RESUMO
Exostoses like-3 (EXTL3) is a putative tumour suppressor gene but its involvement in colorectal cancer (CRC) is unclear. We have investigated the role of methylation of the EXTL3 promoter as a mechanism for EXTL3 regulation and tested the hypothesis that loss of EXTL3 expression is associated with mucinous differentiation and alteration of glycoprotein expression in CRC cells. The methylation status of the EXTL3 gene promoter was analysed by methylation-specific PCR following bisulphite modification in CRC cell lines and microdissected primary CRC tissues and their corresponding adjacent normal colorectal mucosa. EXTL3 promoter methylation was detected in seven of 11 mucinous CRCs (63.6%) but in none of 26 non-mucinous CRCs examined. EXTL3 promoter methylation was also detected in the normal colonic mucosa of three patients with mucinous CRC but not in the normal colonic mucosa of any patients with non-mucinous CRC. The presence of EXTL3 methylation was significantly associated with the partial loss of HS expression in mucinous CRC lesions. The mucinous CRC cell lines, Colo201 and Colo205, showed EXTL3 promoter methylation and loss of EXTL3 mRNA expression. However 5-aza-2'-deoxycytidine treatment demethylated the EXTL3 gene promoter and restored its mRNA expression. Furthermore, the basal expression of HS in CRC cells was abolished by treatment with EXTL3-siRNA. We conclude that EXTL3 promoter methylation and its related loss of EXTL3 expression are involved in the loss of HS expression in mucinous CRCs.
Assuntos
Adenocarcinoma Mucinoso/genética , Neoplasias Colorretais/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica/genética , Heparitina Sulfato/genética , N-Acetilglucosaminiltransferases/genética , Proteínas Supressoras de Tumor/genética , Adenocarcinoma Mucinoso/patologia , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Heparitina Sulfato/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases/metabolismo , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/metabolismoRESUMO
The possibility of surgery for aged patients with gastric cancer has been studied. Of 484 cases who underwent a gastrectomy, patients 70 years of age or over amounted to 86 (20%). The postoperative mortality rate for these aged patients was 3% and the postoperative mortality rate with hospital deaths added from other causes than operative deaths was 7%. The postoperative mortality rate of aged patients who underwent total or proximal subtotal gastrectomy improved during the period between 1975-1983 compared with the period between 1967-1974. In the second period, there were no deaths among aged patients who underwent an R3-operation and/or a combine operation. This fact shows that operative procedures have become safer for aged patients.
Assuntos
Neoplasias Gástricas/cirurgia , Adulto , Idoso , Causas de Morte , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Neoplasias Gástricas/mortalidadeRESUMO
The incidence of associated synchronous or heterochronous malignant tumors in this series was 3.3% (21/633). These patients were found more in multiple cancer than single cancer of the stomach. A relatively high incidence of associated cancer of other organs was found with cancer of the large bowel and of the cervix in heterochronous cancer and cancer of the esophagus in synchronous tumors. The cumulative corrected 10-year survival rate of 15 cases of heterochronous tumors was 85.7%. On the other hand, six patients with synchronous tumor had more advanced cancer of other organs than gastric cancer, and four of them died due to cancer of other organs within two years. Both primaries should be found at the early stage and treated with curative surgery and/or radiotherapy.