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KMID : 1134120160190030242
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Journal of Breast Cancer
2016 Volume.19 No. 3 p.242 ~ p.251
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Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer
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Bae Sang-Byung
Cho Hyun-Deuk
Oh Mee-Hye
Lee Ji-Hye
Jang Si-Hyong
Hong Soon-Auck
Cho Jun-Hun
Kim Sung-Yong
Han Sun-Wook
Lee Jong-Eun
Kim Han-Jo
Lee Hyun-Ju
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Abstract
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Purpose: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis.
Methods: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas.
Results: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284?4.445; p=0.006) and overall death (HR, 3.666; 95% CI, 1.561?8.607; p=0.003).
Conclusion: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.
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KEYWORD
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Breast neoplasms, PD-L1, Prognosis, Tumor-infiltrating lymphocytes
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