Diffuse high intensity PD-L1 staining in thymic epithelial tumors

Sukhmani K. Padda, Jonathan Riess, Erich J. Schwartz, Lu Tian, Holbrook E. Kohrt, Joel W. Neal, Robert B. West, Heather A. Wakelee

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67 Scopus citations

Abstract

Introduction: Blockade of the immune checkpoint programmed death receptor ligand-1 (PD-L1)/PD-1 pathway has well-established clinical activity across many tumor types. PD-L1 protein expression by immunohistochemistry is emerging as a predictive biomarker of response to these therapies. Here, we examine PD-L1 expression in a thymic epithelial tumor (TET) tissue microarray (TMA). Methods: The TMA contained 69 TETs and 17 thymic controls, with each case represented by triplicate cores. The TMA was stained with rabbit monoclonal antibody (clone 15; Sino Biological, Beijing, China) to human PD-L1. PD-L1 staining was scored based on intensity as follows: 0 = none, 1 = equivocal/uninterpretable, 2 = weak, and 3 = intermediate-strong. Those cases with all cores scoring three in the epithelial component were categorized as PD-L1<sup>high</sup> and the remaining as PD-L1<sup>low</sup>. Results: PD-L1<sup>high</sup> scores were more frequent in TETs than in controls (68.1% versus 17.6%; p = 0.0036). PD-L1 scores and histology were significantly correlated, with higher intensity staining in World Health Organization (WHO). B2/B3/C TETs. Only 14.8% of TETs had PD-L1 staining of associated lymphocytes. In an adjusted analysis (age/sex), PD-L1<sup>high</sup> TETs had a significantly worse overall survival (hazard ratio: 5.40, 95% confidence interval: 1.13-25.89; p = 0.035) and a trend for worse event-free survival (hazard ratio: 2.94, 95% confidence interval: 0.94-9.24; p = 0.064). Conclusions: PD-L1 expression was present in all cases of TETs within the epithelial component but only in a minority in the lymphocytic component. TETs stained more intensely for PD-L1 than in controls, and PD-L1<sup>high</sup> TETs were associated with more aggressive histology and worse prognosis. This study lends rationale to a clinical trial with anti-PD-1/PD-L1 therapy in this rare tumor type.

Original languageEnglish (US)
Pages (from-to)500-508
Number of pages9
JournalJournal of Thoracic Oncology
Volume10
Issue number3
DOIs
StatePublished - Mar 30 2015

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Padda, S. K., Riess, J., Schwartz, E. J., Tian, L., Kohrt, H. E., Neal, J. W., West, R. B., & Wakelee, H. A. (2015). Diffuse high intensity PD-L1 staining in thymic epithelial tumors. Journal of Thoracic Oncology, 10(3), 500-508. https://doi.org/10.1097/JTO.0000000000000429