AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 a...AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.Isolated clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.RESULTS:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.The definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.Methylation of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and IMC.Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.CONCLUSION:Cdx2 expression is restored irrespective of the methylation status of its promoter.Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.展开更多
目的研究 HOXC13 mRNA 在成秞细胞瘤(ameloblastoma,AB)中的表达,探讨其发生的意义。方法采用原位杂交法检测47例 AB(原发 AB 29例,复发 AB 14例,恶变 AB 4例),同时选取骨纤维异样增殖症2例,牙源性角化囊性瘤(keratocystic odontogenic ...目的研究 HOXC13 mRNA 在成秞细胞瘤(ameloblastoma,AB)中的表达,探讨其发生的意义。方法采用原位杂交法检测47例 AB(原发 AB 29例,复发 AB 14例,恶变 AB 4例),同时选取骨纤维异样增殖症2例,牙源性角化囊性瘤(keratocystic odontogenic tumor,KCOT)10例,正常口腔黏膜上皮7例作对照。结果 HOXC13 mRNA AB 中阳性率为97.9%(46/47),10例 KCOT 中7例为HOXC13 mRNA 阳性表达,但在7例正常口腔黏膜细胞中仅3例为 HOXC13 mRNA 阳性表达,AB、KCOT、正常黏膜三组间差异有统计学意义(X^2=21.665,P=0.001),但角化及颗粒样变退化细胞却为阴性。在部分 AB 间质成纤维细胞质中也有阳性表达,2例骨纤维异常增殖症纤维也为阳性。结论在 AB 中存在 HOXC13的高表达;HOXC13 mRNA 在 AB 上皮中的表达有异质性,该基因可促进上皮的增殖,其丢失可导致上皮细胞的角化和退变。展开更多
基金Supported by Grant-in Aid from Ministry of Education,Sports and Culture (GP Program for Basic Science),Japan
文摘AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.Isolated clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.RESULTS:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.The definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.Methylation of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and IMC.Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.CONCLUSION:Cdx2 expression is restored irrespective of the methylation status of its promoter.Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.
文摘目的研究 HOXC13 mRNA 在成秞细胞瘤(ameloblastoma,AB)中的表达,探讨其发生的意义。方法采用原位杂交法检测47例 AB(原发 AB 29例,复发 AB 14例,恶变 AB 4例),同时选取骨纤维异样增殖症2例,牙源性角化囊性瘤(keratocystic odontogenic tumor,KCOT)10例,正常口腔黏膜上皮7例作对照。结果 HOXC13 mRNA AB 中阳性率为97.9%(46/47),10例 KCOT 中7例为HOXC13 mRNA 阳性表达,但在7例正常口腔黏膜细胞中仅3例为 HOXC13 mRNA 阳性表达,AB、KCOT、正常黏膜三组间差异有统计学意义(X^2=21.665,P=0.001),但角化及颗粒样变退化细胞却为阴性。在部分 AB 间质成纤维细胞质中也有阳性表达,2例骨纤维异常增殖症纤维也为阳性。结论在 AB 中存在 HOXC13的高表达;HOXC13 mRNA 在 AB 上皮中的表达有异质性,该基因可促进上皮的增殖,其丢失可导致上皮细胞的角化和退变。
