RESUMO
OBJECTIVE: MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. METHODS: 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. RESULTS: Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (pâ¯<â¯0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (pâ¯<â¯0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. CONCLUSIONS: The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".
Assuntos
Neoplasias Hipofaríngeas , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/cirurgia , Relevância Clínica , Antígeno Ki-67 , Caderinas/genéticaRESUMO
We investigated the relationship between claudin-1 and micro-lymphatic vessel density (MLVD) by detecting claudin-1 and protein D2-40 expression in cancer tissue specimens obtained from 97 patients with hypopharyngeal squamous cell carcinoma (HSCC). We also explored the correlation between the expression of these proteins and clinical tumor stage, pathological grading, and clinical prognosis in the patients. Moreover, we studied the mechanism of lymph node metastasis in HSCC, thereby providing information for treating HSCC and inhibiting lymph node metastasis. We detected levels of claudin-1 and protein D2-40 expression in cancer tissue from 97 patients with HSCC and para-tumor tissue from 90 patients by immunohistochemistry; we analyzed the correlation between markers and clinicopathological features by using the Pearson chi-square test and conducted survival analysis by the log-rank test. Claudin-1 expression was high in HSCC and was related to tumor differentiation and lymph node metastasis; Kaplan-Meier analysis showed that claudin-1 expression was related to patient survival rate (P = 0.012). There was a significant relationship between MLVD in the tissues adjacent to the carcinoma and the indices of histopathological grade, clinical stage, and lymph node metastasis. There was also a positive correlation between claudin-1 expression and MLVD. High expression of claudin-1 might induce the generation of tumor lymphatic vessels, which increases metastasis in the lymph node. Because claudin-1 is related to patient survival rate, it may be useful as a monitoring index for postoperative HSCC and might be a new target for treating the disease.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Claudina-1/genética , Neoplasias Hipofaríngeas/diagnóstico , Hipofaringe/metabolismo , Vasos Linfáticos/metabolismo , Idoso , Anticorpos Monoclonais Murinos/química , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Claudina-1/metabolismo , Feminino , Expressão Gênica , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/cirurgia , Hipofaringe/patologia , Hipofaringe/cirurgia , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
This study aimed to determine the expression of integrin ß1 and vascular endothelial growth factor (VEGF) and microvascular density (MVD) by CD105 staining in hypopharyngeal squamous cell carcinoma to determine their association with clinicopathologic characteristics, and to determine their role and the effects of their interactions in the development and progression of hypopharyngeal squamous cell carcinomas. The expression of integrin ß1 and VEGF and MVD in hypopharyngeal squamous cell carcinomas and normal hypopharyngeal tissues were evaluated using immunohistochemistry. The Image-Pro Plus software was used to determine the mean optical density of the immunohistochemical images. Integrin ß1 expression was significantly higher in hypopharyngeal squamous cell carcinoma tissues (78.00%) than in normal hypopharyngeal tissues (35.00%; P = 0.001) and significantly differed across pathologic grades and different T stages, and regarding the presence of cervical lymph node metastasis (P < 0.05). VEGF expression was significantly higher in hypopharyngeal squamous cell carcinoma tissues (74.00%) than in normal hypopharyngeal tissues (30.00%; P = 0.002), VEGF overexpression differed significantly across different pathologic grades and different T stages, and regarding the presence of cervical lymph node metastasis (P < 0.05). The MVD count was significantly higher in hypopharyngeal squamous cell carcinoma tissues (37.10 ± 5.95) than in normal hypopharyngeal tissues (8.70 ± 3.34; P = 0.000). MVD differed significantly across different pathologic grades and different T stages, and regarding the presence of cervical lymph node metastasis (P < 0.05). The expression of integrin ß1 and VEGF and the MVD count exhibited no significant differences in terms of age, gender, history of smoking, and clinical stages (P > 0.05). VEGF expression was positively associated with the MVD count of hypopharyngeal squamous cell carcinomas (r = 0.582, P = 0.000); however, integrin ß1 was not associated with VEGF or MVD (P > 0.05). Integrin ß1 and VEGF are overexpressed and MVD increased in hypopharyngeal squamous cell carcinomas. VEGF is positively correlated with MVD.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Hipofaríngeas/genética , Hipofaringe/irrigação sanguínea , Integrina beta1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patologia , Hipofaringe/metabolismo , Hipofaringe/patologia , Integrina beta1/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , Microvasos , Pessoa de Meia-Idade , Gradação de Tumores , Neovascularização Patológica , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Squamous cell carcinoma of the upper aerodigestive tract (UADT) is associated with environmental factors, especially tobacco and alcohol consumption. Genetic factors, including cyclin D1 (CCND1) polymorphism have been suggested to play an important role in tumorigenesis and progression of UADT cancer. To investigate the relationship between CCND1 polymorphism on susceptibility for UADT cancers, 147 cancer and 135 non-cancer subjects were included in this study. CCND1 genotype at codon 242(G870A) in exon 4 was undertaken using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Significant odds ratio (OR) of the AA+GA genotypes [OR=7.5 (95% CI: 1.4-39.7)] was observed in non-drinkers but for non-smokers a non-significant [OR=5.4 (95% CI: 0.9-31.4)] was found in the adjusted model. These results suggest that allele A may be a risk factor for UADT cancer, especially in non-alcoholics. However, further epidemiological studies are needed to establish the exact role of CCND1 polymorphism and the development of UADT cancers.
Assuntos
Carcinoma de Células Escamosas/genética , Ciclina D1/genética , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo Genético/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Genótipo , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Orofaríngeas/genética , Fatores de RiscoRESUMO
OBJECTIVE: To assess alcohol dehydrogenase 3 (ADH3) polymorphism at position Ile349Val as indicator of risk factor for upper aerodigestive tract (UADT) cancer to verify its association with UADT cancer in nonalcoholic or nonsmoking individuals. DESIGN: Cross-sectional study. SETTING: Primary care or referral center. PATIENTS: The study group consisted of 141 consecutive patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx admitted for surgical treatment. The comparison group consisted of 94 inpatients without cancer from the A. C. Camargo or other São Paulo (Brazil) hospital and 40 healthy individuals. INTERVENTION: All participants were interviewed and data were collected using a structured questionnaire. After written informed consent was obtained, 20 mL of blood was collected in heparinized tubes. MAIN OUTCOME MEASURES: Odds ratio for ADH3 genotypes using logistic regression models. RESULTS: After adjustment for sex, age, tobacco use, and history of cancer in first-degree family relatives, a significantly higher odds ratio for UADT cancer was observed among individuals with AA genotype and low cumulative alcohol consumption (< or =100 kg of ethanol) (odds ratio = 3.8 [95% confidence interval, 1.5-9.7]). A 4-fold increase in odds ratio for UADT cancer among individuals with AA genotype and low tobacco consumption (< or =25 pack-years) was also found in the adjusted model. CONCLUSIONS: These results suggest that genotype AA may be a risk factor for UADT cancer, especially in individuals with low alcohol or tobacco consumption. However, further epidemiological case-control or cohort studies, preferably prospective, are needed to establish the exact role of ADH3 polymorphism and its association with the development of UADT cancers.
Assuntos
Álcool Desidrogenase/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Estudos Transversais , Feminino , Genótipo , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Orofaríngeas/genética , Polimorfismo Genético , Fatores de Risco , FumarRESUMO
A carcinogênese é uma alteração do controle do crescimento celular devido a uma exposição prolongada a algum agente com potencial mutagênico. O tabagismo é um importante determinante do risco de câncer de faringe, e a associação com o etilismo aumenta ainda mais este risco. Fatores nutricionais, como na síndrome de Plummer-Vinson, em que há uma anemia ferropriva, parecem ter também importância. Como apenas uma fração dos indíviduos expostos a tabagismo e etilismo desenvolvem câncer, sugere-se que fatores específicos do hospedeiro estabeleçam suscetibilidade diferente. Assim, o sexo masculino é o mais acometido, bem como a sexta e sétima décadas. Encontrou-se um risco relativo maior com a exposição a certas substâncias. Portadores de um primeiro tumor, exposição a radioterapia prévia e aos vírus da papilomatose humana (HPV) e, menos freqüentemente, EBV, apresentam maior risco de desenvolvimento de um câncer faríngeo. Parece ainda haver uma predisposição familiar, bem como uma correlação com a ativação de oncogens e a inativação de gens supressores de tumores, como o p53.