Abstract
A Belgian ring trial for pan-TRK immunohistochemistry (IHC) staining was organised to harmonise pan-TRK IHC staining protocols and interpretation. As a reference method, the VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform was selected. Six samples were selected: 2 negative, 2 fusion positive and 2 samples with wild-type endogenous TRK expression. Each participating laboratory stained the slides using their routine pan-TRK IHC and reported their results. In addition, they were asked to return one TRK-stained slide from each case. The coordinating lab evaluated these slides, compared them with the reference method and scored them. Two clones were used during the ring trial: A7H6R (Cell Signaling) and EPR17341 (Abcam/Ventana). Seven protocols achieved a sufficient performance mark, and three labs were advised to further optimise the protocol. Interpretation of pan-TRK IHC proved to be challenging in cases with physiological TRK expression. In addition, depending on the NTRK fusion partner, the staining can vary strongly in both intensity and staining pattern. Labs using the Ventana ready-to-use system based on the EPR17341 clone and using the recommended protocol settings scored best. However, given some small optimisation, all labs scored well on the technical staining and the succeeding evaluation.
Highlights
The neurotrophic tyrosine receptor kinases (NTRK, or commonly used TRK) are a family of transmembrane tyrosine kinases
Oncogenic fusions involving the kinase domain of the NTRK genes have been identified with high prevalence in certain rare cancers like infantile fibrosarcoma or secretory carcinoma of the breast [3]
Less than 0.31% of colorectal carcinomas are found to be NTRK fusion positive, but rates are substantially higher in the high microsatellite instability (MSI-H) phenotype [13]
Summary
The neurotrophic tyrosine receptor kinases (NTRK, or commonly used TRK) are a family of transmembrane tyrosine kinases. Oncogenic fusions involving the kinase domain of the NTRK genes have been identified with high prevalence in certain rare cancers like infantile fibrosarcoma or secretory carcinoma of the breast [3]. Department of Pathology, Jessa Hospital, 3500 Hasselt, Belgium. Biobank UZA/UAntwerpen, Antwerp University Hospital (UZA), Edegem, Belgium. NTRK fusions have been identified in a small percentage of common cancers [5, 6], like soft tissue sarcomas [7], gliomas [8] and carcinomas of the lung [9], colon [10] and thyroid [11]. The 5′ region of a partner gene fuses with the 3′ region of an NTRK gene, resulting in ligand-independent receptor activation [14]
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