Shed HER2 surrogacy evaluation in primary breast cancer patients: a study assessing tumor tissue HER2 expression at both extracellular and intracellular levels.

The aim of the present study was to investigate serum HER2 extracellular domain (ECD) as a putative surrogate marker of the shedding phenomenon of HER2 receptor from the tumor tissue of primary breast cancer (BC) patients. A pilot retrospective study was conducted on 100 matched serum and tissue samples from patients with node-positive primary BC, stage II/III. Analysis of association and concordance between serum HER2 ECD levels (measured by chemiluminescence immunoassay) and the expression in matched tumor tissue of HER2 ECD and intracellular receptor domain (ICD) (determined by immunohistochemistry) were performed. The median serum HER2 ECD level was 9.4 ng/ml and cutoff values were set at 15.2 ng/ml or 13.0 ng/ml. HER2 ICD and ECD were overexpressed in tumor tissue of 19.8% and 6.9% of patients, respectively. Statistically significant associations were found between serum HER2 ECD levels and tissue expression of both HER2 ICD and ECD (p < .001; Fisher analysis). Moreover, strong concordances were found between serum HER2 ECD levels and tissue expression of HER2 ICD or ECD (cutoff 15.2 ng/ml: 80 and 92.5%, respectively). Our findings support a role for serum HER2 ECD as a surrogate marker of tissue HER2 status in primary BC, both for HER2 ICD or ECD expression.

Evaluation of a sex hormone-binding globulin automated chemiluminescent assay.

BACKGROUND: Sex hormone-binding globulin (SHBG) is the main transport protein of sex steroids. This study evaluated the analytical performance of the recently developed Access SHBG assay (Beckman Coulter) and compared it with other commercial methods for the determination of serum SHBG. Clinical validation was also performed. METHODS: Analytical performance including within-run and between-run imprecision was assessed for Access SHBG assay on the automated Beckman UniCel DxI800 analyzer. Linearity was assessed using five dilutions of the serum samples. For methods comparison, SHBG levels were determined also with Immulite 2000 analyzer (Siemens Healthcare) using clinical serum samples (n = 104). For clinical validation 135 specimens from healthy subjects, pregnant women, hypothyroid and hyperthyroid patients were analyzed. RESULTS: Total coefficients of variation were < 5.5%. Linearity test showed > 90% recovery for all samples and for all dilution rates. Comparison analysis (Bland-Altman difference analysis and Passing-Bablock regression) showed an acceptable agreement between selected methods. SHBG values measured by Access SHBG assay in different groups of subjects were in agreement with other clinical evidence. CONCLUSIONS: Automated Access SHBG assay appears to be a reliable and easy to perform assay, as necessary for application in routine diagnostics.

Development of a website and biobank database for the Nanosized Cancer Polymarker Biochip Project: a Multicenter Italian Experience.

The Nanosized Cancer Polymarker Biochip Project (RBLA03S4SP) funded by an Italian MIUR-FIRB grant (Italian Ministry of University and Research - Investment Funds for Basic Research) has led to the creation of a free-access dynamic website, available at the web address https://serviziweb.ulss12.ve.it/firbabo, and of a centralized database with password-restricted access. The project network is composed of 9 research units (RUs) and has been active since 2005. The aim of the FIRB project was the design, production and validation of optoelectronic and chemoelectronic biosensors for the simultaneous detection of a novel class of cancer biomarkers associated with immunoglobulins of the M class (IgM) for early diagnosis of cancer. Biomarker immune complexes (BM-ICs) were assessed on samples of clinical cases and matched controls for breast, colorectal, liver, ovarian and prostate malignancies. This article describes in detail the architecture of the project website, the central database application, and the biobank developed for the FIRB Nanosized Cancer Polymarker Biochip Project. The article also illustrates many unique aspects that should be considered when developing a database within a multidisciplinary scenario. The main deliverables of the project were numerous, including the development of an online database which archived 1400 case report forms (700 cases and 700 matched controls) and more than 2700 experimental results relative to the BM-ICs assayed. The database also allowed for the traceability and retrieval of 21,000 aliquots archived in the centralized bank and stored as backup in the RUs, and for the development of a centralized biological bank in the coordinating unit with 6300 aliquots of serum. The constitution of the website and biobank database enabled optimal coordination of the RUs involved, highlighting the importance of sharing samples and scientific data in a multicenter setting for the achievement of the project goals.

Osteopontin, asbestos exposure and pleural plaques: a cross-sectional study.

BACKGROUND: Osteopontin (OPN) is a plasma protein/cytokine produced in excess in several malignancies. In a recent study OPN was reported as being related to the duration of asbestos exposure and presence of benign asbestos-related diseases; however, it was unclear whether this protein was an indicator of exposure or effect. METHODS: In 193 workers, 50 with pleural plaques (PP), in whom different indicators of past asbestos exposure were estimated, OPN plasma levels were assessed using commercial quantitative sandwich enzyme immunoassays according to the manufacturer's instructions. RESULTS: Osteopontin increased with increasing age and several aspects of asbestos exposure, without differences related to the presence of pleural plaques. At multivariable regression analysis, the explanatory variables with a significant independent influence on OPN were length of exposure (positive correlation) and time elapsed since last exposure (positive correlation). CONCLUSIONS: Since asbestos in lung tissue tends to wane over time, OPN should decrease (rather than increase) with time since last exposure. Therefore, OPN cannot be a reliable biomarker of exposure nor effect (presence of pleural plaques).

Serial determination of CEA and CA 15.3 in breast cancer follow-up: an assessment of their diagnostic accuracy for the detection of tumour recurrences.

We studied the diagnostic accuracy of carcinoembryonic antigen (CEA) and cancer antigen 15.3 (CA 15.3) in detecting breast cancer recurrence. Biomarker follow-up determinations, made over 900 patients, were related to local-regional or distant recurrence using statistical models for longitudinal data. The diagnostic accuracy was quantified in terms of sensitivity, specificity and Youden index. The biomarkers were poorly predictive of local-regional recurrence. As for distant recurrence, the best diagnostic accuracy was obtained considering the two biomarkers jointly and combining two positivity criteria: a value above the normal limit or a difference between two consecutive measurements greater than the critical difference for at least one biomarker. A third criterion, based on within-patient comparison between follow-up determinations and a baseline, failed to improve the above result. CEA and CA 15.3 might play a role in patient monitoring during follow-up for the search of distant recurrence.