Value Of HE4 Research Articles

Clinical Evaluation of Human Epididymis Protein 4 as a Biomarker for Epididymitis

To evaluate HE4 as a potential biomarker for acute epididymitis. HE4 levels in serum were measured in 62 patients with acute epididymitis and 62 age-matched male controls. Both patients with epididymitis and the controls showed median HE4 values of 42 pmol/l (range: 10-560 pmol/l) and 34 pmol/l (range: 2-300 pmol/l), respectively (p = 0.3). Levels of HE4 did not change in the course of the treatment in patients with epididymitis. Regression analysis revealed no significant association between HE4 and any infection-linked variable. Multivariate analysis resulted in a number of factors associated with increased HE4 levels, which were renal dysfunction, cardiovascular diseases and malignancies. Although HE4 is not a biomarker for epididymitis and infection, it qualifies as a candidate for identifying patients with increased morbidity.

HE4 is an independent prognostic marker in endometrial cancer patients

ObjectiveTo evaluate the prognostic value of pretherapeutic serum HE4 in endometrial cancer in comparison to CA125. MethodsHE4 and CA125 serum levels were analyzed by means of chemiluminescent microparticle immunoassays in 183 patients with endometrial cancer treated at the Department of Obstetrics and Gynecology, Innsbruck Medical University, between 1999 and 2009. The Kaplan–Meier method and Cox's proportional hazards analysis were performed to determine the prognostic significance of HE4, CA125 and the combination of both markers. ResultsIn univariate analysis both markers, HE4 and CA125, were of prognostic value for overall survival (p<0.001 and p=0.028) and disease-free survival (p=0.015 and p=0.045). In multivariate analysis HE4 was seen to have independent prognostic value in overall survival (HR 2.407, p=0.017) in contrast to CA125. The combination of both markers showed a higher hazard ratio (HR 4.04, p=0.023) for overall survival in comparison to HE4 alone. In the subgroup endometrioid histological type (n=132) only HE4 was of prognostic value for overall survival in univariate (p=0.001) and multivariate analysis (p=0.023). ConclusionsPretherapeutic serum HE4 levels alone and in combination with CA125 are an independent prognostic marker in endometrial cancer patients.

Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.

HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma

The purpose of the study was to evaluate the expression of the biomarkers CA125 and HE4 combined with imaging, in patients with advanced epithelial ovarian cancer (EOC). Forty-six women with EOC were included in the study all affected with peritoneal carcinomatosis. Twenty-two of 46 patients (group I) had peritoneal carcinomatosis with small implants in single or in multiple sites (score 1); 24/46 patients (group II) had macro-nodular implants and omental thickening (score 2). High levels of CA125 (350 ± 11, mean ± SEM) have been observed in 21/22 patients of group I, and a similar value (370 ± 13) has been observed in all patients belonging to group II. HE4 positivity values (350 ± 9) have been observed in all group I patients, whereas all patients belonging to group II showed a higher value of HE4 (600 ± 12). Statistically significant differences were observed between the HE4 levels observed in group I patients in comparison with group II patients (p < 0.0001). In addition, we expressed the extension of lymph nodal disease in three scores: L1-L2-L3, and a statistically significant correlation was observed between high HE4 levels and severity of lymph nodal disease L3 (p < 0.0001). The availability of biomarkers, particularly HE4, together with sophisticated imaging techniques, strengthens the clinical relevance of this study, for the follow-up of patients with peritoneal carcinomatosis.

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 Profile During Primary Chemotherapy of Epithelial Ovarian Cancer

Human epididymis protein 4 (HE4) is a promising novel serum biomarker for the detection of early-stage epithelial ovarian cancer (EOC) and for the differential diagnosis between benign and malignant ovarian tumors. The objective of the present study was to determine the value of HE4 for monitoring the response to primary therapy in patients with advanced disease. Serum HE4 and cancer antigen (CA) 125 levels of 10 patients with advanced EOC and one patient with adenocarcinoma of unknown origin were measured preoperatively and during first-line chemotherapy. Seven patients were treated with primary surgery and six cycles of chemotherapy. Response to treatment was evaluated 4 weeks after the completion of chemotherapy using computed tomography. Four patients received neoadjuvant chemotherapy (NACT) before surgery. To evaluate the early response to chemotherapy, changes in serum biomarker levels were compared with metabolic changes of tumors during NACT as detected by positron emission tomography/computed tomography. The profile of HE4 during primary chemotherapy was in line with radiologic and clinical responses. In the neoadjuvant chemotherapy group, HE4 correlated better with the radiologic response than CA 125. Assessment of serum HE4 may improve the reliability of response evaluation during chemotherapy for serous epithelial ovarian cancer.

Recent advances in the biomarkers for epithelial ovarian cancer

Recent advances in the biomarkers for epithelial ovarian cancer

Abstract 4653: Role of serum HE4 in studying ovarian cancer progression and response to therapy with ARCHITECT HE4 assay

Abstract Human epididymis protein 4 (HE4) is a whey acidic four-disulfide core protein. Serum HE4 has been shown to be a promising biomarker for epithelial ovarian cancer (EOC) with manual HE4 EIA assays. The ARCHITECT system is one of the major automated formats for cancer immunodiagnostics. This abstract describes the clinical performance of an investigational ARCHITECT HE4 assay in the measurement of serum HE4 from longitudinal samples of subjects with EOC and single-point samples from healthy subjects, and subjects with malignancy, benign diseases, EOC or other malignant diseases. PROCEDURES: The ARCHITECT HE4 Assay is a paramagnetic microparticle chemiluminescent assay adopting the sensitive CHEMIFLEX® technology. Single-point and longitudinal serum samples were tested with an investigational ARCHITECT HE4 Assay reagent lot on the ARCHITECT i2000SR. Single-point sera were collected from healthy subjects (N = 400), subjects with pregnancy (N = 50) and benign disease (N = 612), and subjects which were diagnosed with EOC (N = 314) and other cancers (N = 250) including endometrial, breast, gastrointestinal, lung, and bladder cancer. Longitudinal sera (N = 506), including initial time point and follow-up visits (average = 5.7 per subject), were collected from subjects (N = 76) which were diagnosed with EOC. All of the single-point and longitudinal samples were handled in accordance with IRB-approved and GCP-compliant protocols. RESULTS: Using an ARCHITECT HE4 cut-off value of &amp;gt;140 pmol/L, the percent distributions of ARCHITECT HE4 by cohort are: 3% of healthy subjects, 0% with pregnancy, 7.2% of subjects with benign diseases, 53.5% with EOC and 28.4% with other cancers. Using the upper 95% point of the distribution of the HE4 ratio at 14% to categorize the successive HE4 readings into those that were and were not significantly elevated for the longitudinal samples, the sensitivity, specificity and positive predictive value of HE4 elevation versus disease progression were 53.4% (95% CI: 44.1%-62.5%), 78.8% (95% CI: 74.7% - 82.4%) and 43.2% (95% CI: 32.9% - 54.1%) respectively. The total concordance between HE4 elevation and disease progression was 73%. Receiver Operator Characteristic analysis showed an area under the curve of 0.685 (SE = 0.033) for the diagnosis of progression from the ratio of successive HE4 readings. When comparing the change of the HE4 ratio with the diagnostic response to therapy, a decrease in HE4 reflected response to therapy with a sensitivity of 82% and a specificity of 53%. CONCLUSIONS: The study with single-point samples has shown the utility of ARCHITECT HE4 values as a serum biomarker for EOC. The longitudinal increase of ARCHITECT HE4 values in sera seemed to be effective in recognizing the progression of EOC. The longitudinal decrease of ARCHITECT HE4 values in sera seemed to correlate with the response of EOC subjects to therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4653.

P53 Autoantibodies as Potential Detection and Prognostic Biomarkers in Serous Ovarian Cancer

This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer. p53-AAb were detected by ELISA in sera obtained preoperatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (n = 60), nonserous ovarian cancers (n = 30), and women with benign disease (n = 30). Age-matched controls were selected from the general population (n = 120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival. p53-AAb were detected in 25 of 60 (41.7%) of serous cases, 4 of 30 (13.3%) nonserous cases, 3 of 30 (10%) benign disease cases, and 10 of 120 (8.3%) controls (combined P = 0.0002). p53-AAb did not significantly improve the detection of cases [area under the curve (AUC), 0.69] or the discrimination of benign versus malignant disease (AUC, 0.64) compared with CA 125 (AUC, 0.99) or HE4 (AUC, 0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (P = 0.01). Detectable p53 antibodies in pretreatment sera were correlated with improved overall survival (P = 0.04; hazard ratio, 0.57; 95% confidence interval, 0.33-0.97) in serous ovarian cancer. Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer. Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.

Use of a novel biomarker HE4 for monitoring patients with epithelial ovarian cancer

5535 Background: The serum biomarker CA125 is effectively used for monitoring response to therapy and monitoring for recurrent disease in patients with epithelial ovarian cancer (EOC). However, CA 125 is not elevated in approximately 20% of patients. The novel tumor marker HE4 has been shown to be elevated in the majority of EOC patients as well as in patients that do not express CA125. The object of this study was to determine the concordance between HE4 and CA125 in patients being followed with EOC. Methods: This was a retrospective study utilizing serum samples obtained from an IRB approved serum bank. Serial samples from patients either undergoing treatment for EOC or being monitored for recurrence were obtained. Clinical status of the patients was assessed through serial CA125 and CT imaging with documentation of regression or progression of disease or absence of disease over time. Serum CA125 and HE4 levels were measured using the Architect CA 125II assay and the HE4 EIA assay. Serial changes in the serum CA125 and HE4 levels were compared to the documented clinical status using a cutoff of 25%. Concordance between HE4 and CA125 was determined and the performance of CA125 and HE4 was compared directly using a non-inferiority approach. Results: A total of 434 serial samples from 80 patients either undergoing treatment for EOC or being monitored for recurrence were obtained. Longitudinal analysis of the serum sample sets showed that changes in HE4 values were not inferior to changes in CA125 values in accordance with clinical status (p=0.039). CA125 correlated with clinical status in 78.8% (63/80) and HE4 correlated in 76.2% (61/80). In patients where CA125 did not correlate with clinical status, HE4 correlated in 23.5% (4/17). In patients where HE4 did not correlate with clinical status, CA125 correlated in 31.6% (6/19). In consideration of all cases either CA125 or HE4 correlated with clinical status for 83.8% (67/80). Conclusions: HE4 is a valuable biomarker for the majority of patients with EOC and behaves in concordance with CA125 in patients with EOC. As well, HE4 is a valuable marker for the management of some patients where CA125 is not of clincal utility. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fujirebio Diagnostics, Inc Fujirebio Diagnostics, Inc, Thiel Statistical Consultants Fujirebio Diagnostics, Inc Fujirebio Diagnostics, Inc

Utility of a novel serum tumor biomarker HE4 in patients with uterine cancer

5036 Background: Approximately 40,880 new cases of uterine cancer are diagnosed in the U.S. annually resulting in 7,310 deaths. Uterine cancer is surgically staged and 75% of patients present with stage I disease. Patients with stage I tumors with intermediate to high risk factors have a recurrence rate of 20 to 30%. Serum CA125 is elevated in 75% of patients with advanced stage disease and in only 17% of patients with early stage disease. The use of CA125 for the detection of recurrent disease is limited at best. Only 25% of patients with asymptomatic recurrent disease have an elevated CA125. A better marker indicating early recurrent disease is needed. The objective of this study was to examine the value of a novel serum tumor marker HE4 in endometrial cancer. Methods: Serum samples from two prospective IRB approved studies at two institutions were analyzed to compare HE4 with CA125 in patients who had surgical staging for uterine cancer. Normal controls were obtained from healthy patients. Informed consent was obtained from all patients and blood samples were drawn pre-operatively. HE4 and CA125 levels were determined using assays from Fujirebio Diagnostic Inc. ROC curves were constructed for each tumor marker and the sensitivity at a set specificity of 95% was determined. Results: Serum from 156 controls and 233 patients with surgically staged endometrial cancer; (151 stage I, 21 stage II, 47 stage III and 14 stage IV) were examined. The area under the ROC curves (ROC-AUC) for HE4 and CA125 were determined and compared ( Table1 ). At 95% specificity, the sensitivity for differentiation of controls versus all stages was 44.9% for HE4 compared to 25.2% for CA125 (p = 0.0001). For stage I cases, HE4 showed an improvement in the sensitivity of 20.5% compared to CA125 (37.1% vs 16.6%, p = 0.0001). Conclusions: HE4 is elevated in all stages of endometrial cancer and has a greater sensitivity for discrimination from normal controls compared to CA125. As well, HE4 is elevated in early stage endometrial cancer and should be investigated as a marker for early recurrent disease. [Table: see text] [Table: see text]

Helium Production in the Different Cosmological Models

The aim of the present report is to emphasize the role of the helium problem as the key one for different aspects of cosmological speculations. This is not surprising, because the processes which produce the helium and other elements in primordial matter take place during the first stages of the cosmological expansion of the Universe.The theory gives three critical values of the He4 abundance in pre-stellar matter, depending on assumptions about the behaviour of the Universe near the singularity. The three critical values are:(1) practically no He4 at all;(2) about 25% of He4 by mass;(3) practically entirely He4.Although intermediate values of He4 are in principle possible, the cosmological models permitting such values are highly improbable. It is obvious that the helium abundance is less than 100%, and that even rough estimates of whether the stellar matter consists almost entirely of hydrogen, or if it has a significant part of He4, are of tremendous importance. The much-more-difficult determination of traces of primeval He3, D, Li6, would be of great help in making definite cosmological conclusions.

Quantum Corrections to the Second Virial Coefficient for Helium at High Temperatures

The high temperature quantum corrections to the second virial coefficient are calculated for a square-well repulsive core model. It is shown that the hard core correction is large for He4 at all temperatures for which present measurements exist. The correction can be verified experimentally, because it leads to a 5% difference between He4 and He3 values at high temperatures.