TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need...

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Published in:International journal of molecular sciences 2022-12, Vol.23 (23), p.15366
Main Authors: Cappellesso, Rocco, Nicolè, Lorenzo, Del Fiore, Paolo, Barzon, Luisa, Sinigaglia, Alessandro, Riccetti, Silvia, Franco, Renato, Zito Marino, Federica, Munari, Giada, Zamuner, Carolina, Cavallin, Francesco, Sbaraglia, Marta, Galuppini, Francesca, Bassetto, Franco, Alaibac, Mauro, Chiarion-Sileni, Vanna, Piccin, Luisa, Benna, Clara, Fassan, Matteo, Mocellin, Simone, Dei Tos, Angelo Paolo
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Cancer
Carcinoma, Merkel Cell - genetics
Differentiation
EPR17341
Gender
Genes
Humans
Immunohistochemistry
Localization
Medical prognosis
Merkel cell carcinoma
Neoplasms - pathology
Nerve Growth Factors - therapeutic use
Neuroendocrine tumors
NTRK1
NTRK2
NTRK3
Oncogene Proteins, Fusion - genetics
Physiology
Protein-tyrosine kinase receptors
Proteins
Radiation
Receptor, trkA - genetics
Receptor, trkC - genetics
Skin cancer
Skin Neoplasms - genetics
Trk receptors
Tumors
Tyrosine
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Summary:Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need for new treatments. Tumors harboring fusions involving one of the neurotrophin receptor tyrosine kinase ( ) genes are now actionable with targeted inhibitors. -fused genes have been identified in neuroendocrine tumors of other sites; thus, a series of 76 MCCs were firstly analyzed with pan-TRK immunohistochemistry and the positive ones with real-time RT-PCR, RNA-based NGS, and FISH to detect the eventual underlying gene fusion. Despite 34 MCCs showing pan-TRK expression, fusions were not found in any cases. As in other tumors with neural differentiation, TRK expression seems to be physiological and not caused by gene fusions.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms232315366