Biomarkers in malignant mesothelioma: diagnostic and prognostic role of soluble mesothelin-related peptide.

Soluble mesothelin-related peptide (SMRP) is a biomarker that has been proposed for differential diagnosis from pleural metastatic cancer, as well as prognosis and treatment monitoring of malignant pleural mesothelioma (MM). The aim of this study was to evaluate the role of SMRP in clinic management of MM. We assayed the SMRP concentrations in 354 subjects: 109 healthy volunteers with no history of exposure to asbestos, 26 patients with previous occupational asbestos exposure but who were free from pleural or parenchymal disease, 48 patients with asbestosis, 110 patients with pleural plaques, 25 patients with lung cancer, and 36 patients with MM. We also tested SMRP titers in 2 patients with MM at 5 different times of the disease, to evaluate the trend of the biomarker in the course of therapy. Our data confirm previous experiences with the use of SMRP as a diagnostic marker of MM. Low SMRP levels at diagnosis seem to have a positive prognostic significance.

Mesothelin family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results.

BACKGROUND: Studies have suggested that soluble mesothelin-related protein (SMRP) can be used as a serum marker of malignant mesothelioma. METHODS: We assessed the analytical performance of the Mesomark (Fujirebio Diagnostic) two-step ELISA on an automated analyser and performed a preliminary clinical evaluation. The precision of the assay and the in vitro effect of interfering substances on SMRP concentrations were investigated. The serum marker was analysed in 109 healthy subjects never exposed to asbestos, 26 healthy subjects exposed to asbestos, 33 patients with asbestosis, 33 with asbestos-related pleural plaques, 10 with non-malignant pleural diseases, 30 with lung cancer and 24 with histological diagnosis of pleural mesothelioma. RESULTS: Using the International Mesothelioma Interest Group classification, there were nine stage IV, two stage III, four stage II and nine stage I patients. SMRP concentrations of 4.75, 11.0 and 14 nmol/mL showed a total imprecision of 3.5%, 3.1% and 3.8%. The detection limit was 0.035 nmol/mL; the mean SMRP concentration of 0.63 nmol/mL was associated with a coefficient of variation of 10%. There was no effect (p>0.05) of interfering substances. Serum samples from patients with established pleural mesothelioma had significantly higher (p<0.05) concentrations of SMRP than control healthy and patient groups. CONCLUSIONS: SMRP measured on automated systems could be useful for the diagnosis of mesothelioma in routine clinical practice.

[RANKL/RANK, OPG and OPT in a group of patients affected by chronic arthritis. Preliminary report]. / Il sistema RANK/RANK, osteoprotegerina e osteopontina in una coorte di soggetti affetti da poliartrite cronica. Studio preliminare.

Recently, receptor activator of nuclear factor-kappaB ligand (RANKL), its receptor RANK, and the decoy receptor osteoprotegerin (OPG), have been identified as paracrine mediator of bone functions. The balance of RANKL/RANK and OPG is critical for osteoclastogenesis modulation and physiological bone remodeling. Osteopontin (OPN) is an extracellular glycosylate bone phosphoprotein and acts both as chemokine and cytokine. It is produced by osteoclast, macrophages, T cells, hematopoietic cells and vascular smooth muscle cells. It is present particularly at high concentration in the lamina limitans and cement line, suggesting its role in the initiation and termination of the bone turnover. Chronic arthritis are a group of rheumatic pathologies characterized by periodical continuous or desultory use of corticosteroids. The main aims of this study are to evaluate OPG, RANKL and OPN serum concentrations in patients affected by chronic arthritis and to compare the above results with those ones obtained by young healthy population. OPG, RANKL and OPN serum concentration has been measured by ELISA method both in 40 patients affected by chronic arthritis then in young healthy population of 81 subjects. The differences between the two considered groups have been analyzed using unpaired T-Student. The difference between the two groups is significant for considered variables: OPG: t = -6.54, p < 0.001; RANKL: t = -2.71, p = 0.008; OPN: t = 2.55, p = 0.01. These results suggest that RANKL/RANK system,OPG and OPN have important role in patients with chronic arthritis.

Anti-cyclic citrullinated peptide autoantibodies measured by an automated enzyme immunoassay: analytical performance and clinical correlations.

BACKGROUND: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the analytical performance and clinical correlation of an automated enzyme immunoassay (DSX, DINEX Technologies), for the detection of anti-CCP autoantibodies (DIASTAT anti-CCP, Axis-Shield, DUNDEE UK). METHODS: Commercial controls and serum pools were used to determine its precision, analytical sensitivity, functional sensitivity and linearity. Sera from 83 patients with established RA and from 140 controls, including patients with various autoimmune diseases, viral infections and cancer, as well as sex- and age-matched healthy subjects, were studied. The rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP findings. RESULTS: The total imprecision (CV%) was 4.7-7.2% for concentrations ranging between 1.98 and 71.81 U/mL. The lower detection limit was 0.038 U/mL. At a cut-off of 5 U/mL, the sensitivity and specificity for RA were 67.5% and 99.3%, respectively. The RF had a sensitivity of 66.3% and a lower specificity 82.1% than anti-CCP. When the two antibodies were used together, the specificity was 99.1%. CONCLUSIONS: The anti-CCP assay we examined on a fully automated system showed a good analytical performance (analytical and functional sensitivity, linearity) and good clinical correlation. We conclude that this system can provide rapid, useful data.