摘要
Background and aims:Patients with Barrett’s esophagus(BE)are at an increased risk for developing esophageal adenocarcinoma(EAC);thus they may undergo regular endoscopic surveillance.If epithelial changes cannot be unequivocally classified as negative or positive for dysplasia,a diagnosis of indefinite for dysplasia(IND)is recommended.Several biomarkers have been proposed as markers or predictors of neoplasia in the general BE population;however,their significance is not clear in patients with BE-IND.We therefore performed a retrospective study to determine whether expression of these biomarkers was associated with the development of neoplasia in BE-IND patients.Methods:We searched our archives to identify all cases of BE-IND diagnosed between January 1992 and December 2007.Immunohistochemical analyses were used to semi-quantify the expression of p53,a-methylacyl-CoA racemase(AMACR),and cyclin D1.A univariate analysis was used to identify predictors for prevalent and incident neoplasia and advanced neoplasia.Results:Among the 103 patients with an index diagnosis of BE-IND who were included in this study,81(78.6%)underwent a follow-up biopsy within 12 months of diagnosis;10(12.3%)had neoplasia,including four(4.9%)with advanced neoplasia.Among 79 patients without prevalent neoplasia who underwent more than 1 year of follow-up,18(22.8%)had developed neoplasia,including four(5.1%)with advanced neoplasia.AMACR and cyclin D1 expression levels were not correlated with prevalent or incident neoplasia;however,high p53 expression(>5%)was associated with prevalent advanced neoplasia on surveillance biopsy(P=0.04)and with an increased risk of progression to advanced neoplasia(HR=12;P=0.03).Conclusion:In this study,p53 expression was found to be predictive of prevalent advanced neoplasia and progression to advanced neoplasia in patients with BE-IND.
背景与目的:Barrett食管(BE)患者发生食管腺癌的风险增高,因此,需要常规内镜监测。如果上皮改变无法明确界定为阴性或阳性,建议诊断为不确定型上皮改变(IND)。一些生物学标志物被认为可用以预测BE患者的瘤变,但其在BE-IND患者是否具有同样的意义尚不清楚。因此,我们通过回顾性研究来探讨这些生物学标志物是否可以预测BEIND患者的瘤变。方法:收集1992年1月至2007年12月间我中心所有BE-IND患者的临床资料。采用免疫组化分析来对P53、AMACR和cyclin D1的表达进行半定量。对罹患腺瘤/进展型腺瘤(首次随访中发现的病变)和新发腺瘤/进展型腺瘤(首次随访未发现、但在后续随访中发现的病变)的预测因素进行单因素分析。结果:在纳入研究的103例BE-IND患者中,81例(78.6%)在诊断后12月内接受了1次内镜活检,其中10例(12.3%)罹患腺瘤,包括4例(4.9%)进展型腺瘤。在首次随访未发现腺瘤且后续随访超过1年的79例患者中,发现新发腺瘤18例(22.8%),其中4例(5.1%)为进展型腺瘤。AMACR和cyclin D1表达水平与罹患腺瘤或新发腺瘤均无关,但P53高表达(>5%)与罹患进展型腺瘤相关(P=0.04),且可增加后续进展型腺瘤的发生风险(HR=12,P=0.03)。结论:本研究发现P53表达是BE-IND患者罹患及新发进展型腺瘤的预测标志物。
