Heterogeneity in PD-L1 expression on infiltrating immune cells between the primary and metastatic breast cancers

Abstract

Objective: To investigate the expression difference in PD-L1 on mesenchymal infiltrating immune cells between the primary and metastatic breast cancers, and to explore its relationship with clinicopathological parameters. Methods: All cases of primary breast cancer and their matched metastases diagnosed at the Fourth Hospital of Hebei Medical University between January 2010 and December 2018 were included. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 (SP142) in interstitial infiltrating immune cells, and the expression of ER, PR, HER2 and Ki-67 in primary and matched metastases was detected. Statistical software SPSS 24.00 was used for statistical analysis. Kappa test was used for concordance/agreement analysis and McNemar test for difference analysis. Results: Among the 140 identified primary breast cancers, there were 52 cases with matched lymph node metastasis, 88 cases with distant metastasis, including 35 cases with liver metastasis, 21 cases with lung metastasis, 13 cases with chest wall metastasis, 11 cases with bone metastasis, 6 cases with brain metastasis, 1 case with small intestine metastasis, and 1 case with eyeball metastasis. The overall concordance rate of the PD-L1 expression on mesenchymal immune cells between primary breast cancer and paired metastatic breast cancer was 72.9% (κ=0.441). The concordance rate of PD-L1 expression between primary breast cancers and paired lymph node metastases, and that between primary breast cancers and distant metastases were 75.0% (κ=0.472) and 71.6% (κ=0.472), respectively. The inconcordance rate of interstitial immune cell PD-L1 expression between primary breast cancer and matched lung metastasis was 28.6%(6/21), and the difference was statistically significant (P=0.031). The expression of PD-L1 in mesenchymal immune cells of primary breast cancer was significantly correlated with tumor size, histological grade, vascular invasion, lymph node metastasis, and Ki-67 index (P<0.05). The PD-L1 expression was independently associated with lymph node metastasis (P<0.05), while the expression of PD-L1 in metastatic breast cancer interstitial immune cells was significantly related to the expression of ER (P<0.05). Conclusions: The expression of PD-L1 in the primary breast cancer is moderately concordant with that in paired metastases, but different from that in paired lung metastases. Therefore, the expression of PD-L1 in distant metastasis needs to be re-evaluated to optimize the treatment outcomes of PD-L1 based therapy.