Calretinin as a blood-based biomarker for mesothelioma

Abstract

BackgroundMalignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.MethodsFor a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.ResultsCalretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10–3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30–4.00).ConclusionsCalretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3375-5) contains supplementary material, which is available to authorized users.

Serum calretinin as an independent predictor for platinum resistance and prognosis in ovarian cancer

“…Informed written consent was obtained from all donors, and the study was approved by the Local Research Ethics Committee in Dresden (EK74032013). There was no correlation between sCRT and age as confirmed by our own data set ( p = 0.15) and by previous studies . Nevertheless, individuals for blood donation were selected in an age range matching the included ovarian cancer patients, with the majority of donors ranging between 50 and 75 years.…”

“…sCRT was highly elevated at primary diagnosis of ovarian cancer and accurately discriminated cases from healthy controls (AUC = 0.85), which is comparable to a study on German and Australian mesothelioma patients, reporting on sCRT elevation in patient blood and a discrimination of cases and controls with an AUC of 0.83 and 0.91, respectively. 20 We additionally reported that sCRT allows, albeit with less discriminative power, detection of particularly early disease (FIGO I-II; AUC = 0.67). However, this analysis was based on only 19 patients and does not allow a statistically substantiated conclusion.…”

“…There was no correlation between sCRT and age as confirmed by our own data set (p = 0.15) and by previous studies. 20 Nevertheless, individuals for blood donation were selected in an age range matching the included ovarian cancer patients, with the majority of donors ranging between 50 and 75 years. Furthermore, serum preparation of control samples was performed with exactly the same protocol as for the patient samples to ensure comparability.…”

“…CRT is expressed in several epithelial and nonepithelial tumor entities, especially in mesotheliomas, in which it is used as an immunohistochemical marker to differentiate mesotheliomas from adenocarcinomas . The diagnostic impact of CRT for mesothelioma has recently been transferred to a liquid biopsy approach, in which plasma CRT was suggested as blood‐based marker for mesothelioma detection, particularly in a prediagnostic setting . Among malignancies of the female genital tract, CRT expression has commonly been reported in sex cord stromal tumors with an expression rate ranging from 40% up to 100% .…”

“…18 The diagnostic impact of CRT for mesothelioma has recently been transferred to a liquid biopsy approach, in which plasma CRT was suggested as blood-based marker for mesothelioma detection, particularly in a prediagnostic setting. 19,20 Among malignancies of the female genital tract, CRT expression has commonly been reported in sex cord stromal tumors with an expression rate ranging from 40% up to 100%. 15 There is evidence that CRT is variably expressed in ovarian cancer, with highest prevalence among serous histotypes (0-40%) followed by endometrioid subtypes (0-33%) and clear cell carcinomas (0-14%).…”