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Hum Pathol. 2019 Feb 19. pii: S0046-8177(19)30017-6. doi: 10.1016/j.humpath.2019.02.001. [Epub ahead of print]

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

Author information

1
Department of Pathology, University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637. Electronic address: david.chapel@uchospitals.edu.
2
Currently at: Department of Pathology and Laboratory Medicine, University of Kentucky, 800 Rose Street MN 150, Lexington, KY 40506; Department of Pathology, University of Utah, 1950 Circle of Hope, Salt Lake City, UT 84112; ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, 84108.
3
Department of Pathology, University of Utah, 1950 Circle of Hope, Salt Lake City, UT 84112; ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, 84108.
4
Department of Pathology, University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637.

Abstract

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 anti-tumor 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 two 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:

Immunotherapy; PD-L1; Peritoneal Mesothelioma; Pleural Mesothelioma

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