Prognosis of patients with malignant mesothelioma by expression of programmed cell death 1 ligand 1 and mesothelin in a contemporary cohort in Finland

Our plain-English summary of Prognosis of patients with malignant mesothelioma by expression of programmed cell death 1 ligand 1 and mesothelin in a contemporary cohort in Finland, by D. Vizcaya, B. Farahmand, A.O. Walter, et al (Cancer Treatment and Research Communications, 2020).

The study

• Authors: D. Vizcaya, B. Farahmand, A.O. Walter, C. Kneip, K. Jöhrens, M. Tukiainen, A.A. Schmitz
• Journal: Cancer Treatment and Research Communications
• Published: 2020;25:100260
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: We aimed to describe mesothelin (MSLN) and programmed cell death 1 ligand 1 (PD-L1) tumour overexpression amongst patients with malignant mesothelioma (MM), and their associations with survival, amongst a cohort of patients with MM in Finland.

Methods: Between 2004 and 2017, 91 adults with histologically confirmed MM were identified from the Auria Biobank in Finland and followed-up using linked data from electronic health records and national statistics. Biomarker content in tumour cell membranes was determined using automated Immunohistochemistry on histological sections. Stained tumour sections were scored for MSLN and PD-L1 intensity. Adjusted associations between MSLN/PD-L1 co-expression and mortality were evaluated by estimating hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression.

Results: Biomarker overexpression occurred in 52 patients for MSLN and 34 patients for PD-L1 and was associated with tumour histology and certain comorbidities. Fifteen per cent of patients had a tumour that overexpressed both biomarkers; r =-0.244, p-value: 0.02. Compared with MSLN+/PD-L1+ patients, HRs (95% CIs) for death were 4.18 (1.71-10.23) for MSLN-/PD-L1+ patients, 3.03 (1.35-6.77) for MSLN-/PD-L1- patients, and 2.13 (0.97-4.67) for MSLN+/PD-L1- patients.

Conclusions: Both MSLN and PD-L1 markers were independent prognostic indicators in patients with MM. Overexpression of MSLN was associated with longer survival; yet their combined expression gave a better indication of survival. The risk of death was four times higher amongst MSLN-/PD-L1+ patients than in MSLN+/PD-L1+ patients.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

In plain English

This retrospective observational study looked at 91 adults in Finland whose malignant mesothelioma was confirmed by tissue examination. They were identified from the Auria Biobank, diagnosed between 2004 and 2017, and 83 had pleural mesothelioma. Tumour samples were stained for two proteins, mesothelin (MSLN) and PD-L1, and patients were followed through health records and national statistics. MSLN was overexpressed in 52 patients and PD-L1 in 34, and 15 of 91 patients overexpressed both. Eighty-eight patients died during follow-up. After adjustment for confounders, MSLN overexpression was associated with a lower risk of death (hazard ratio 0.53, 95% CI 0.31 to 0.91). Compared with patients whose tumours overexpressed both proteins, adjusted hazard ratios for death were 4.18 (1.71 to 10.23) for MSLN-negative/PD-L1-positive patients, 3.03 (1.35 to 6.77) for patients negative for both, and 2.13 (0.97 to 4.67) for MSLN-positive/PD-L1-negative patients. Asbestos exposure recorded in medical records had an adjusted hazard ratio for death of 1.00 (0.60 to 1.65). The authors concluded that both markers were independent prognostic indicators. They noted that the small sample limited precision and that residual confounding may have occurred.

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: Retrospective observational cohort study using biobank tumour samples linked to electronic health records and national statistics
• Who was studied: 91 adults with histologically confirmed malignant mesothelioma, identified from the Auria Biobank (Turku, Finland), diagnosed between 2004 and 2017 and followed to 31 December 2017; 83 (91%) had pleural mesothelioma
• Exposure: The main factors studied were tumour overexpression of mesothelin (MSLN) and PD-L1, measured by immunohistochemistry. Asbestos exposure was taken from patients' electronic health records and included as a covariate. No fiber types were reported.
• Main results:
  • MSLN was overexpressed in 52 patients and PD-L1 in 34 patients. MSLN and PD-L1 H-scores were inversely correlated (r = -0.244, p = 0.02).
  • Of the 52 MSLN-positive patients, 15 were also PD-L1-positive, so 15 of 91 patients overexpressed both markers. Of the 39 MSLN-negative patients, 20 were PD-L1-negative, so 20 of 91 overexpressed neither.
  • 88 of the 91 patients (97%) died during follow-up.
  • Median survival was 195 days for MSLN-negative patients and 375 days for MSLN-positive patients.
  • After adjustment for confounders including histology, MSLN overexpression was associated with a reduced risk of death (HR 0.53, 95% CI 0.31–0.91).
  • For PD-L1 overexpression, the age- and gender-adjusted HR for death was 1.15 (95% CI 0.73–1.80). In the fully adjusted model it was 0.56 (95% CI 0.32–0.99).
  • Compared with MSLN+/PD-L1+ patients, adjusted HRs for death were 4.18 (1.71–10.23) for MSLN-/PD-L1+ patients, 3.03 (1.35–6.77) for MSLN-/PD-L1- patients, and 2.13 (0.97–4.67) for MSLN+/PD-L1- patients.
  • Compared with epithelioid histology, sarcomatoid histology was associated with a greater likelihood of PD-L1 overexpression (OR 4.95, 95% CI 1.33–18.39). Mixed histology was also associated with it.
  • In the multivariable-adjusted model, the HR for death associated with asbestos exposure recorded in medical records was 1.00 (95% CI 0.60–1.65).
• The authors' conclusion: The authors concluded that both MSLN and PD-L1 were independent prognostic indicators in patients with malignant mesothelioma. They also concluded that MSLN and PD-L1 expression is often not concomitant, possibly driven by histological type, and that further studies are needed to confirm the results.
• Limitations the authors state:
  • The study population came from a specific region of Finland and was slightly younger than mesothelioma patients from Turku in the national cancer registry.
  • The small sample size limited the precision of the estimates.
  • The need for consent and for enough tumour content in samples may have introduced selection bias.
  • No matching or propensity scores were used, and residual confounding from unknown or unmeasured variables may have occurred.
  • The biomarkers could not be assessed over time, because only two patients had two tumour samples taken at different times.
  • Apart from the biomarker measurements, all variables came from secondary data, so data collection quality could not be controlled.

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Malignant Mesothelioma, Mesothelin, PD-L1, Biomarker, Immunohistochemistry, Hazard Ratio, confidence interval.

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