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

Cancer Treat Res Commun. 2020:25:100260. doi: 10.1016/j.ctarc.2020.100260. Epub 2020 Dec 2.

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.

Keywords: Biomarkers; Disease progression; Mesothelioma; Prognosis; Programmed cell death 1 ligand 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / pharmacology
  • Antigens, Neoplasm / therapeutic use*
  • B7-H1 Antigen / metabolism*
  • Cohort Studies
  • Female
  • Finland
  • GPI-Linked Proteins / pharmacology
  • GPI-Linked Proteins / therapeutic use*
  • Humans
  • Male
  • Mesothelin
  • Mesothelioma, Malignant / drug therapy*
  • Prognosis

Substances

  • Antigens, Neoplasm
  • B7-H1 Antigen
  • GPI-Linked Proteins
  • MSLN protein, human
  • Mesothelin