NTRK Fusions in 1113 Solid Tumors in a Single Institution
by
, and
Heejin Bang
1
,
Mi-Sook Lee
2,3,
Minjung Sung
2,
Juyoung Choi
2,
Sungbin An
2,3,
Seok-Hyung Kim
4,
Seung Eun Lee
1,* and
Yoon-La Choi
2,3,4,* 1
Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Korea
2
Laboratory of Theranotics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
3
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea
4
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
*
Authors to whom correspondence should be addressed.
Diagnostics 2022, 12(6), 1450; https://doi.org/10.3390/diagnostics12061450
Submission received: 16 May 2022
/
Revised: 9 June 2022
/
Accepted: 9 June 2022
/
Published: 13 June 2022
(This article belongs to the Section Pathology and Molecular Diagnostics)
Simple Summary
Recently, there has been increasing interest in identifying NTRK fusions in various tumors, as they are therapeutically targetable driver mutations. In tumor types with low-frequency NTRK fusions, recent recommendations on NTRK testing recommend pan-Trk immunohistochemistry (IHC) as the initial screening test to validate pan-Trk expression cases with next- generation sequencing (NGS) assays. This retrospective study was conducted on 1113 solid tumor samples (510 non-small cell lung cancers, 503 colorectal cancers, and 100 inflammatory myofibroblastic tumors) to evaluate using pan-Trk IHC assay, and TRK expression cases were followed by validation with NGS. We investigated the accuracy of an IHC assay in detecting NTRK fusions and characterizing the clinicopathological and molecular features of NTRK-rearranged common tumors. Despite its rarity, this study confirms the importance of identifying potential target groups based on the pathological and immunohistochemical characteristics of NTRK fusion-driven solid tumors for effective targeted therapy.
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.
