Search

Salivary gland carcinomas (SGCs) are rare and can be subdivided into distinct entities, some of which confer a poor prognosis. As targets for effective systemic therapy are warranted, some studies investigated the role of immune-checkpoint proteins PD-L1 and CTLA-4 in SGC. Our study depicts the expression of lymphocyte activation gene 3 (LAG3) in a test cohort and a larger validation cohort, totaling 139 SGCs. LAG3 is expressed on tumor-infiltrating lymphocytes (TILs), mediates T cell exhaustion and is subject to numerous currently recruiting clinical studies. Overall, one-third of SGCs were infiltrated by LAG3-expressing TILs with a strikingly high concordance between the test cohort and the validation cohort (30% and 28.2%, respectively). In the validation cohort, entity-wise LAG3 expression frequencies were highly variable. The highest rates were observed in salivary duct carcinoma (SDC; 66.7%) and adenocarcinoma not otherwise specified (ANOS; 50.0%). We observed LAG3 expression on effector T cells and in smaller frequencies also on FOXP3- T helper cells and FOXP3+ Tregs. LAG3 expression significantly correlated with advanced nodal metastases, cytotoxic T cell infiltrate and TP53 mutations. In the group of adenoid cystic carcinomas, LAG3 expression was also associated with a shorter event-free survival (EFS). Tumors with TP53 nonsense mutations (TP53 null type) exhibited higher LAG3 frequencies and a shorter EFS compared to TP53 wild type. This is the first report of LAG3 expression in SGC, a promising target for immunotherapy. LAG3 blockage could be distinctly applicable for SDC and ANOS, two SGC types with a particularly poor outcome.

Clinical data confirmed that patients with ROS1 rearrangement are sensitive to specific inhibitors. Therefore, reliable detection of ROS1 rearrangements is essential. Several diagnostic techniques are currently available. However, previous studies were hampered by the low number of ROS1-positive samples. Thirty-five samples, including 32 ROS1 fluorescent in situ hybridization (FISH)-positive and three ROS1 FISH-negative samples were evaluated by ROS1 chromogenic in situ hybridization, ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) immunohistochemistry (IHC), an Agilent SureSelect XT HS custom panel, the Archer FusionPlex Comprehensive Thyroid and Lung panel, and a custom NanoString fusion panel. Some samples were additionally analyzed with the Illumina TruSight Tumor 170 assay. Eleven samples were ROS1 FISH positive by a break-apart signal pattern. In all 11 samples, a ROS1 fusion was confirmed by at least one other method. The other 21 samples tested ROS1 FISH positive by an isolated 3' green signal pattern. Ten of 21 samples could be confirmed by at least two other methods. The other 11 samples tested negative by ROS1 IHC and at least one other method, indicating a false-positive ROS1 FISH result. Our study found that all ROS1 FISH-positive samples with isolated 3' green signals should be confirmed by another method. When sufficient material is available, extraction-based parallel sequencing approaches for the verification of these cases might be preferable., (Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)