Horvath Bela, Singh Prabhdeep, Xie Hao, Thota Prashanthi N, Sun Xingwen, Liu Xiuli
Department of Anatomic Pathology, The Cleveland Clinic, Cleveland, OH, USA.
Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA.
Gastroenterol Rep (Oxf). 2016 Nov;4(4):304-309. doi: 10.1093/gastro/gov045. Epub 2015 Oct 19.
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.
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, α-methylacyl-CoA racemase (AMACR), and cyclin D1. A univariate analysis was used to identify predictors for prevalent and incident neoplasia and advanced neoplasia.
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).
In this study, p53 expression was found to be predictive of prevalent advanced neoplasia and progression to advanced neoplasia in patients with BE-IND.
巴雷特食管（BE）患者发生食管腺癌（EAC）的风险增加；因此他们可能需要定期接受内镜监测。如果上皮变化不能明确归类为发育异常阴性或阳性，则建议诊断为发育异常不确定（IND）。已有多种生物标志物被提议作为一般BE人群肿瘤形成的标志物或预测指标；然而，它们在BE-IND患者中的意义尚不清楚。因此，我们进行了一项回顾性研究，以确定这些生物标志物的表达是否与BE-IND患者的肿瘤形成有关。
我们检索了档案，以确定1992年1月至2007年12月期间诊断的所有BE-IND病例。采用免疫组织化学分析对p53、α-甲基酰基辅酶A消旋酶（AMACR）和细胞周期蛋白D1的表达进行半定量。采用单因素分析确定现患和新发肿瘤以及进展期肿瘤的预测指标。
本研究纳入的103例初诊为BE-IND的患者中，81例（78.6%）在诊断后12个月内接受了随访活检；10例（12.3%）发生肿瘤，其中4例（4.9%）为进展期肿瘤。在79例无现患肿瘤且接受了超过1年随访的患者中，18例（22.8%）发生了肿瘤，其中4例（5.1%）为进展期肿瘤。AMACR和细胞周期蛋白D1的表达水平与现患或新发肿瘤无关；然而，高p53表达（>5%）与监测活检时的现患进展期肿瘤相关（P = 0.04），且与进展为进展期肿瘤的风险增加相关（HR = 12；P = 0.03）。
在本研究中，发现p53表达可预测BE-IND患者的现患进展期肿瘤以及进展为进展期肿瘤。
