Clinicopathological correlation of PD-L1 expression in primary and metastatic breast cancer and infiltrating immune cells.

Few studies have evaluated the expression of the programmed cell death-1 and its ligand-1 (PD-L1) in breast cancer. In this study, we correlated differential expression of PD-L1 in breast cancer (BC) and its microenvironment from a cohort of patients with BC, paired locally metastatic disease to regional lymph nodes (LNs) and nonpaired distantly metastatic disease (mets). PD-L1 expression was correlated with several pathologic and clinical parameters in tumor and tumor immune cells (ICs; CD3, CD4, CD8, CD20, and CD68) using the Ventana antibody (SP263) in 41 BCs, 46 paired mets in LNs, and 46 distant mets. There was 100% agreement for PD-L1 expression on tumor and ICs between BC and matched LN. PD-L1 is differentially expressed in primary BC and regional nodal disease. Expression correlated with higher grade, hormone receptor negativity, and highly proliferative tumors (P < .001). In LNs, the high positivity rate was driven by triple-negative status (70% versus 5%; P < .0001). In contrast, there was significantly near-total absence of PD-L1 expression in distant mets compared with BC and LNs (2%-4% in mets versus 17%-20% in BC and LN, P = .009). IC density varied in BC and metastatic tumors with predominance of CD3 and CD68 and near total absence of CD20 cells. PD-L1 expression was mainly associated with CD68 cells. There were consistent higher numbers of CD3 (CD8 > CD4) than CD20 cells in primary and metastatic tumors. Correlation of PD-L1 expression in BC and its microenvironment may be useful for the development of new treatment strategies.

PD-L1 in breast cancer: comparative analysis of 3 different antibodies.

The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.

The utility of IgM, CD21, HGAL and LMO2 in the diagnosis of pediatric follicular lymphoma.

Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular lymphoma arising in adults. Here, we describe a rare case of pFL that showed morphologic features partially overlapping with progressive transformation of germinal centers and reactive follicular hyperplasia. As typical of pFL, neoplastic B cells within follicles did not express B-cell leukemia/lymphoma 2 (BCL2). However, this case showed additional distinctive abnormal findings, which contributed to the diagnosis: (1) diffuse and uniform staining of immunoglobulin M (IgM) on cells within and outside of follicles, (2) abnormally dim expression of CD21 on follicular dendritic cells, and (3) expression of human germinal center-associated lymphoma (HGAL) and LIM domain only 2 (LMO2) on B cells in interfollicular and follicular areas. This case demonstrates the utility of these abnormal features, which can be seen in adult- or usual-type follicular lymphoma, in the diagnosis of pFL. Further studies are necessary to evaluate the significance of these findings in other cases of pFL.