RESUMEN
The aim of the present study was to determine the role of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) in lip carcinogenesis, to investigate correlations between these markers with microvessel density (MVD) and clinicopathological aspects. Medical records from 27 cases of actinic cheilitis (AC) and 46 cases of lower lip squamous cell carcinoma (LLSCC) were analysed and submitted to immunohistochemistry. VEGFR1- and VEGFR2-immunostained sections were analysed based on percentage of positive epithelial and inflammatory cells, while CD31 was submitted to quantitative analysis to determine MVD. Different patterns of VGFR1 and VEGFR2 expression were observed between AC and LLSCC. VEGFR1 expression in epithelial and inflammatory cells and VEGFR2 expression in epithelial cells were higher in AC compared to LLSCC (p < 0.05). VEGFR1 expression in epithelial cells was higher in LLSCC compared to AC (p < 0.001). Expression of both receptors was not associated to MVD or clinicopathological aspects. A direct correlation was found between epithelial VEGFR1 and VEGFR2 expression (p = 0.02) and between VEGFR2 epithelial and inflammatory expression (p < 0.001). Our findings indicate that activation of VEGFR1 and VEGFR2 in epithelial and inflammatory cells appears to be an early event in lip carcinogenesis.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias de los Labios/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias de los Labios/patología , Masculino , Microvasos/fisiopatología , Neovascularización Patológica/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
Odontogenic lesions (OL) are an important group of oral and maxillofacial diseases represented by odontogenic cysts, benign, and malignant tumors. The brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling pathway has multiple biological actions and has been identified as an important pathway in the proliferation, invasion, and survival of different epithelial tumors. Its role in the development of OL, however, has so far been unexplored. Our aim was to evaluate the BDNF/TrkB/Akt/p-RPS6 signaling pathway in OL of epithelial origin. This cross-sectional study comprised 3 cases of tooth germs, 25 cases of odontogenic keratocyst (OK), 29 cases of ameloblastoma (Am), and 6 cases of ameloblastic carcinoma. Immunohistochemical staining for BDNF, TrkB, p-Akt, and p-RPS6 was performed. OLs were evaluated according to the pattern of immunohistochemical expression in epithelial cells and by semiquantitative scores that considered the intensity of staining and percentage of positive cells. BDNF stromal expression was also assessed. No significant differences were observed with respect to the percentage of positive cases for all markers. Regarding the immunoreactive scores, BDNF and p-RPS6 expressions were similar in the odontogenic epithelium of all OL. However, TrkB and p-Akt were overexpressed in OK compared with ameloblastic carcinoma. In Am, epithelial BDNF was significantly higher compared with stromal expression. In conclusion, BDNF seems to participate in the development of cystic, benign, and malignant odontogenic epithelium to similar degrees. The acquisition of the invasive or malignant phenotype in odontogenic neoplasms is not associated with alterations in the BDNF/TrkB/Akt/RPS6 axis, which could be implicated in the differentiation process.