Determinants of plasma calretinin in patients with malignant pleural mesothelioma

Our plain-English summary of Determinants of plasma calretinin in patients with malignant pleural mesothelioma, by M. Lehnert, D.G. Weber, D. Taeger, et al (BMC Research Notes, 2020).

The study

• Authors: M. Lehnert, D.G. Weber, D. Taeger, I. Raiko, J. Kollmeier, S. Stephan-Falkenau, T. Brüning, G. Johnen, MoMar-Study Group
• Journal: BMC Research Notes
• Published: 2020;13(1):359
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This German cross-sectional study measured plasma calretinin, a protein used as a mesothelioma marker. It compared 60 patients with malignant pleural mesothelioma (54 men, 6 women), sampled at a pulmonary clinic between 2008 and 2017, with 111 cancer-free controls from the MoMar cohort. The controls had substantial past occupational asbestos exposure and benign asbestos-related diseases. The median plasma calretinin level was 0.79 ng/mL in patients and 0.23 ng/mL in controls (p < 0.0001). Levels were significantly higher than in controls for epithelioid (1.06 ng/mL) and biphasic (0.67 ng/mL) mesothelioma. Sarcomatoid mesothelioma (0.32 ng/mL) was similar to controls. Women with mesothelioma had higher levels than men, but there were only six women. Among 15 patients whose blood was drawn before surgery, stronger calretinin staining of the tumor went with higher plasma levels (p = 0.048). Patients sampled before surgery (16) had higher levels than those sampled after (44) (1.20 vs 0.67 ng/mL), a difference that was not statistically significant (p = 0.096). The authors found no clear association with the extent of disease. They noted that subgroups were small, so chance results cannot be excluded.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: cross-sectional survey comparing plasma calretinin (measured by ELISA) in mesothelioma patients and matched asbestos-exposed cancer-free controls
• Who was studied: 60 patients with malignant pleural mesothelioma (54 male, 6 female, aged 32 to 87, median 72) whose blood and clinical information were collected at a pulmonary clinic between July 2008 and April 2017, plus 111 cancer-free controls from the MoMar cohort matched by age, gender and smoking status
• Exposure: The study measured plasma calretinin, not asbestos dose. The controls had a history of substantial occupational asbestos exposure and benign asbestos-related diseases (asbestosis, pleural plaques, pleural thickening and/or pleural fibrosis). No fiber types are given, and the patients' asbestos exposure is not described.
• Main results:
  • Median plasma calretinin was 0.79 ng/mL (IQR 0.37 to 1.68) in the 60 mesothelioma patients and 0.23 ng/mL (IQR 0.16 to 0.33) in the cancer-free controls; the difference was statistically significant (p < 0.0001)
  • Median calretinin was significantly higher than in controls in epithelioid MPM (1.06 ng/mL, IQR 0.40 to 2.07) and biphasic MPM (0.67 ng/mL, IQR 0.41 to 1.28)
  • Sarcomatoid MPM showed calretinin levels (0.32 ng/mL, IQR 0.06 to 0.50) similar to the controls
  • Male MPM patients had a median of 0.66 ng/mL (IQR 0.36 to 1.50), reported as significantly lower than the median of 1.81 ng/mL in the six female MPM patients
  • No correlation was observed between age and calretinin concentration in MPM patients (rs = -0.144; p = 0.27)
  • Blood drawn before any surgical procedure had higher calretinin (1.20 ng/mL, IQR 0.47 to 2.42) than blood drawn afterwards (0.67 ng/mL, IQR 0.35 to 1.45), but the difference was not statistically significant (p = 0.096)
  • For 15 patients with preoperative blood samples, tumor tissue staining was scored: most tumors were calretinin-positive (H-score = 3) and three were calretinin-negative (H-score less than 3). Plasma levels differed between these groups, and the difference was just statistically significant (p = 0.048).
  • Among epithelioid and biphasic MPM patients with a recorded T stage, median calretinin was 1.06 ng/mL for T1 and 1.34 ng/mL for T2, compared with 0.45 ng/mL for T3 and 0.53 ng/mL for T4. No significance test was reported for these comparisons.
  • In 16 preoperative samples, median calretinin was 0.81 ng/mL (IQR 0.45 to 1.80) with a smaller tumor mass and 1.31 ng/mL (IQR 0.88 to 2.76) with a larger tumor mass; the difference was not statistically significant (p = 0.23)
• The authors' conclusion: The authors concluded that patients with epithelioid or biphasic MPM showed higher calretinin than cancer-free controls with benign asbestos-related diseases. They found that tumor staining intensity was positively associated with plasma calretinin and that a clear association with extent of disease could not be demonstrated. They suggested that trends toward lower levels after surgical debulking may indicate a benefit in monitoring therapy and disease progression.
• Limitations the authors state:
  • Subgroups contained small numbers of patients, so random effects cannot be excluded
  • Only 16 patients gave blood before thoracic surgery and 44 after; the authors called for larger studies with a balanced gender ratio and defined sampling times, and for samples collected prospectively during treatment
  • Only six women were included, so the sex difference could be a chance result
  • Tumor stage was incompletely documented: valid T stages were available for 35 of 60 cases

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Calretinin, Pleural Mesothelioma, Malignant Mesothelioma, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Thoracic Surgery, Tumor Marker.

Related studies

• Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients — I. Raiko, I. Sander, et al. (2010)
• Calretinin as a blood-based biomarker for mesothelioma — G. Johnen, K. Gawrych, et al. (2017)
• Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers — G. Johnen, K. Burek, et al. (2018)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)
• Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany — H.P. Rihs, S. Casjens, et al. (2022)
• A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma — I. Raiko, H.P. Rihs, et al. (2017)

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