NTRK fusions and Trk proteins: what are they and how to test for them

Weiss, Lawrence M.; Funari, Vincent

doi:10.1016/j.humpath.2021.03.007

Cited by 24 publications

(33 citation statements)

References 54 publications

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“…This causes cellular proliferation and tumorigenesis following uncontrolled downstream pathway activation. TrkA activates the MAPK pathway, TrkB the Ras-ERK, PIK3, and PLC-gamma pathways, and TrkC the PI3/AKT pathway [ 26 ].…”

Section: Molecular Landscape Of Follicular Cell-derived Thyroid Cancermentioning

confidence: 99%

“…NTRK rearrangements can be detected by various molecular techniques, including fluorescence in situ hybridization (FISH), reverse-transcriptase PCR (RT-PCR), next generation sequencing (NGS), and IHC, all with their respective advantages and shortfalls [ 26 ].…”

Section: Molecular Landscape Of Follicular Cell-derived Thyroid Cancermentioning

confidence: 99%

“…Immunostaining against TRK antigens detects increased levels of any of the three Trk proteins, namely, Trk A, Trk B, or Trk C ( Figure 5 b), and can be used as a screening tool, as it helps in cost-cutting; however, it is not acceptable as a stand-alone technique [ 26 ].…”

Section: Immunohistochemical Markersmentioning

confidence: 99%

“…There can be false negative and false positive results. The cut-off to categorize a case as positive, ranges from 1 to 10% [ 26 ]. Normal tissues of the central and peripheral nervous system, vascular smooth muscle, and ganglion cells in the wall of the appendix, serve as positive control [ 26 ].…”

Section: Immunohistochemical Markersmentioning

confidence: 99%

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Emerging Biomarkers in Thyroid Practice and Research

Agarwal

Bychkov

Jung

2021

Cancers

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Thyroid cancer is the most common endocrine malignancy. Recent developments in molecular biological techniques have led to a better understanding of the pathogenesis and clinical behavior of thyroid neoplasms. This has culminated in the updating of thyroid tumor classification, including the re-categorization of existing and introduction of new entities. In this review, we discuss various molecular biomarkers possessing diagnostic, prognostic, predictive and therapeutic roles in thyroid cancer. A comprehensive account of epigenetic dysregulation, including DNA methylation, the function of various microRNAs and long non-coding RNAs, germline mutations determining familial occurrence of medullary and non-medullary thyroid carcinoma, and single nucleotide polymorphisms predisposed to thyroid tumorigenesis has been provided. In addition to novel immunohistochemical markers, including those for neuroendocrine differentiation, and next-generation immunohistochemistry (BRAF V600E, RAS, TRK, and ALK), the relevance of well-established markers, such as Ki-67, in current clinical practice has also been discussed. A tumor microenvironment (PD-L1, CD markers) and its influence in predicting responses to immunotherapy in thyroid cancer and the expanding arena of techniques, including liquid biopsy based on circulating nucleic acids and plasma-derived exosomes as a non-invasive technique for patient management, are also summarized.

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Section: Molecular Landscape Of Follicular Cell-derived Thyroid Cancermentioning

confidence: 99%

Section: Molecular Landscape Of Follicular Cell-derived Thyroid Cancermentioning

confidence: 99%

Section: Immunohistochemical Markersmentioning

confidence: 99%

Section: Immunohistochemical Markersmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Biomarkers in Thyroid Practice and Research

Agarwal

Bychkov

Jung

2021

Cancers

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“…S100 and mammaglobin are usually positive; expression of GCDFP-15 has been debated [18,37,47]. Pan-TRK immunohistochemistry has been suggested as a useful tool to confirm SBC diagnosis, or may be used for the selection of patients eligible for NTRK inhibitor therapy in the metastatic setting [79,89]. The clinical course of SBC is indolent compared to IBC-NST; however, metastatic cases have recently been described [34,37].…”

Section: Secretory Breast Carcinoma With Papillary Growth Patternmentioning

confidence: 99%

Papillary lesions of the breast

et al. 2021

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Papillary lesions of the breast represent a heterogeneous group of lesions including benign papillomas, papillomas with focal epithelial atypia, fully fledged ductal carcinoma in situ (DCIS) or lobular neoplasia, papillary DCIS, encapsulated papillary carcinomas without or with invasion, solid papillary carcinomas, and invasive papillary carcinomas. A micropapillary pattern characterized by lack of fibrous stalks within the papillae is observed in micropapillary DCIS and invasive micropapillary carcinoma. In addition, a variety of other rare breast lesions reveals a papillary architecture such as tall cell carcinoma with reversed polarity (TCCRP) and mucinous cystadenocarcinoma, adenomyoepithelioma, and secretory carcinoma. In addition, benign lesions such as usual ductal hyperplasia, apocrine metaplasia, gynecomastia, and juvenile papillomatosis may show a papillary or micropapillary architecture. Fragments of a benign papilloma in a breast biopsy are considered a lesion of uncertain malignant potential (B3 in the European classification) and excision is mostly recommended. Although the knowledge about molecular pathology of papillary breast lesions has increased, there is not sufficient evidence for diagnostically useful molecular features, yet. The aim of this review is to provide an update on papillary and micropapillary lesions with emphasis on problematic areas for daily diagnostic work including biopsies.

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Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

Kazdal

Hofman

Christopoulos

et al. 2022

Genes Chromosomes & Cancer

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Based on superior efficacy and tolerability, targeted therapy is currently preferred over chemotherapy and/or immunotherapy for actionable gene fusions that occur in late‐stage non‐small cell lung carcinoma (NSCLC). Consequently, current clinical practice guidelines mandate testing for ALK, ROS1, NTRK, and RET gene fusions in all patients with newly diagnosed advanced non‐squamous NSCLC (NS‐NSCLC). Gene fusions can be detected using different approaches, but today RNA next‐generation sequencing (NGS) or combined DNA/RNA NGS is the method of choice. The discovery of other gene fusions (involving, eg, NRG1, NUT, FGFR1, FGFR2, MET, BRAF, EGFR, SMARC fusions) and their partners has increased progressively in recent years, leading to the development of new and promising therapies and mandating the development and implementation of comprehensive detection methods. The purpose of this review is to focus on recent data concerning the main gene fusions identified in NSCLC, followed by the discussion of major challenges in this domain.

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NTRK fusions and Trk proteins: what are they and how to test for them

Cited by 24 publications

References 54 publications

Emerging Biomarkers in Thyroid Practice and Research

Emerging Biomarkers in Thyroid Practice and Research

Papillary lesions of the breast

Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

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