Determinants of plasma calretinin in patients with malignant pleural mesothelioma

Abstract

Objective: Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated. Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA). Results: The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23 ng/ml; p < 0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67 ng/ml; p = 0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.

Serum Calretinin as a Biomarker in Malignant Mesothelioma

“…At the cutoff value of 0.32 ng/mL, the specificity was high (89%), while the sensitivity was limited (68%). Consistent with our results, other studies to date have shown that patients with MM have higher levels of calretinin than other subjects who were also exposed to asbestos [ 8 , 21 , 30 ], suggesting calretinin behaves similarly to mesothelin and other biomarkers [ 30 ]. Similar plasma calretinin cutoff values were observed in previous studies [ 8 , 23 ], while higher cutoff values were required to reach 95% or 98% predefined specificity [ 8 , 30 ], similar to our study.…”

“…We found that the concentration of calretinin was higher in women and a higher cutoff value was required to differentiate between MM patients and other subjects; however, the sensitivity was lower. This confirmed the results of other studies that also found higher levels of calretinin in small groups of women [ 21 , 24 ], except in one study evaluating plasma calretinin in a very small cohort of women from the Mexican population [ 23 ]. Other previous studies only evaluated calretinin levels in male subjects.…”

“…Most research in the field of MM biomarkers has been conducted only on the population of pleural MM [ 21 , 23 ]. In our study, we included patients with pleural and peritoneal MM.…”

“…In tumor samples, calretinin expression has been detected in up to 90% of MM patients with the epithelioid histological type, but only in up to 55% of patients with the sarcomatoid subtype [ 9 ]. In studies to date, the level of calretinin in tissue samples has been positively associated with the level of calretinin in plasma in patients with pleural MM [ 21 ]. A few recent studies showed that calretinin was increased also in the plasma or serum of MM patients compared to occupationally exposed subjects with other asbestos-related diseases or healthy controls [ 8 , 22 , 23 , 24 ].…”

Serum Calretinin and Genetic Variability as a Prognostic and Predictive Factor in Malignant Mesothelioma

“…Consistent with previous studies, higher calretinin mRNA expression was associated with longer OS in the TCGA MESO cohort. So far, the association between tissue calretinin expression and soluble calretinin in MM was only investigated in one study: patients with calretinin-positive tumors had higher plasma calretinin [ 29 ], and, therefore, a similar prognostic role in tissue and blood could be expected. However, the positive correlation of calretinin expression in tissue and plasma could be attributed to the fact that calretinin is more often detected in epithelioid and biphasic MM compared to the sarcomatoid subtype in both tissue and plasma or serum of MM patients [ 18 , 20 , 30 , 31 ].…”