免疫组织化学
组织微阵列
肺癌
医学
病理
ROS1型
癌症研究
融合基因
染色
trk受体
克隆(Java方法)
癌症
生物
受体
内科学
基因
腺癌
神经营养素
遗传学
作者
Hedvig Elfving,Erika Broström,Lotte Moens,Jonas Carlsson Almlöf,Dijana Cerjan,Gilbert Lauter,Helena Nord,Johanna Sofia Margareta Mattsson,Gustav Ullenhag,Carina Strell,Max Backman,Linnéa La Fleur,Hans Brunnström,Johan Botling,Patrick Micke
出处
期刊:Lung Cancer
[Elsevier]
日期:2021-01-01
卷期号:151: 53-59
被引量:17
标识
DOI:10.1016/j.lungcan.2020.11.023
摘要
Abstract
Purpose
The small molecule inhibitors larotrectinib and entrectinib have recently been approved as cancer agnostic drugs in patients with tumours harbouring a rearrangement of the neurotrophic tropomyosin receptor kinase (NTRK). These oncogenic fusions are estimated to occur in 0.1–3 % of non-small cell lung cancers (NSCLC). Although molecular techniques are most reliable for fusion detection, immunohistochemical analysis is considered valuable for screening. Therefore, we evaluated the newly introduced diagnostic immunohistochemical assay (clone EPR17341) on a representative NSCLC cohort. Methods
Cancer tissue from 688 clinically and molecularly extensively annotated NSCLC patients were comprised on tissue microarrays and stained with the pan-TRK antibody clone EPR17341. Positive cases were further analysed with the TruSight Tumor 170 RNA assay (Illumina). Selected cases were also tested with a NanoString NTRK fusion assay. For 199 cases, NTRK RNA expression data were available from previous RNA sequencing analysis. Results
Altogether, staining patterns for 617 NSCLC cases were evaluable. Of these, four cases (0.6 %) demonstrated a strong diffuse cytoplasmic and membranous staining, and seven cases a moderate staining (1.1 %). NanoString or TST170-analysis could not confirm an NTRK fusion in any of the IHC positive cases, or any of the cases with high mRNA levels. In the four cases with strong staining intensity in the tissue microarray, whole section staining revealed marked heterogeneity of NTRK protein expression. Conclusion
The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay will result in a small number of false positive cases. This should be considered when the assay is applied as a screening tool in clinical diagnostics.
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