RESUMO
AIM: To investigate the expression of vascular endothelial growth factor-c (VEGF-C) mRNA and microvessel density (MVD) in human esophageal squamous cell carcinoma (ESCC) and its relationship with clinical significance. METHODS: Specimens obtained from 43 patients undergoing surgical resection for ESCC were used in this study. The expression of VEGF-C mRNA was examined by in situ hybridization. Tumor MVD was determined immunohistochemically with anti-CD31 antibody and estimated by image analysis. Ten sections of adjacent normal mucosa were also examined. RESULTS: VEGF-C mRNA expression was detected in cytoplasm of carcinoma cells. Of the 43 ESCC patients studied, 18 cases (41.9%) were positive for VEGF-C mRNA. No VEGF-C mRNA expression was observed in normal esophageal mucosa. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05). Furthermore, histological grade (differentiation) tended to correlate with VEGF-C mRNA expression, but was not statistically significant (P > 0.05). In tumor lesions, the MVD was significantly greater than that in normal esophageal mucosa. MVD correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P < 0.05), but not with histological grade (differentiation) (P > 0.05). Lesions with VEGF-C mRNA expression had a significantly higher MVD than that of those without VEGF-C mRNA expression (P < 0.05). CONCLUSION: VEGF-C plays a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in ESCC. VEGF-C is one of the important predictors of the biological behavior in ESCC.
Assuntos
Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/irrigação sanguínea , Neoplasias Esofágicas/metabolismo , Neovascularização Patológica/patologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Idoso , Capilares/patologia , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica/fisiopatologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Valor Preditivo dos Testes , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator C de Crescimento do Endotélio Vascular/genéticaRESUMO
AIM: To investigate genetic instability of gene BRCA1 at locus D17S855, and their relationship with clinicopathological characteristics of gastric cancer in Chinese population. METHODS: Microsatellite instability (MSI) and loss of heterozygosity (LOH) of gene BRCA1 at locus D17S855 were compared between 37 samples of gastric cancer and corresponding non-cancerous gastric tissue. RESULTS: MSI at locus D17S855 was positive in 7 of 37 samples of gastric cancer (18.95%). MSI had a close relationship with TNM staging but no relation with lymph node metastasis, histological type or tumor differentiation. MSI positive frequency in TNM I + II (31.58%, 6/19) was much higher than that in TNM III + IV (5.56%, 1/18), (P < 0.05). LOH positive rate was 18.92% (7/37). LOH had no relationship to histological type, tumor differentiation or lymph node metastasis, but LOH positive rate in TNM III + IV was 33.33% (6/18), much higher than that in TNM I + II ( 5.26%, 1/19), (P < 0.05). BRCA1 protein was expressed in 14 of 37 samples of gastric cancer. The positive rates of BRCA1 protein in TNM I + II and TNM III + IV were 57.89% and 16.67%, respectively, (P < 0.05). The positive rate of BRCA1 protein was 77.78% in high differentiation samples, 30.77% in middle differentiation and 12.50% in lower differentiation samples, (P < 0.05). CONCLUSION: MSI of BRCA1 gene could be used as a molecular marker in early phases of sporadic gastric cancer in Chinese population. LOH occurs at later period of gastric cancer, therefore, it could be used as prognostic factor.
Assuntos
Povo Asiático/genética , Genes BRCA1 , Instabilidade Genômica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteína BRCA1/genética , China , DNA de Neoplasias/genética , Progressão da Doença , Genes Neoplásicos/genética , Humanos , Perda de Heterozigosidade/genética , Metástase Linfática/genética , Repetições de Microssatélites/genética , Estadiamento de Neoplasias , Polimorfismo Conformacional de Fita Simples , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etnologiaRESUMO
To investigate microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396, D17S579 and D17S855, and their effect on the expression of nm23H1 and BRCA1 of gastric cancer, which would provide experimental basis for clinical treatment and prognosis analysis of gastric cancer. DNA was extracted from paraffin-embedded materials. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze MSI and LOH. Expression of nm23H, and BRCA1 was detected by Envision immuno-histochemistry and Leica-Qwin computer imaging techniques. In the forty cases of gastric cancer, the frequency of MSI, LOH and nm23H1 protein were 20.00%, 17.50% and 55.00% respectively at locus D17S396, while at locus D17S579, the frequency of MSI, LOH and BRCA1 protein were 22.50%, 15.00% and 37.50% respectively; at locus D17S855, the frequency of MSI, LOH and BRCA1 of thirty-seven cases were 18.92%, 18.92%, 37.84% respectively. In tumor node metastasis (TNM) staging, at locus D17S396, D17S579 and D17S855, MSI in stages I + II appeared more frequently than that in stages III + IV, while LOH appeared the contrary tendency. In the group of metastasis of gastric cancer, MSI had a less frequency (5.00%) than that with no metastasis (35.00%, P < 0.05) at locus D17S396, but LOH appeared more frequently (30.00%) than that with no metastasis (5.00%, P < 0.05). At locus D17S579, MSI had an increasing tendency with the degree of tumor differentiation (50.00% in high differentiation cases, 20.00% in middle differentiation cases, and 0% in low differentiation cases, P < 0.05). The frequency of nm23H1 and BRCA1 protein in stages TNM I + II was higher than that in stages TNM III + IV; and that in higher differentiation cases was higher than in poor differentiation cases. The frequency of nm23H1 protein in the group of metastasis (30.00%) was less than that with no metastasis significantly (80.00%, P<0.01). The frequency of nm23H1 protein in the group positive to MSI (87.50%) was higher than that in the group negative to MSI (46.88%, P < 0.05). However, nm23H1 protein in group positive to LOH (14.29%) was lower than that in the group negative to LOH (63.64%, P < 0.05). The frequency of BRCA1 protein in the group positive to MSI (66.67%) was more than that in the group negative to MSI (29.03%, P < 0.05). The results of experiments indicate that MSI and LOH may separately control the development of sporadic colon cancer with different pathways. MSI may be an early period molecule marker for sporadic colon cancer, enhanced expression of nm23H1 protein can effectively inhibit colon cancer metastasis and improve prognosis of sporadic colon cancer patients. By comparison, LOH mostly arises in the late period of sporadic colon cancer and endows a high aggressive and poor prognostic phenotype. nm23H1 protein could effectively restrain gastric cancer metastasis and development; and BRCA1 protein could restain tumor from becoming lower differentiation.