From Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HMHospitales, CIBERONC, Madrid, Spain (Conde, Lopez-Rios).
Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HMHospitales, Madrid, Spain (Hernandez, Sanchez, Alonso, Martinez).
Arch Pathol Lab Med. 2021 Aug 1;145(8):1031-1040. doi: 10.5858/arpa.2020-0400-RA.
CONTEXT.—: Food and Drug Administration-approved TRK inhibitors with impressive overall response rates are now available for patients with multiple cancer types that harbor NTRK rearrangements, yet the identification of NTRK fusions remains a difficult challenge. These alterations are highly recurrent in extremely rare malignancies or can be detected in exceedingly small subsets of common tumor types. A 2-step approach has been proposed, involving a screening by immunohistochemistry (IHC) followed by a confirmatory method (fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction, or next-generation sequencing) in cases expressing the protein. However, there is no interpretation guide for any of the available IHC clones.
OBJECTIVE.—: To provide a pragmatic update on the use of pan-TRK IHC. Selected examples of the different IHC staining patterns across multiple histologies are shown.
DATA SOURCES.—: Primary literature review with PubMed, combined with personal diagnostic and research experience.
CONCLUSIONS.—: In-depth knowledge of pan-TRK IHC will help pathologists implement a rational approach to the detection of NTRK fusions in human malignancies.
目前，食品和药物管理局批准的 TRK 抑制剂对存在 NTRK 重排的多种癌症类型的患者具有显著的总体反应率，但 NTRK 融合的鉴定仍然是一个具有挑战性的难题。这些改变在非常罕见的恶性肿瘤中高度重现，或者可以在常见肿瘤类型的极小亚组中检测到。已经提出了一种两步法，包括免疫组织化学（IHC）筛选，然后在表达该蛋白的情况下使用荧光原位杂交、逆转录聚合酶链反应或下一代测序进行确认方法。然而，目前还没有任何一种可用的 IHC 克隆的解释指南。
提供 pan-TRK IHC 使用的实用更新。展示了多个组织学中不同 IHC 染色模式的一些示例。
与 PubMed 一起进行的主要文献回顾，结合个人诊断和研究经验。
深入了解 pan-TRK IHC 将有助于病理学家在人类恶性肿瘤中采用合理的方法检测 NTRK 融合。
