Background Despite well-described analytical effects of autoantibodies against cardiac troponin (cTn) I on experimental assays, no study has systematically examined their impact on cTn assays in clinical use. We determined the effects of endogenous antibodies on 5 different cTnI assays and a cTnT assay. Methods cTn was measured by 6 methods: Siemens hs-cTnI Centaur, Siemens hs-cTnI Vista, Abbott hs-cTnI Architect, Beckman hs-cTnI Access, Beckman cTnI Access, and Roche hs-cTnT Elecsys. Measurements were repeated on 5 assays (all except Siemens hs-cTnI Vista) following immunoglobulin depletion by incubation with protein A. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered positive for macro-cTnI. Protein A findings were validated by gel filtration chromatography and polyethylene glycol precipitation. Results In a sample of 223 specimens selected from a community laboratory that uses the Siemens hs-cTnI Centaur assay and from which cTn was requested, 76% of samples demonstrated increased cTnI (median, 88 ng/L; interquartile range, 62–204 ng/L). Macro-cTnI was observed in 123 (55%) of the 223 specimens. Comparisons of cTnI assays markedly improved once patients with macro-cTnI were removed. Passing-Bablok regression analysis between hs-cTnI assays demonstrated different slopes for patients with and without macro-cTnI. In patients with macro-cTnI, 89 (72%) showed no effect on the recovery of cTnT, whereas 34 (28%) had reduced recovery of cTnT. The proportion of results above the manufacturers' 99th percentile varied with the cTn assay and macro-cTnI status. Conclusion We suggest that the observed discrepancy between hs-cTnI assays may be attributed in part to the presence of macro-cTnI.

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Background: ROS1 gene rearrangements occur in 1-2% of lung adenocarcinomas and define a molecular subgroup susceptible to targeted tyrosine kinase inhibitors. Immunohistochemistry (IHC) for ROS1 can be used to screen for ROS1 rearrangements, but the specificity is not high and confirmation by a molecular method such as fluorescent in situ hybridisation (FISH) is required. Methods: We reviewed lung adenocarcinomas tested for a ROS1 rearrangement by FISH between 2017 and 2019, with the aim to highlight the IHC staining pattern and intensity most likely to correlate with a ROS1 rearrangement. Only cases with evaluable ROS1 IHC and FISH, and with no known EGFR or ALK alterations, were included. Results: Of 123 cases included in the study, 24 (19.51%) were FISH positive and 99 (80.49%) were negative. The ROS1 IHC was assessed for staining intensity (0, 1, 2, or 3+) and % positive cells to generate an H-score (intensity × %). The ROS1 FISH positive cases had a median H-score of 300 (range 200-300; mean 290.83) and negative cases had a median H-score of 20 (range 0-300; mean 46.39). Conclusions: Adenocarcinomas with a FISH-confirmed ROS1 rearrangement demonstrate diffuse, strong (2-3+) IHC staining. Weak, patchy ROS1 IHC staining is not associated with ROS1 rearrangements.

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