Serum HE4 Concentrations Research Articles

Evaluation of He4 Use in the Diagnosis of Ovarian Cancer: First and Second Recurrence, and an Analysis of HE4 Concentration during Second- and Third-Line Chemotherapy.

HE4 is a commonly used tumor marker for ovarian cancer (OC) diagnosis. In our study, we aimed to assess its use in the diagnosis of subsequent OC recurrences and to evaluate its changes during recurrence diagnosis and the subsequent lines of chemotherapy treatment. This retrospective single center study was conducted on 188 patients treated for ovarian cancer recurrence at the Department of Gynecological Surgery and Gynecological Oncology. The sensitivity and specificity of HE4 for patient survival prediction were analyzed using Receiver Operating Characteristics (ROC) and area under the curve (AUC) with 95% confidence intervals (95% CI). Survival times to reach one of the endpoints (OS, PFS, TFI, PFS2, TFI2) were analyzed using Kaplan-Meier curves. Elevated HE4 levels at the time of first relapse diagnosis, and after the third and the last course of second-line chemotherapy, significantly influences the time from OC diagnosis until first disease recurrence (PFS2) (p = 0.005, p = 0.015 and p = 0.002, respectively). Additionally, elevated serum HE4 concentration at the time of OC diagnosis (p = 0.012), and its later recurrence (first (p < 0.001), and second recurrent diagnosis (p = 0.143)) significantly influences patient OS. Increased HE4 concentration at the end of chemotherapeutic treatment negatively affects overall patient survival ((p = 0.006 for second line chemotherapy and (p = 0.022) for elevated HE4 concentration after the last course of third-line chemotherapy). Our preliminary results show an encouraging diagnostic and prognostic role of HE4 in recurrent ovarian cancer. HE4 measurements at different treatment time points during the second- and third-line chemotherapy treatment seem to correlate with patient survival.

HE4 is associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients.

To explore whether HE4 was associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients. Ninety-six primary fallopian tube carcinoma (PFTC) patients from March 2011 to June 2019 were enrolled in this study. Serum CA125 and HE4 concentrations were measured at four time points including primary diagnosis, postsurgery, pre-recurrence, and recurrence. The relations between clinical risk prognostic factors with HE4 concentrations were investigated, and multivariate survival analysis was used to calculate the hazard ratios between HE4 levels with recurrence-free survival and overall survival. HE4 were significantly elevated in poor performance status, advanced stage, high histological grade and residual tumor diameter >1 cm, and positive lymph node status, respectively, compared with those in well performance status, early stage, low histological grade, residual tumor diameter ≤1 cm, and negative lymph node status, respectively. Multivariate survival analysis indicated serum HE4 can predict outcome of recurrence-free survival and overall survival with hazard ratios of 9.92 (95% confidence interval [CI]: 2.95-33.32) and 3.12 (95% CI: 1.07-9.08), respectively. HE4 is associated with clinical risk prognostic factors in PFTC and contributes to predict survival outcome in PFTC cases.

Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

Evaluation of Serum Human Epididymis Secretory Protein 4 (HE4) in Benign Endometrial Disease and Endometrial Cancer

Abstract Objective The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women are being observed. More than 80% of cases are diagnosed in early stages due to early symptoms like abnormal bleeding. Aim of our study to evaluate the ability of serum HE4 concentration to differentiate between benign endometrial disease and endometrial cancer and ass’s correlation it with prognosis of EC. Material and methods Serum HE4 level was measured in 85 patients with abnormal uterine bleeding. Based on histology after curettage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test Results The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 62 pmol/l. There was a significant difference between Stage (I – II) endometrial cancer, and Stage (III – IV) p = 0.01, Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). Conclusion HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic lymphadenectomy.

Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis

BackgroundHuman epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). MethodsSerum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. ResultsSerum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8–90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3–64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1–42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574–0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What’s more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = −0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). ConclusionsElevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB.

Diagnostic and prognostic value of HE4 in female patients with primary peritoneal carcinoma.

HE4 is a useful tumor marker for the diagnosis of ovarian, endometrial, and fallopian tube carcinoma. The aim of our study was to investigate the value of serum HE4 compared with CA125 in the diagnosis of primary peritoneal carcinoma and the estimation of treatment response and recurrence. Serum HE4 and CA125 concentrations were measured in both primary peritoneal carcinoma patients and benign gynecological disease controls. The treatment response and recurrence were assessed by serum HE4 and CA125 levels in primary peritoneal carcinoma patients. Serum HE4 and CA125 levels were significantly increased in primary peritoneal carcinoma patients compared with benign disease controls ( P<0.001). Compared with CA125, HE4 had lower sensitivity (84.2% vs. 94.7%), but higher specificity (99.2% vs. 85.3%); the combination of HE4 and CA125 led to higher sensitivity and specificity. In the receiver operating characteristic analysis, the area under the curve was 0.956 for HE4, for CA125 was 0.953, for HE4+CA125 was 0.979. Furthermore, HE4 and CA125 were closely associated with treatment response, and our results indicated that primary peritoneal carcinoma patients displayed a larger drop of HE4 compared with CA125 (75.8% vs. 61.5%). Combined with CA125, HE4 elevation better predicted recurrence in primary peritoneal carcinoma patients during the remission period after treatment. This study indicated that the detection of serum HE4 changes may enhance the effectiveness for detecting primary peritoneal carcinoma and estimating the outcome of treatment and recurrence in female primary peritoneal carcinoma patients.

Human epididymis protein 4 concentration is not associated with liver fibrosis and cirrhosis in a case control study

BackgroundHuman epididymis protein 4 (HE4) is an emerging fibrotic biomarker which has been studied in chronic kidney disease cohorts. However, it is unclear if the serum level of HE4 may be altered in patients with liver fibrosis and cirrhosis. Methodswe assessed serum HE4 concentrations in patients (n = 366) with chronic liver diseases (CLD) and compared to matched healthy controls (n = 366). Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) was also performed on all patients. Liver biopsy was performed on 34 of 366 subjects. Moreover, we analysed a subgroup of patients with confirmed cirrhosis to validate the correlation between HE4 and the severity of cirrhosis. Child-Pugh (CP) score was evaluated in this subgroup. ResultsNo statistically significant differences were observed in the median HE4 level between patients with fibrosis and cirrhosis and controls (median: 56.2 vs. 55 pmol/L, p = .562). Neither were any significant differences found among different groups with Child-Pugh Classes A, B and C (median: 56.9, 58.3 and 52.1 pmol/L, respectively; p = .842). Correlation analysis did not show a significant correlation between HE4 and degree of liver fibrosis according to LSM values or histological assessment (r = 0.159, p = .239; r = 0.045, p = .788). ConclusionsSerum HE4 level does not appear to be associated with fibrotic and cirrhotic liver, suggesting that HE4 may not serve as a valuable clinical biomarker for liver fibrosis and cirrhosis.

Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients

BackgroundRenal fibrosis remains an important cause of kidney allograft failure. The objective of this study was to evaluate the performance of serum human epididymis secretory protein 4 (HE4) as a biomarker for renal fibrosis in kidney transplant recipients. MethodsA total of 103 kidney transplantation patients were enrolled in this study, and serum HE4 concentrations were detected using the chemiluminescent microparticle immunoassay. Renal biopsy was carried out, and histological findings were assessed by immunohistochemistry. ResultsMedian serum HE4 concentrations were significantly increased in kidney transplant recipients (186.2 pmol/l, interquartile range [IQR] 125.6–300.2) compared with control subjects (34.3 pmol/l, IQR 30.4–42.3, p < 0.0001). Meanwhile, serum HE4 concentrations were significantly increased along with disease severity (p < 0.0001). In addition, we found serum HE4 concentrations to be strongly correlated with the severity of fibrosis (IF/TA 0, 1, 2, and 3: 114.3, 179.0, 197.8, and 467.8 pmol/l, respectively; p < 0.0001) and serum HE4 concentrations significantly correlated with HE4 tissue expression concentrations in renal biopsy. ConclusionsSerum HE4 was increased in kidney transplant recipients with decreased kidney function and renal fibrosis and was correlated with the severity of the disease, suggesting that HE4 has the potential to be used as a novel clinical biomarker for evaluating kidney function and predicting renal fibrosis in kidney transplant recipients.

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

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.

Serum HE4 is correlated to prognostic factors and survival in patients with endometrial cancer.

The extent of surgery and the decision for adjuvant treatment in patients with endometrial cancer (EC) depend on the presence of risk factors for lymph node metastases and disease recurrence. Postoperative markers such as myometrial infiltration and specific mutations can select patients for adjuvant treatment but will not influence surgical planning. A biomarker stratifying patients into low-risk and high-risk groups before surgery could identify patients who benefit from more extensive surgery. Therefore, we evaluated the correlation of serum biomarker HE4 with clinical and recently identified prognostic pathological variables and survival. Patients treated for endometrial cancer between 1994 and 2014 were included. Serum HE4 concentration was measured in preoperatively obtained samples. A total of 88 patients were eligible for analysis. The majority (64%) was diagnosed with endometrioid-type adenocarcinoma. Serum HE4 concentration is significantly associated with stage of disease (p=0.001), deep myometrial invasion (p<0.001), exact depth of myometrial invasion (≥4mm) (p=0.01), tumour-free distance to serosa (≤7mm) (p<0.001), extensive lymph vascular space invasion (p=0.04) and cervical involvement (p=0.001). HE4 concentration and nodal involvement were correlated, although not significant (p=0.17). Serum HE4 is an independent prognostic factor for recurrence-free survival (HR 5.12 per 10-fold increase in HE4, 95% CI 1.54-17.1) and overall survival (HR 7.48 per 10-fold increase in HE4, 95% CI 1.76-31.7). HE4 is a prognostic marker in endometrial cancer and is helpful in addition to other variables for the preoperative risk stratification of patients with endometrial cancer.

Predictive value of serum HE4 and CA125 concentrations for lymphatic metastasis of endometrial cancer.

To evaluate the predictive value of serum HE4 and CA125 concentrations in the preoperative prediction of risk of lymph node metastasis in endometrial cancer. A retrospective study was undertaken of data for patients with endometrial carcinoma treated surgically at a university hospital in China between August 2011 and December 2015. The preoperative serum levels of HE4 and CA125 were measured and analyzed by clinicopathologic characteristics. Overall, 258 patients were included. The HE4 and CA125 concentrations were significantly elevated in patients with large lesions (≥2cm), deep myometrial invasion (≥50%), an advanced disease stage, or lymph node metastasis (P<0.05 for all). HE4 concentrations also rose with age and histologic grade (P<0.01 for both). For lymph node metastasis, HE4 had higher sensitivity and negative predictive value than did CA125. The diagnostic performance of HE4 and CA125 in combination was superior to that of either marker alone. The combined evaluation of serum HE4 and CA125 could provide gynecologic oncologists with improved information to guide the decision of whether to perform lymphadenectomy.

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

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. 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. 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. 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.

Diagnostic performance and establishment of reference limits of HE4 in Korean healthy women

ObjectiveWe aimed to establish distribution and reference limits of HE4 and risk of ovarian malignancy algorithm (ROMA) in healthy Korean women and investigated the factors influencing HE4 levels. We also investigated the diagnostic performances of HE4 and ROMA score, compared with CA125. MethodsWe collected specimens from 1809 healthy Korean women, 140 specimens from patients with ovarian cancers (OCs) and 123 specimens from patients with benign ovarian tumor. Serum HE4 and CA125 concentrations were measured using an electrochemiluminescence immunoassay. The receiver operator characteristic (ROC) curve analysis was done for ROMA, HE4, CA125 and combining of HE4 and CA125. ResultsHE4 level was influenced by age, not by menopausal status. The 97.5th percentile upper reference limit of HE4 of subjects <50years and ≥50year-old was 63.87pmol/L and 88.28pmol/L, respectively. The 97.5th percentile upper reference limits of ROMA score were 13.66 in premenopausal and 19.30 in postmenopausal women. The serum HE4 level was even lower in the patients with benign tumor compared to those in healthy controls. HE4 had significantly higher concentrations in OCs than benign ovarian tumor (P<0.001). ROMA and HE4 combined with CA125 or not performed better diagnostically than CA125 alone for distinguishing OCs, with AUCs of 0.844 for ROMA, 0.827 for combining of HE4 and CA125, 0.825 for HE4, and 0.795 for CA125. ConclusionsThe reference limit of HE4 was different from those reported by other studies, suggesting racial or regional difference. HE4 and ROMA were better than CA125 for differentiation normal and benign ovarian tumor from OCs. (Word count: 253)

Value of serum human epididymis secretory protein 4 as a marker for differential diagnosis of malignant and benign gynecological diseases of patients in southern China

BackgroundThis study investigated the clinical value of HE4 in distinguishing malignant and benign gynecological diseases of patients in southern China. MethodsPreoperative serum CA125 and HE4 concentrations were tested in samples of women with malignant or benign gynecological diseases using fully automated methods (Abbott ARCHITECT) and validated cutoff values. ResultsFor the discrimination of ovarian cancer from benign gynecological diseases, in premenopausal women, the sensitivity and specificity were 89.8% and 67.5% for CA125, 68.5% and 97.8% for HE4, and 88.9% and 78.6% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 86.6% and 88.9% for CA125, 57.3% and 100% for HE4, and 85.4% and 94.4% for ROMA. For the discrimination of endometrial cancer from benign gynecological diseases, in premenopausal women, the sensitivity and specificity were 20.3% and 67.5% for CA125, 56.8% and 97.8% for HE4, and 74.3% and 78.6% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 17.8% and 88.9% for CA125, 31.5% and 100% for HE4, and 32.9% and 94.4% for ROMA. ConclusionsWe showed that HE4 had better specificity than CA125 in discriminating ovarian cancer, and endometrial cancer from benign gynecological diseases in southern China population.

Serum concentrations of HE4 change little during in vitro fertilization

Human epididymal secretory protein 4 (HE4) is a biomarker for ovarian cancer. The effect of follicle stimulating hormone (FSH) stimulation during in vitro fertilization (IVF) on HE4 was evaluated to determine whether substantial hormonal stimulation of the ovaries affects the serum levels of this marker. Findings were compared with serum concentrations of cancer antigen 125 (CA125), currently the most commonly used marker for ovarian cancer. Prospective cohort study. University hospital infertility clinic. Infertility patients undergoing IVF treatment. We determined the serum concentration of HE4 and CA125 in serial blood samples in 20 women treated with IVF. Samples were taken following gonadotrophin-releasing hormone agonist suppression, two to three times during FSH stimulation, at ovum pick-up and 2weeks following embryo transfer at the time of the pregnancy test. Ovarian follicles were counted and serum estradiol concentrations measured throughout treatment. Serum HE4, CA125 and estradiol concentrations. Serum HE4 levels did not increase significantly during the FSH stimulation. The majority of values remained below the normal reference range (<70pm) throughout the treatment. Serum CA125 concentration also remained low during stimulation. Serum estradiol concentration reflected the severity of ovarian stimulation during IVF, increasing 3.9-fold with stimulation. Serum HE4 concentrations respond little if at all to supraphysiological ovarian stimulation, suggesting that the amount of circulating HE4 in women with normal ovaries is independent of gonadotropin stimulation. Hormonal stimulation of the ovaries is unlikely to affect the differential diagnosis of ovarian tumors with HE4.

Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response

BackgroundHuman epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases.MethodsCA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively.ResultsSerum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively.ConclusionMeasuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759

Serum HE4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women

ObjectiveHuman epididymal secretory protein E4 (HE4) is a new promising tumor marker developed for the diagnostics and follow up of ovarian cancer. It has yet to become widely accepted in clinical practice, and its biological properties have not been inclusively studied. The aim of this study was to investigate whether serum HE4 concentration varies within the normal menstrual cycle and whether common gynecological hormonal treatments have an effect on HE4 values. MethodsOur study population consisted of 180 women, including 126 endometriosis patients and 54 healthy women. We measured their serum HE4 and CA125 concentrations and evaluated the effect of the menstrual cycle and the possible hormonal medication on these marker concentrations. ResultsWe found no significant variation in serum HE4 concentrations in samples taken at different phases of the menstrual cycle. The median HE4 concentrations in proliferative, secretory and menstrual phase were 41.5, 45.1 and 35.3pM in healthy women, and 43.4, 44.3 and 43.0pM in endometriosis patients, respectively. The use of combined estrogen and progestin contraceptives did not affect serum HE4 levels significantly. ConclusionsThe present study shows that the HE4 measurement in healthy premenopausal women as well as in women with endometriosis can be carried out at any phase of the menstrual cycle, and irrespective of hormonal medication, extending the benefits of HE4 use in clinical practice.

Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts

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.

Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts

Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts