Evaluation of a CLEIA automated assay system for the detection of a panel of tumor markers.

Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.

Serum HE4 levels combined with CE CT imaging improve the management of monitoring women affected by epithelial ovarian cancer.

The aim of the present study was to evaluate human epididymis protein 4 (HE4) as a marker of epithelial ovarian cancer (EOC) relapse and the combination of this biomarker with contrast-enhanced high-resolution multidetector row computed tomography CE CT imaging to impove the monitoring of EOC patients. Twenty-one patients with advanced EOC (FIGO III/IV) who underwent surgery and adjuvant chemotherapy were retrospectively selected. Each patient contributed 3 serum samples drawn at 3-month intervals: time interval I (1-3 months from surgery), time interval II (4-6 months from surgery) and time interval III (7-10 months from surgery). Serum HE4 and cancer antigen-125 (CA-125) levels were determined by EIA and IRMA assays, respectively. Nine out of the 21 (Group A) women had disease relapse while 12 out of the 21 (Group B) women had stable disease during the follow-up study. Twenty out of the 21 patients underwent at least two CE CT follow-ups with an interval time of ~6 months. One patient did not undergo a second CE CT. In patients with relapsed EOC, an increase in HE4 was noted in 22, 78 and 89% of patients within the time intervals I, II and III, respectively. Positivity for CA-125 was found later at time interval III and only in 44% of patients. Conversely, for EOC patients in remission, increase over the threshold level was observed only for marker CA-125 (4/12). The evaluation of imaging findings at interval time II showed a significant correlation with high levels of HE4 in 6 out of 9 patients with recurrent disease. This study supports the hypothesis that HE4 may serve as an early biomarker for recurrence of EOC. Moreover, HE4 serum levels combined with CE CT imaging may improve the monitoring management of women affected by ovarian cancer.

The use of HE4, CA125 and CA72-4 biomarkers for differential diagnosis between ovarian endometrioma and epithelial ovarian cancer.

BACKGROUND: Endometriosis is frequently associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish a panel of complementary biomarkers that could be helpful in the differential diagnosis between ovarian endometriosis or other ovarian benign masses and ovarian cancer. METHODS: Blood samples from 50 healthy women, 17 patients with benign ovarian tumors, 57 patients with ovarian endometrioma and 39 patients with ovarian cancer were analyzed and serum values were measured for the following biomarkers: CA125, HE4 and CA72-4. RESULTS: Serum CA125 concentration was elevated in both patients with ovarian endometriosis and ovarian cancer but not in patients with other benign ovarian masses. HE4 was never increased in patients with endometriosis or benign masses whereas it was significantly higher in all patients with ovarian cancer (p < 0.05). A marked difference in CA72-4 values was observed between women with ovarian cancer (67%) and those with endometriosis (p < 0.05). CONCLUSIONS: The results of the study suggest that HE4 and CA72-4 determination is the best approach to confirm the benign nature of ovarian endometrioma in women with high CA125 levels.