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

皮肤黑色素瘤中的原肌球蛋白相关激酶受体和神经营养因子表达与预后不良和生存率降低相关

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作者:Luís Carlos Moreira Antunes, André Cartell, Caroline Brunetto de Farias, Renato Marchiori Bakos, Rafael Roesler, Gilberto Schwartsmann

Conclusions

Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis.

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).

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.

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.

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