Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value

Abstract

Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0.001, both). High PD-L1 immunoscore in TILs and high total immunoscore (in tumour cells and TILs) of PD-L1 were correlated with high histologic grade (p = 0.001 and p < 0.001, respectively), absence of lymphovascular invasion (p = 0.012 and p = 0.007, respectively), negative hormone receptor expression (p = 0.044 and p = 0.001, respectively) and high TILs level (p < 0.001, both). High PD-L1 mRNA expression was associated with high TILs level (p < 0.001, both). PD-L1 positivity in tumour cells was associated with better disease-free survival in HR−/HER2+ breast cancer (p = 0.039). PD-L1 expression in tumour cells and TILs are significantly associated with TILs level in HER2-positive breast cancer. PD-L1 expression in tumour cells might be positive prognostic factor in HR−/HER2+ breast cancers.

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old

“…There are not many studies focusing on the expression of PD-L1 on TILs, but the results regarding the relationship between the latter with various clinicopathologic parameters are consistent (39,48,49). Similarly, the results of our study indicated that patients with PDL1IC IBC are most likely to have ER or PR negative carcinomas, large tumor diameter and high Ki67, all of which are established indicators of poor prognosis.…”

Programmed death‐ligand 1 gene expression is a prognostic marker in early breast cancer and provides additional prognostic value to 21‐gene and 70‐gene signatures in estrogen receptor‐positive disease

“…We have previously shown that PD‐L1 gene expression is associated with prolonged DFS and OS (Matikas et al , 2019b). In the present study, we confirm that PD‐L1 gene expression is correlated with improved outcomes, while we also demonstrate a significant correlation between PD‐L1 mRNA and protein expression, helping to clarify currently available inconsistent studies that have reported high (Guo et al , 2016; Kim et al , 2017), moderate, or low protein–mRNA correlation (Ali et al , 2015; Ren et al , 2018). PD‐L1 mRNA can thus be a promising and reliable prognostic marker compared with current IHC methods but with unclear—up until now—clinical validity and utility.…”

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

“…In particular, PD‐L1 expression has been positively and independently associated with DFS/RFS and/or OS in several unselected primary BC cohorts . In addition, when considering specific BC subtypes, it has been suggested that PD‐L1 protein expression may retain a positive prognostic role in TNBC and in HER2+ BC, in both trastuzumab‐treated and untreated patients .…”