Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study

Our plain-English summary of Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study, by S. Valmary-Degano, P. Colpart, L. Villeneuve, et al (European Journal of Surgical Oncology, 2017).

The study

• Authors: S. Valmary-Degano, P. Colpart, L. Villeneuve, F. Monnien, L. M'Hamdi, G. Lang Averous, M. Capovilla, F. Bibeau, M.H. Laverriere, V. Verriele-Beurrier, H. Ben Rejeb, P. Dartigues, J. Hommell-Fontaine, F.N. Gilly, S. Isaac, E. Mery, French RENAPE Network
• Journal: European Journal of Surgical Oncology
• Published: 2017;43(10):1915-1923
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM.

Methods: Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS).

Results: Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS.

Conclusion: E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.

Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

In plain English

This French study looked back at stored tumor samples from 45 patients with epithelioid peritoneal malignant mesothelioma, a cancer of the lining of the abdomen. The patients were diagnosed from 1999 to 2015 within the RENAPE network. The study did not measure asbestos exposure. Pathologists stained the samples with two antibodies, E1L3N and SP142, for PD-L1, a protein the authors call a recent biomarker for guiding treatment. Two pathologists agreed moderately when reading E1L3N. With SP142 they agreed only fairly on tumor cells and poorly on immune cells. After a consensus review, E1L3N marked tumor cells in 14 of 45 cases and immune cells in 7 of 45. SP142 marked tumor cells in 10 of 45 and immune cells in 12 of 45. In most positive cases, few tumor cells were positive. Among 39 patients with clinical data, E1L3N staining of immune cells was linked with longer overall and progression-free survival, both before and after adjustment for other factors. SP142 staining, of either immune or tumor cells, showed no statistically significant association with survival. The authors concluded that E1L3N appeared easier to use and that immune-cell PD-L1 measured with E1L3N was an independent prognostic factor.

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 study of archived tumor samples, comparing two staining antibodies and analysing survival with univariate and multivariate (Cox) methods
• Who was studied: 45 patients with epithelioid peritoneal malignant mesothelioma (22 men, 23 women, median age 63), diagnosed 1999 to 2015 in the French RENAPE network. 39 of them were included in the survival analysis; 6 were excluded for lack of clinical data.
• Exposure: Not asbestos. The study measured PD-L1 protein in tumor cells and immune cells using two antibody clones, E1L3N and SP142. Asbestos is mentioned only in the introduction as a possible cause of peritoneal mesothelioma.
• Main results:
  • Agreement between two pathologists was moderate with E1L3N for both tumor (mesothelial) and immune cells (kappa 0.57 and 0.55). With SP142 it was fair for tumor cells (kappa 0.38) and poor for immune cells (kappa 0).
  • After consensus review, PD-L1 was found on tumor cells in 31.1% (14/45) and on immune cells in 15.6% (7/45) of cases with E1L3N. With SP142 the figures were 22.2% (10/45) for tumor cells and 26.7% (12/45) for immune cells.
  • In most positive cases only 1 to 5% of tumor cells were positive. This applied to 12 of 14 E1L3N-positive cases and 6 of 10 SP142-positive cases.
  • Agreement between the two antibodies was moderate (kappa 0.55 for mesothelial cells, 0.54 for immune cells).
  • Among the 39 patients in the survival analysis, 6 had E1L3N-positive immune cells. This was associated with better progression-free survival (univariate p = 0.02; multivariate hazard ratio 0.166, 95% CI 0.031 to 0.9, p = 0.037). It was also associated with better overall survival (univariate p = 0.03; multivariate hazard ratio 0.085, 95% CI 0.01 to 0.712, p = 0.023), using Table 3 values.
  • E1L3N positivity in tumor cells was not significantly associated with survival (univariate p = 0.18 for PFS, p = 0.55 for OS). SP142 staining of either immune or tumor cells was not a statistically significant prognostic factor.
  • Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (21 of 39 patients in the survival analysis) was independently linked with better progression-free survival (HR 0.396, 95% CI 0.178 to 0.877, p = 0.022). It was also linked with better overall survival (HR 0.328, 95% CI 0.13 to 0.826, p = 0.018).
  • The solid tumor subtype was an independent factor for worse overall survival (Table 3: HR 2.916, 95% CI 1.078 to 7.89, p = 0.035).
• The authors' conclusion: The authors concluded three things. E1L3N appeared easier to use than SP142. A minority of these tumors expressed PD-L1, with only a few positive cells. PD-L1 on immune cells measured with E1L3N was an independent prognostic factor.
• Limitations the authors state:
  • The authors note that low staining and low pathologist agreement underline the need for representative samples to avoid false-negative results.
  • The authors state that whether PD-L1 staining predicts response to anti-PD-L1 treatment in these tumors still needs to be investigated. This study did not examine treatment response.

Topics

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

Medical terms in this study, explained in our Lexicon: PD-L1, Epithelioid, Malignant Mesothelioma, Biomarker, Immunohistochemistry, Multivariate Analysis, Overall Survival, Progression-Free Survival.

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• Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays — D.B. Chapel, R. Stewart, et al. (2019)
• Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Malignant pleural mesothelioma: clinical experience and prognostic value of derived neutrophil-to-lymphocyte ratio and PD-L1 expression — L. Gutierrez-Sainz, P. Cruz, et al. (2021)
• Impressive clinical response to anti-PD-1 therapy in epithelioid mesothelioma with high clonal PD-L1 expression and EML4-ALK rearrangement — G. Bronte, A. Delmonte, et al. (2020)

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