Cytoplasmic and nuclear programmed death ligand 1 expression in peritumoral stromal cells in breast cancer: Prognostic and predictive value.

BACKGROUND: Breast cancer (BC) continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population. One of the promising markers associated with BC progression is programmed death ligand 1 (PD-L1). Previously, we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1 (PDCD1 LG1) and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC. However, the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied. AIM: To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics. METHODS: In a prospective single-center observational study, tumor samples from 148 patients with newly diagnosed BC were examined. The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1. In the tumor samples, the PDCD1 LG1-positive lymphocyte (PDCD1 LG1+ LF) score, presence of nuclear PDCD1 LG1 expression in the LFs, PDCD1 LG1 expression in polymorphic cell infiltrates (PDCD1 LG1+ polymorphic cell infiltrates [PCIs]), and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed. Statistical analyses were performed using Statistica 10.0 software. RESULTS: A PDCD1 LG1+ LF score ≥ 3 was detected more often at stages N0 and N3 than at N1 and N2 (P = 0.03). Moderate and pronounced PDCD1 LG1+ PCIs and the presence of PDCD1 LG1+ fibroblastic stroma were associated with negative estrogen receptor status (P = 0.0008 and P = 0.03, respectively), human epidermal growth factor receptor 2-positive (HER2+) BC (P < 0.00001 and P = 0.0005), and luminal B HER2+, non-luminal HER2+ and triple-negative BC (P < 0.00001 and P = 0.004). The risk of metastasis to regional lymph nodes (RLNs) depend on lymphovascular invasion (LVI) and the PDCD1 LG1+ LF score. In the absence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were absent in 66.6% and 93.9% of patients with BC, respectively. In the presence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were detected in 82.6% and 92.7% of patients with BC, respectively. CONCLUSION: The results indicated that the combined assessment of the PDCD1 LG1+ LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.