RESUMO
BACKGROUND: New blood vessel formation events are essential for tumor clonal expansion and progression. Despite the importance of vascular endothelial growth factor A (VEGFA) for tumor angiogenesis, few studies have evaluated the expression profile of this gene in oral squamous cell carcinoma (OSCC) and tumor margins (TM). This study aimed to evaluate the expression of the VEGFA gene and its protein in OSCC and TM. METHODS: Gene expression was evaluated in cryopreserved samples of OSCCs (n = 44), TM (n = 7), and normal mucosa from healthy patients (n = 3; NM). Quantitative PCRs were performed using the TaqMan system for the VEGFA gene, and gene expression was determined using the 2(-∆∆CQ) method. For immunohistochemical evaluation, 27 OSCC samples were embedded in a tissue microarray (TMA) block and reactions were performed using the Advance system. RESULTS: VEGFA transcript levels were 1.7-fold higher in OSCC than in NM samples. VEGFA mRNA was overexpressed in TM samples compared to NM (3.4-fold) and OSCC (2.0-fold) samples. VEGFA transcript level was overexpressed in T3-T4 tumors, metastatic lymph nodes, and stage III-IV OSCCs. Immunoreactivity of the VEGFA protein was detected in the cytoplasm of parenchymal and stromal cells, mainly in endothelial cells and fibroblasts. CONCLUSION: Our results show that VEGFA was overexpressed in aggressive OSCCs and that VEGFA expression may be an important prognostic factor in this type of cancer. Finally, tumor margins may be involved in the production of angiogenic molecules.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/metabolismo , RNA Mensageiro/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Citoplasma/metabolismo , Progressão da Doença , Expressão Gênica , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias Bucais/irrigação sanguínea , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise Serial de Tecidos , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
BACKGROUND: Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB). METHODS: We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry. RESULTS: We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521). CONCLUSIONS: Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors.