Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers

Johnen, Georg; Burek, Katarzyna; Raiko, Irina; Wichert, Katharina; Pesch, Beate; Weber, Daniel G.; Lehnert, Martin; Casjens, Swaantje; Hagemeyer, Olaf; Taeger, Dirk; Brüning, Thomas

doi:10.1038/s41598-018-32315-3

Cited by 39 publications

(66 citation statements)

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“…Such an early detection approach has already been published for mesothelioma, reporting that sCRT (in combination with serum mesothelin) enabled prediagnostic detection of mesothelioma with an AUC of 0.74. 19 The biology and origin of CRT release into the bloodstream remains an open question. Since immunohistochemical studies on serous ovarian cancer reported variable CRT positivity in 0-40%, 15 it is possible that CRT promotes growth and survival of ovarian cancer cells, as it has been shown in vitro for mesothelioma.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations of sCRT were determined as described by Johnen et al ., using the commercially available Calretinin enzyme‐linked immunoabsorbent assay kit by DLD Diagnostika GmbH . The assay is based on polyclonal antibodies developed by Raiko et al .…”

Section: Methodsmentioning

confidence: 99%

“…Concentrations of sCRT were determined as described by Johnen et al, using the commercially available Calretinin enzyme-linked immunoabsorbent assay kit by DLD Diagnostika GmbH. 19 The assay is based on polyclonal antibodies developed by Raiko et al 20,24 All reagents and samples were equilibrated to room temperature (20-25 C) and the incubations were performed at room temperature (20-25 C) using a plate shaker. Serum samples (2 × 15 μl) were diluted 1:5 in the provided dilution buffer.…”

Section: Detection Of Scrtmentioning

confidence: 99%

“…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% .…”

Section: Introductionmentioning

confidence: 99%

“…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%).…”

Section: Introductionmentioning

confidence: 99%

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

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Passek

Wimberger

et al. 2019

Intl Journal of Cancer

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Calretinin (CRT) is a calcium‐binding protein that controls intracellular calcium signaling. Besides its prominent expression in neurons, serum CRT (sCRT) has recently been suggested as blood‐based biomarker for prediagnostic mesothelioma detection. CRT is expressed in ovarian cancer tissues in up to 40% of cases; however, its clinical relevance as blood‐based biomarker for ovarian cancer is unknown. sCRT was determined by calretinin enzyme‐linked immunoabsorbent assay (Calretinin‐ELISA, DLD Diagnostika GmbH, Hamburg, Germany) in a total of 515 serum samples from 116 healthy controls and 134 ovarian cancer patients (thereof 86% with Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] III/IV), including samples at primary diagnosis and at four longitudinal follow‐up time points in the course of treatment and at recurrence. sCRT level was significantly increased in ovarian cancer patients compared to healthy controls (estimated difference = 0.3 ng/ml, p < 0.001), was mostly independent from CA125 (r ≤ 0.388) and enabled accurate discrimination between cases and controls (area under the curve = 0.85). Higher sCRT level at primary diagnosis predicted suboptimal debulking (p < 0.001) and was associated with advanced FIGO‐stage (p < 0.001) and increased amount of ascites (p < 0.001). sCRT levels at primary diagnosis and its dynamics in the course of chemotherapy were independent predictors for poor progression‐free survival (hazard ratio [HR] = 1.99, confidence interval [CI] = [1.13–3.52], p = 0.0181) and overall survival (HR = 15.4, CI = [1.92–124], p = 0.0099). Furthermore, sCRT at primary diagnosis or a relative sCRT increase in the time interval between surgery and the onset of chemotherapy were both independent predictors of platinum resistance (OR = 4.99, CI = [3.50–16,001], p = 0.0016; OR = 2.41, CI = [1.37–6,026], p = 0.0271, respectively). This is the first study that suggests sCRT as liquid biopsy marker for independent prediction of platinum resistance and prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Detection Of Scrtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

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Passek

Wimberger

et al. 2019

Intl Journal of Cancer

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Malignant Pleural Mesothelioma

Carbone¹,

Gomez²,

Tsao³

et al. 2023

Holland‐Frei Cancer Medicine

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Overview Malignant pleural mesothelioma is an aggressive malignancy with an incidence that may be peaking worldwide. While the majority of patients do ultimately die of this disease, there have been substantial treatment and diagnostic shifts over the past decade that may improve long‐term outcomes. These changes include worldwide interest in defining early detection biomarkers for the disease, a debate as to the optimal surgical approach (extrapleural pneumonectomy vs lung‐sparing methods such as pleurectomy/decortication), further refinement of radiation techniques that allow for conformal treatment fields and the delivery of radiation with the involved lung intact, and the emergence of systemic therapies that are targeted in nature and allow for the increased individualization of care. Indeed, prospective clinical trials assessing the safety and efficacy of novel treatment approaches will be essential to the standardization of paradigms that improve outcomes. It is hoped that the maturation of these efforts will lead to an optimal approach in which earlier stage patients will benefit from multiple modalities that will provide synergistic control while limiting toxicity, thereby increasing the number of long‐term survivors over the next one to two decades.

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Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos‐related lung or pleural diseases

Taeger

Wichert

Lehnert

et al. 2022

American J Industrial Med

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Background Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos‐related lung or pleural diseases. Methods Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos‐related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI). Results We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57–23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98–1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51–19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76–1.41). The highest lung‐cancer risk (SIR: 2.56; 95% CI 1.10–5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen. Conclusions Compared to the general population, we demonstrated an association between benign asbestos‐related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung‐cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

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Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers

Cited by 39 publications

References 54 publications

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

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

Malignant Pleural Mesothelioma

Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos‐related lung or pleural diseases

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