Diffuse high intensity PD-L1 staining in thymic epithelial tumors.
BACKGROUND
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 high and the remaining as PD-L1 low.


RESULTS
PD-L1 high 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 high 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 high 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.
*Division of Oncology, Department of Internal Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; †Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA; ‡Department of Pathology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; and §Department of Health and Research Policy, Stanford University School of Medicine, Stanford, CA.
Sukhmani K
SK
Padda
Jonathan W
JW
Riess
Erich J
EJ
Schwartz
Lu
L
Tian
Holbrook E
HE
Kohrt
Joel W
JW
Neal
Robert B
RB
West
Heather A
HA
Wakelee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D013950:Thymus Gland / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor