of cancers (Van Dekken et al., 2001). HE4, a putative protease inhibitor containing two WAP (Whey Acid Protein) domains (Li et al., 2013) has been used widely for the early screening (Winstead, 2009; Scholler et al., 2006) and for differential diagnosis (Huhtinen et al., 2009; Montagnana et al., 2009) of ovarian cancer, as well as for monitoring disease recurrence (Anastasi et al., 2010) and progression (Kobel et al., 2008). Its role in tumorogenesis is investigated by forced over expression of HE4 that promoted several malignant phenotypes including cell proliferation, cell invasion capability, anchorage independent growth and increased tumor growth (Li et al., 2013). "
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    ABSTRACT: Human Epididymis protein 4 (HE4) has recently been shown to improve the sensitivity and specificity of Epithelial Ovarian Cancer (EOC) diagnosis but its function in cancer cells is not clear. We evaluated HE4 expression, RMI and CA125 serum level as diagnostic tools of primary ovarian cancer in Egyptian women. The HE4 gene expression was evaluated by real time PCR in ovarian cancer of 50 Egyptian women. Ovarian cancer tissues were studied for the detection of the gene expression of HE4 by Quantitative Real Time PCR (Q RT-PCR). Serum Human cancer antigen 125 (CA 125) was measured in the serum of all participants of the study using immune sorbent assay (ELISA). The HE4 showed significant difference among ovarian malignant tumors patients compared to the control subjects (p<0.01). The best cutoff value 0.053 at which HE4 sensitivity was 92% and specificity was 96%. There was a significance correlation between HE4, RMI and CA125 in all patients of the study (p≤0.01 for both). The mRNA expression of HE4 was significantly high versus the control group in early stages and low grades of the disease (p = 0.00, 0.01, respectively). As well as, there was Increased HE4 expression in the late stages of the disease suggesting that it may be associated with poor prognosis as well. The HE4 could be considered as a good prognostic marker for ovarian cancer that increases the sensitivity of the CA 125 to absolute value without affection of CA125 accuracy and its positive predictive value.
    Full-text · Article · Apr 2015 · International Journal of Cancer Research
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    • "HE4 (human epididymal secretory protein E4; WAP four-disulphide core domain protein 2) alone or in combination with CA125 [30,31], are the only two biomarkers US FDA approved for monitoring of disease recurrence or progression, but not for screening. Recently, there has been a resurgence of efforts to identify ovarian cancer biomarkers. "
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    ABSTRACT: Ovarian cancer is the most lethal gynecologic disease due to delayed diagnosis, and ascites production is a characteristic of patients in advanced stages. The aim of this study was to perform the proteomic analysis of ascitic fluids of Mexican patients with ovarian carcinoma, in order to detect proteins with a differential expression pattern in the continuing search to identify biomarkers for this disease. Samples were collected from 50 patients from the Instituto Nacional de Cancerologia of Mexico under informed consent and with approval of the bioethics and scientific committees. After elimination of abundant proteins (Albumin/IgGs) samples were processed for 2D electrophoresis and further protein identification by Mass Spectrometry (MALDI-TOF). Molecules of interest were followed by western blot and lectin binding assays, and their tissue location by histo-immunofluorescence and confocal analysis. An area with a differential expression pattern among samples was located in the 2D gels. Identified proteins were 6 alpha 1 isoforms and 1 alpha 2 isoform of Haptoglobin, and 2 isoforms of Transthyretin. While Transthyretin isoforms were constitutively expressed in all samples, clear differences in the expression pattern of Haptoglobin alpha isoforms were found. Moreover, increased levels of fucosylation of Haptoglobin alpha isoforms analyzed in 40 samples by Aleuria aurantia lectin binding by 1D overlay assay showed a positive correlation with advanced stages of the disease. Tissue detection of Haptoglobin and its fucosylated form, by histo-immunofluorescence in biopsies of ovarian cancer, also showed a correlation with ovarian cancer progression. Moreover, results show that fucosylated Haptoglobin is produced by tumor cells. Increased numbers of highly fucosylated Haptoglobin alpha isoforms in ascitic fluids and the presence of fucosylated Haptoglobin in tumor tissues of ovarian cancer Mexican patients associated with advanced stages of the disease, reinforce the potential of fucosylated Haptoglobin alpha isoforms to be characterized as biomarkers for disease progression.
    Full-text · Article · Feb 2014 · Journal of Ovarian Research
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