GISTs with Gene Fusions: A Clinicopathological, Immunophenotypic, and Molecular Study.

The most common mutations in gastrointestinal stromal tumors (GISTs) are or mutations. Recently, neurotrophic tyrosine receptor kinase () fusions have been reported in GISTs, which increased interest in introducing tropomyosin receptor kinase (TRK) inhibitors as treatments for GISTs with fusions. Hence, we aimed to screen fusions in GISTs; we used fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and immunohistochemistry (IHC) to screen fusions in 46 GISTs and evaluate each method. We further reviewed fusion-positive GISTs from the literature and performed clinical and pathological analyses; two GISTs with an - fusion (5%) were identified, while only one (50%) was positive for Pan-TRK expression. On the other hand, among the six GISTs with Pan-TRK-positive expression, only one (17%) harbored fusion. The literature review revealed the strong consistency between FISH and NGS and the limited value of Pan-TRK IHC in screening fusions in GISTs. In addition, the clinical and pathological analysis showed that GISTs with rearrangement occurred less frequently in the stomach, were more frequently larger in size, and the epithelioid type presented with a higher risk of recurrence. The fusion has been more common than the fusion in GISTs to date; our study identified two - fusions in 46 GISTs. Compared with FISH and IHC, NGS is preferred for screening GISTs, including rearrangements. However, since GISTs with fusions are rare, further studies including more samples and mechanistic investigations should be conducted in the future.