Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status

Our plain-English summary of Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status, by E. Rrapaj, L. Giacometti, P. Spina, et al (Pathology, 2021).

The study

• Authors: E. Rrapaj, L. Giacometti, P. Spina, M. Salvo, G.A. Baselli, C. Veggiani, O. Rena, E. Trisolini, R.L. Boldorini
• Journal: Pathology
• Published: 2021;53(4):462-469
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is often associated with a poor prognosis and options for the treatment of this disease are few. To date, the important role of the immune microenvironment in modifying the disease natural history is well established. The programmed cell death pathway (PD-1/PD-L1) limits the T lymphocyte activation in peripheral tissues when an inflammatory response occurs, and controls the tumour immune escape. PD-L1 is broadly expressed in several malignant tumours and associated with poor clinical outcomes. Thus, the aim of our study is to investigate the potential role of PD-L1 expression in MPM prognosis. Biopsy samples from 198 patients diagnosed with MPM were examined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate PD-L1 protein and gene expression. For PD-L1 protein expression we consider at least 5% membranous staining as positive. Gene expression levels were calculated with ΔΔCt method. Positive expression of PD-L1 by IHC was correlated with worse overall survival (OS; p=0.0225) in MPM patients. PD-L1 positive status was correlated with worse OS in the subgroup of patients with ECOG score <2 (p=0.0004, n=129) and these data were confirmed by multivariate analysis. No significant correlation was found between PD-L1 gene expression and OS. Our results show that PD-L1 evaluated by IHC assay may be a prognostic biomarker for MPM patients with good performance status.

Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

In plain English

This retrospective study from Novara, Italy, examined whether a tumour protein called PD-L1 was linked to survival in 198 patients diagnosed with malignant pleural mesothelioma between 2005 and 2014. The authors stained biopsy samples and counted a tumour as PD-L1 positive if at least 5% of tumour cells showed staining on the cell membrane. By that rule, 24 of 198 (12.12%) were positive. Patients with PD-L1 positive tumours had worse overall survival (p=0.0225). Across the whole cohort, this link was not statistically significant once other factors were taken into account. Among the 129 patients with an ECOG performance-status score below 2 (better general condition), PD-L1 positivity remained linked to worse survival after adjustment (hazard ratio 2.3077, 95% CI 1.264 to 4.212). PD-L1 gene activity, measured in 93 patients, was not significantly linked to survival. Asbestos exposure was recorded as present in 90 of 198 patients (45.5%) and absent in 106, and PD-L1 status was not significantly associated with it. The authors concluded that PD-L1 measured by staining may be a prognostic marker for patients with good performance status.

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 cohort study of archived biopsy samples (immunohistochemistry and RT-PCR), with a supplementary analysis of 86 mesothelioma patients from the public TCGA dataset
• Who was studied: 198 patients diagnosed with malignant pleural mesothelioma between 1 January 2005 and 31 December 2014, biopsied at the Thoracic Surgery Unit of Maggiore della Carità Hospital, Novara, Italy; 133 (67.2%) male; 149 epithelioid, 31 sarcomatoid, 18 biphasic. A separate group of 86 MPM patients came from The Cancer Genome Atlas.
• Exposure: The factor studied was PD-L1 in tumour tissue: protein measured by staining (positive if at least 5% membranous staining) and gene expression measured by RT-PCR. Asbestos exposure was recorded only as yes (90, 45.5%), no (106, 53.5%) or not available (2). No fiber types, jobs or doses were reported.
• Main results:
  • 24 of 198 tumours (12.12%) were PD-L1 positive by staining; 174 (87.87%) were negative
  • Whole cohort: patients with PD-L1 positive tumours had significantly worse overall survival than those with negative tumours (p=0.0225)
  • Subgroup with ECOG score below 2 (129 patients): PD-L1 positivity was linked to worse overall survival (p=0.0004)
  • Multivariate analysis of the whole cohort: PD-L1 positivity was not significantly associated with survival (hazard ratio 1.447, 95% CI 0.912 to 2.297, p=0.117)
  • Multivariate analysis of the ECOG below 2 subgroup (129 patients): PD-L1 positivity was an independent predictor of worse overall survival (hazard ratio 2.3077, 95% CI 1.264 to 4.212, p=0.0064)
  • PD-L1 gene expression (93 patients) showed no significant survival difference between high and low groups (p=0.3828); the same was found in the 86 TCGA patients (p=0.4661)
  • PD-L1 positivity was associated with histological type (p=0.0016): 13 of 49 non-epithelioid versus 11 of 147 epithelioid tumours were positive. It was not significantly associated with age, gender, asbestos exposure, ECOG score, stage, treatment or smoking.
• The authors' conclusion: The authors concluded that PD-L1 levels measured by staining were inversely associated with overall survival. They also concluded that the association held specifically in patients with ECOG score below 2, suggesting PD-L1 as a possible prognostic tissue biomarker for patients with good performance status.
• Limitations the authors state:
  • Gene expression analysis succeeded in only 93 cases (46.97%) because tumour tissue had been used up for diagnostic procedures in the rest

Topics

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

Medical terms in this study, explained in our Lexicon: PD-L1, Prognosis, Pleural Mesothelioma, Performance Status, PD-1/PD-L1, Biopsy, Immunohistochemistry, Overall Survival.

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