TEST:

VENTANA pan-TRK (EPR17341) Assay

Pan-TRK IHC has a false-positive rate of ∼4%, particularly in squamous cell carcinomas, underscoring the need for confirmatory NGS to validate IHC findings and assess fusion functionality. Functional NTRK1/2/3 fusions remain exceedingly rare in NSCLC, with a detection rate of 0.03% across our combined cohorts.

However, NTRK gene aberrations are rare, necessitating FISH or next-generation sequencing confirmation for pan-TRK-positive cases to identify candidates for TRK-targeted therapy. Further studies are needed to clarify the biological role of non-fusion-mediated pan-TRK overexpression in meningioma progression.

The false-positive rate was 13.3% in acinic cell carcinoma, histologically similar to secretory carcinoma. Luigi-Oral might be a useful alternative to IHC for screening NTRK fusion-positive rare SGC cases, and advances in digital pathology can facilitate implementation of an AI model in the NTRK screening workflow.

Particularly, the detection sensitivity for NTRK3 fusions was significantly enhanced and reached 95.89 %. This study contributes to clarifying NTRK fusion distribution in patients and validates a standardized, sensitive pan-TRK IHC strategy for clinical screening.

According to our research, this case represents the first reported successful surgical resection of a pediatric scalp tumor with NTRK rearrangement. This finding suggests that clinicians should pay attention to early diagnosis through molecular testing and recognize the feasible value of surgical resection in the treatment of this type of tumor.

Our findings suggest that immunohistochemistry can be used as a screening test, but requires molecular confirmation. Our finding of NTRK3 fusion in squamous cell carcinomas with limited treatment options, suggests that the driver function of this gene may be more effective in this group.

Our work showed a high false positive rate in mesenchymal neoplasms using clone EPR17341. Clone A7H6R demonstrated a higher specificity and therefore could be considered in clinical practice for screening mesenchymal tumors for NTRK1 - 3-rearrangements, eventually leading to less unnecessary reflex testing.

A total of 15 SCB tumors from 9 patients were analyzed, with 4 patients providing paired primary and relapsed tumor samples. The median age at diagnosis was 64 years (range 45-78). Median tumor size was 1.7 cm (range 0.6-9.5 cm).

P=N/A; Trial completion date: Mar 2024 --> Mar 2025

In our experience, the comprehensive screening approach based on morphological and clinical/ molecular inclusion criteria, along with the use of immunohistochemical techniques (pan-TRK antibody), significantly enhances the detection rate of NTRK fusions (5. 8% vs. 0.

Pan-TRK IHC shows some utility as a diagnostic and surrogate marker for NTRK screening however, physiologic or non-specific expression may lead to false-positive results.

No NTRK or ALK translocations or increased copy number/amplification were identified in all eight cases which had fluorescence in situ hybridisation and/or next generation sequencing for NTRK1-3 and ALK available for assessment. None of the cases expressed BRAF-V600E.Although our study is limited, our report is the first to document PanTRK expression in AFH in the absence of identifiable NTRK1-3 gene alterations.