Pan-TRK immunohistochemistry as screening tool for NTRK fusions: A diagnostic workflow for the identification of positive patients in clinical practice.
Cancer Biomark
; 38(3): 301-309, 2023.
Article
in En
| MEDLINE
| ID: mdl-37545217
ABSTRACT
BACKGROUND:
Pan-TRK inhibitors Entrectinib and Larotrectinib have been recently approved as tumor-agnostic therapies in NTRK1-2-3 rearranged patients and there is therefore an urgent need to identify reliable and accessible biomarkers for capturing NTRK fusions in the real-world practice.OBJECTIVE:
We aim to assess the analytical validity of the recently released pan-TRK assay (Ventana), running a head-to-head comparison between immunohistochemistry and Archer FusionPlex Lung Panel (ArcherDX) that is designed to detect key fusions in 13 genes, also including NTRK1-3.METHODS:
Pan-TRK IHC and NGS analysis were conducted on a retrospective/prospective cohort of 124 cancer patients (carcinomas, 93 cases; soft tissue sarcomas, 19; primary central nervous system tumours, 10; and neuroblastomas, 2). FISH data were available in most of the IHC/NGS discordant cases.RESULTS:
A comparison between IHC and NGS results was carried out in 117 cases among 30 pan-TRK positive cases, NTRK rearrangement by NGS was found in 11 (37%), while one of the 87 (1.1%) pan-TRK negative cases (a case of NSCLC) showed a TPM3-NRTK1 rearrangement by NGS. Accordingly, sensitivity and specificity of IHC in predicting NTRK status were 91.7% and 81.9%, respectively, while negative (NPV) and positive predictive value (PPV) were 98.8% and 36.7%, respectively.CONCLUSIONS:
These data lead to suggest that IHC with VENTANA pan-TRK antibody can be a reliable screening tool for the identification of patients potentially bearing NTRK rearranged tumours.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lung Neoplasms
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
Cancer Biomark
Journal subject:
BIOQUIMICA
/
NEOPLASIAS
Year:
2023
Document type:
Article
Affiliation country:
Italia