NTRK Fusions in 1113 Solid Tumors in a Single Institution

Abstract

Most NTRK fusions occur at very low frequencies in various common cancers. Recent recommendations on NTRK testing recommend immunohistochemistry (IHC) as the initial test for tumor types with a low frequency of NTRK fusions. This study investigated the accuracy of an IHC assay to detect NTRK fusions and characterize the clinicopathological and molecular features of NTRK-rearranged tumors. This retrospective study was conducted on 1113 solid tumor samples known to harbor no oncogenic driver alterations, including 510 non-small cell lung cancers (NSCLC), 503 colorectal cancers (CRC), and 79 inflammatory myofibroblastic tumors (IMT). Additionally, 21 ALK expression-positive cases were included. TRK expression was evaluated using a pan-Trk IHC assay, and positive cases were validated using NGS. TRK expression was observed in three NSCLCs (0.6%), six CRCs (1.2%), and six IMTs (6%). NTRK fusions were finally detected in two NSCLCs (0.4%), six CRCs (1.2%), and one IMT (1%). In NSCLC and CRC, the majority of NTRK fusions were readily discernible due to diffuse moderate-to-strong cytoplasmic staining on pan-Trk IHC. In IMT, focal weak nuclear staining indicated the presence of NTRK fusion. Therefore, the utility of pan-Trk IHC should be assessed considering that the difference in performance depends on tumor type.

Pan‐TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls

“…Inflammatory myofibroblastic tumours (IMT) have been associated with NTRK rearrangements. In a large series of 100 IMT, pan‐TRK was positive in six (6%) neoplasms (five with weak/moderate cytoplasmic staining and one with moderate nuclear staining) 20 . Of those, only one was found to have an ETV6::NTRK3 rearrangement.…”

“…In a large series of 100 IMT, pan-TRK was positive in six (6%) neoplasms (five with weak/moderate cytoplasmic staining and one with moderate nuclear staining). 20 Of those, only one was found to have an ETV6::NTRK3 rearrangement. Arguably, a tumour in the female genital tract showing an inflammatory myofibroblastic morphology and harbouring a NTRK driver rearrangement should now be classified as an NTRK-rearranged neoplasm.…”