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Pan-TRK Immunohistochemistry for NTRK Gene Fusion Screening of Solid Tumors

By: Julia Fiederlein
Posted: Tuesday, August 2, 2022

Pan-TRK immunohistochemistry may be applied as a screening tool for NTRK rearrangements, especially in commonly diagnosed solid tumors with a low NTRK gene fusion prevalence, according to Birgit Weynand, MD, PhD, of University Hospitals Leuven, Belgium, and colleagues. The results of this retrospective, multicenter study, which were published in the journal Pathobiology, seem to confirm the previously proposed algorithms for NTRK gene fusion screening in solid tumors.

“In the case of pan-TRK immunoreactivity, regardless of its intensity and tumor cell percentage, subsequent molecular tests are recommended to establish a conclusive diagnosis of NTRK rearrangement,” the investigators added. “We, as well as others, have shown that many different solid tumor types can present with some extent of pan-TRK positivity in the absence of NTRK [gene] fusions.”

Data regarding the pan-TRK immunoreactivity patterns of 2,669 solid tumors, comprising carcinomas, sarcomas, and melanocytic lesions, were retrospectively collected from nine laboratories. The contributing laboratories reported the tumor type, percentage of pan-TRK–positive tumor cells, staining intensity, cytoplasmic, membrane and/or nuclear staining pattern, and NTRK gene fusion status.

Most tumors were pan-TRK–negative (92% vs. 8%). NTRK gene fusions were detected in 10% of the pan-TRK–positive tumors. Cytoplasmic immunoreactivity was most frequently observed, followed by membrane immunoreactivity. Nuclear pan-TRK positivity was the least frequent; however, the investigators noted it was most often (33%) associated with the presence of an NTRK gene fusion.

“Although the retrospective nature of our national study precluded the calculation of the ‘real-world’ sensitivity and specificity, we demonstrated here that pan-TRK immunoreactivity patterns strongly overlap between fusion-positive and fusion-negative cases,” the investigators concluded. “It, therefore, seems a safe approach to keep the current threshold for pan-TRK positivity at [at least] 1% of positive tumor cells, regardless [of] the staining pattern, to warrant additional ‘reflex’ molecular testing.”

Disclosure: For full disclosures of the study authors, visit karger.com.


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