Interplay between the magnetic and transport properties in the III-V diluted magnetic semiconductor Ga1-xMnxAs

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Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Simple Summary: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks significant expression of estrogen receptor, progesterone receptor, and HER2. Patients with locally advanced or metastatic TNBC benefit from treatment with atezolizumab, a humanized monoclonal antibody that blocks the PD-L1 protein. Immunohistochemical analysis of the tumor microenvironment is essential to determine the amount of tumor-infiltrating PD-L1-positive immune cells. The PD-L1/SP142 clone is the companion diagnostic for atezolizumab. Here we investigate the degree of interobserver agreement among ten breast pathologists in the assessment of PD-L1/SP142 immunohistochemistry, as well as the assessment of tumor-infiltrating lymphocytes (TILs) in 49 metastatic TNBCs. This multicenter study shows that both PD-L1 assessment and TILs assessment are robust markers at the group level, but the observed interobserver variability likely affects treatment decisions for individual patients. Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains >= 1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive vs. negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs