Tropomyosin-Related Kinase Receptor and Neurotrophin Expression in Cutaneous Melanoma Is Associated with a Poor Prognosis and Decreased Survival

• Published in: Oncology Vol. 97; no. 1; p. 26
• Main Authors: Antunes, Luís Carlos Moreira, Cartell, André, de Farias, Caroline Brunetto, Bakos, Renato Marchiori, Roesler, Rafael, Schwartsmann, Gilberto
• Format: Journal Article
• Language: English
• Published: Switzerland 01-07-2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Brain-Derived Neurotrophic Factor - genetics; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Melanoma - genetics; Melanoma - immunology; Melanoma - pathology; Melanoma, Cutaneous Malignant; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Middle Aged; Nerve Growth Factor - genetics; Nerve Growth Factors - genetics; Nerve Growth Factors - immunology; Prognosis; Receptor, trkA - genetics; Receptor, trkA - immunology; Receptor, trkB - genetics; Receptor, trkB - immunology; Signal Transduction; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Young Adult; Neurotrophin; TrkB; Brain-derived neurotrophic factor; TrkA; Tropomyosin-related kinase; Melanoma; Nerve growth factor
• ISSN: 1423-0232
• DOI: 10.1159/000499384

Normally, activation of tropomyosin-related kinase (TRK) receptors by neurotrophins (NTs) stimulates intracellular pathways involved in cell survival and proliferation. Dysregulation of NT/TRK signaling may affect neoplasm prognosis. Data on NT and TRK expression in melanomas are limited, and it is unclear whether NT/TRK signaling pathways are involved in the origin and progression of this neoplasm.
We examined whether NT/TRK expression differs across different cutaneous melanoma grades and subtypes, and whether it is associated with melanoma prognosis and survival. A cross-sectional study was performed in which the expression of TrkA, TrkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) was analyzed by immunohistochemistry of 154 melanoma samples. We investigated NT/TRK expression associations with prognostic factors for melanoma, relapse-free survival (RFS), and overall survival (OS).
Of the 154 melanoma samples, 77 (55.4%) were TrkA immunopositive, 81 (58.3%) were TrkB immunopositive, 113 (81.3%) were BDNF immunopositive, and 104 (75.4%) were NGF immunopositive. We found NT/TRK expression associated strongly with several clinical prognostic factors, including the tumor-node-metastasis stage (p < 0.001), histological subtype (p < 0.001), and Clark level (p < 0.05), as well as with a worse OS (p < 0.05 for all, except TrkB) and RFS (p < 0.05 for all).
Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis.