Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays

Hum Pathol. 2019 May;87:11-17. doi: 10.1016/j.humpath.2019.02.001. Epub 2019 Feb 20.


Malignant mesothelioma (MM) is an aggressive neoplasm with poor prognosis. The Dako PD-L1 22C3 and 28-8 pharmDx assays are approved by the US Food and Drug Administration (FDA) as companion and complementary diagnostics for the anti-PD-1 drugs pembrolizumab and nivolumab, respectively. Data from multiple clinical trials indicate that immunotherapy has antitumor activity in advanced malignant pleural (MPM) and peritoneal mesothelioma (MPeM). However, large studies of PD-L1 expression in MM using the FDA-approved anti-PD-L1 assays are lacking. We stained tissue microarray sections (N = 125; 112 MPM and 13 MPeM) using 2 FDA-approved clinical immunohistochemical makers for PD-L1 expression: Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx. Overall, 22% (27/125) of MMs were positive using the 22C3 assay, whereas 27% (32/117) were positive using the 28-8 assay, using a tumor proportion score cutoff of 1%. Tumor cell PD-L1 expression was strongly correlated with PD-L1 expression on tumor-associated immune cells. No significant difference in PD-L1 expression was observed by patient sex, age, treatment history, pathologic stage, or histologic subtype. However, the proportion of cases positive for PD-L1 expression was higher among MPeM compared to MPM (P = .007 for 22C3 assay; P = .04 for 28-8 assay). PD-L1 is expressed in a substantial proportion of MM cases, as measured by FDA-approved companion assays for widely used immunotherapeutic drugs. PD-L1 expression is particularly prevalent in MPeM. These findings support large clinical studies to further examine PD-L1 as a biomarker for a subset of MM patients that may benefit from immunotherapy.

Keywords: Companion diagnostic; Immunotherapy; PD-1; PD-L1; Peritoneal mesothelioma; Pleural mesothelioma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma / drug therapy
  • Mesothelioma / metabolism*
  • Mesothelioma / mortality
  • Mesothelioma / pathology
  • Mesothelioma, Malignant
  • Middle Aged
  • Nivolumab / therapeutic use
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / metabolism*
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / pathology
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / metabolism*
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / pathology
  • Prognosis
  • Survival Rate
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Nivolumab
  • pembrolizumab