Luís Carlos Moreira Antunes1,2, André Cartell3, Caroline Brunetto de Farias4, Renato Marchiori Bakos5,6, Rafael Roesler4,7, Gilberto Schwartsmann5,4,8. 1. Graduate Program in Medical Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil, luisantunes@clinicaviversm.com.br. 2. Hematology and Oncology Service, Santa Maria University Hospital, Federal University of Santa Maria, Santa Maria, Brazil, luisantunes@clinicaviversm.com.br. 3. Department of Pathology, Porto Alegre Clinical Hospital, Porto Alegre, Brazil. 4. Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre Clinical Hospital, Porto Alegre, Brazil. 5. Graduate Program in Medical Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 6. Department of Dermatology, Porto Alegre Clinical Hospital, Porto Alegre, Brazil. 7. Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 8. Department of Internal Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Abstract
OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis.
OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis.
Authors: Timofey D Lebedev; Elmira R Vagapova; Vladimir I Popenko; Olga G Leonova; Pavel V Spirin; Vladimir S Prassolov Journal: Front Oncol Date: 2019-10-18 Impact factor: 6.244
Authors: Vivian P Wagner; Manoela D Martins; Esra Amoura; Virgilio G Zanella; Rafael Roesler; Caroline B de Farias; Colin D Bingle; Pablo A Vargas; Lynne Bingle Journal: Biomedicines Date: 2020-11-24