NTRK1

Definition: NTRK1 (TRKA) is receptor tyrosine kinase (RTKs) protein which play a role in the development and maturation of specific component of the nervous system.

The NTKR1 gene encodes the neurotrophic tyrosine kinase-1 receptor and belongs to a family of nerve growth factor receptors whose ligands include neurotrophins.

Neurotrophins and their receptors play an important role in regulating development of both the central and the peripheral nervous systems.

Pathology

 NTRK1 rearrangements in spitzoid tumors (27776007)

 NTRK1 gene fusions in locally aggressive lipofibromatosis-like neural tumors

• The family of pediatric fibroblastic/myofibroblastic tumors encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities.
• Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy.
• A group of superficial soft tissue tumors occurring in children and young adults, has a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation.
• SOX10 and melanocytic markers were negative in all cases tested.
• In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity.
• 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction.
• Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases.
• Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements.
• In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases.
• Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF.
• These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors. (27259011)

Diagnostic use

 Spitz nevus - Spitz tumor

• Spitz tumors are a group of melanocytic neoplasms with distinct morphological features that tend to affect young individuals. (26873340)
• Spitz tumors harbor diverse genetic alterations, including mutations in HRAS, loss of BAP1, or kinase fusions in ROS1, NTRK1, ALK, BRAF, and RET genes. (26873340)

See also

 NTRKs

• NTRK2

Paywall References

 Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors. Agaram NP, Zhang L, Sung YS, Chen CL, Chung CT, Antonescu CR, Fletcher CD. Am J Surg Pathol. 2016 Oct;40(10):1407-16. doi : 10.1097/PAS.0000000000000675 PMID: 27259011

 Spitz Tumors: Comparison of Histological Features in Relationship to Immunohistochemical Staining for ALK and NTRK1. Kiuru M, Jungbluth A, Kutzner H, Wiesner T, Busam KJ. Int J Surg Pathol. 2016 Feb 12. pii: 1066896916630375. PMID: 26873340

 Expression patterns of Trk-A, Trk-B, GRP78, and p75NRT in olfactory neuroblastoma. Weinreb I, Goldstein D, Irish J, Perez-Ordonez B. Hum Pathol. 2009 Apr 20. PMID: 19386345