Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining

Our plain-English summary of Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining, by M.S.I. Mansour, T. Seidal, U. Mager, et al (Cancer Cytopathology, 2017).

The study

• Authors: M.S.I. Mansour, T. Seidal, U. Mager, A. Baigi, K. Dobra, A. Dejmek
• Journal: Cancer Cytopathology
• Published: 2017;125(12):908-917
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant mesothelioma (MM) is an aggressive, fatal tumor. Current therapeutic options only marginally improve survival. Programmed cell death ligand 1 (PD-L1) is a dominant mediator of immunosuppression, binding to programmed cell death 1 (PD-1). PD-L1 is up-regulated in cancer cells, and the PD-1/PD-L1 pathway plays a critical role in tumor immune evasion, thus providing a target for antitumor therapy. Further, a correlation between PD-L1 expression and prognosis has been reported. Studies performed on histological material have revealed expression of PD-L1 in MM, but no study has been performed on MM effusions thus far.

Methods: PD-L1 expression was determined by a commercially available antibody (clone 28-8) in 74 formalin-fixed, paraffin-embedded cell blocks from body effusions obtained at diagnosis from patients with MM. The presence of MM cells was confirmed with CK5/6, calretinin, and EMA and the admixture of macrophages was assessed with CD68. Only cases containing more than 100 tumor cells were assessed. Membranous staining in tumor cells was considered positive. Survival time was calculated from the appearance of the first malignant effusion until death.

Results: Reactivity was observed in 23 of 61 (38%) of cases and was classified as ≥1%-5% (n = 9 cases), >5%-10% (n = 4 cases), >10%-50% (n = 4 cases), and >50% (n = 6 cases) positive cells. Survival times did not differ significantly between patients with PD-L1-positive and PD-L1-negative tumors.

Conclusion: MM effusions are suitable for immune-cytochemical assessment of PD-L1 expression in malignant cells and the results are similar to those reported for histological specimens. Cancer Cytopathol 2017;125:908-17. © 2017 American Cancer Society.

© 2017 American Cancer Society.

In plain English

This laboratory study tested whether PD-L1, a protein that some cancer drugs target, can be measured in fluid drained from body cavities of people with malignant mesothelioma. The authors retrieved archived cell blocks from 74 effusions collected from 1999 through 2016 (69 pleural, 4 peritoneal, 1 pericardial) at two hospitals in Sweden. All samples were taken before therapy. They stained the samples with a commercial PD-L1 antibody (clone 28-8). Thirteen samples were excluded, mostly for too little material, which left 61. PD-L1 was found on at least 1% of tumor cells in 23 of 61 cases (38%), and on more than 50% of tumor cells in 6 of 61. Survival, age and sex did not differ significantly between PD-L1-positive and PD-L1-negative patients at either the 1% or the 50% cutoff. The authors noted a tendency, not statistically significant, toward longer survival with positivity at the 1% threshold. The study did not examine asbestos exposure. The authors concluded that effusions are suitable for PD-L1 testing and that the results are similar to those reported for tissue specimens.

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 laboratory study of archived effusion cytology cell blocks, with survival comparison
• Who was studied: 74 malignant effusions from patients with malignant mesothelioma, collected from 1999 through 2016 (69 pleural, 4 peritoneal, 1 pericardial), diagnosed at Skåne University Hospital, Malmö (48 cases) and Halland Hospital, Halmstad (26 cases), Sweden. All were collected before therapy. 61 cases were analyzed, 47 of them histologically verified.
• Exposure: Not studied. The article reports no asbestos or occupational exposure data. The test examined was PD-L1 immunostaining with antibody clone 28-8.
• Main results:
  • Of 74 cases, 13 were excluded: 11 for too few malignant cells or too little material left in the cell block, and 2 for having fewer than 100 tumor cells. That left 61 cases for analysis.
  • PD-L1 expression (at least 1% of tumor cells) was found in 23 of 61 cases (38%).
  • Among the 23 positive cases, the share of positive tumor cells was 1% to 5% in 9 cases, more than 5% to 10% in 4 cases, more than 10% to 50% in 4 cases, and more than 50% in 6 cases.
  • Survival did not differ significantly between patients with and without PD-L1 expression, at the 1% cutoff (P = .16) or the 50% cutoff (P = .90). Age and sex also showed no significant differences.
  • The authors reported a tendency, not statistically significant, toward longer survival with PD-L1 positivity at the 1% threshold.
  • At the 1% positivity level, the examiners' scores agreed in 52 of the 61 cases.
  • In a preliminary test on 3 benign effusions not included in the study, benign mesothelial cells showed no membranous PD-L1 staining.
• The authors' conclusion: The authors concluded that mesothelioma effusions are suitable for immunocytochemical assessment of PD-L1 expression in malignant cells, and that the results are similar to those reported for histological specimens.
• Limitations the authors state:
  • Some effusions could not be assessed because there was too little material or too few malignant cells.
  • Samples containing a mix of macrophages and fewer, dispersed malignant cells were harder to assess.
  • Sarcomatoid mesothelioma was under-represented, because it seldom sheds malignant cells into effusions.
  • No study has tested whether results with this antibody predict therapy response in mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: PD-L1, Mesothelioma, Malignant Mesothelioma, PD-1/PD-L1, Prognosis, Cell Block, Calretinin, Macrophage.

Related studies

• Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study — S. Valmary-Degano, P. Colpart, et al. (2017)
• Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology — J. Andrici, A. Sheen, et al. (2015)
• Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma — S. Inaguma, J. Lasota, et al. (2018)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)
• Shorter Survival in Malignant Pleural Mesothelioma Patients With High PD-L1 Expression Associated With Sarcomatoid or Biphasic Histology Subtype: A Series of 214 Cases From the Bio-MAPS Cohort — S. Brosseau, C. Danel, et al. (2019)
• 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)

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