Diagnosis and risk stratification of Barrett's dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue
Diagnosis and risk stratification of Barrett's dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue
复制标题
DOI：
10.1136/gutjnl-2017-313815
复制
发表时间：
2018-07-01
期刊：
影响因子：
24.5
通讯作者：
Kakar, Sanjay
中科院分区：
文献类型：
--
作者：
Choi, Won-Tak;Tsai, Jia-Huei;Kakar, Sanjay
目的Barrett食管（BO）异型增生的诊断具有挑战性，缺乏可靠的辅助技术。本研究使用具有不同程度异型增生的福尔马林固定石蜡包埋（FFPE）BO样本，检查通过流式细胞术检测的DNA含量异常是否可以作为异型增生的诊断标志物，并促进低度异型增生（LGD）和不确定异型增生（IND）患者的风险分层。21例IND和14例非典型增生（ND）阴性。结果HGD组76例（95%），LGD组8例（21.1%），IND组2例（9.5%），ND组0例。DNA含量异常作为HGD诊断指标的敏感性和特异性分别为95%和85%。对于在基线LGD或IND检测到DNA含量异常的患者，随后检测HGD或食管腺癌（OAC）的单变量HR分别为7.0和20.0（p =< 0.001）。结论本研究表明，使用FFPE组织的DNA流式细胞术在BO异型增生的诊断和危险分层中的前景。DNA含量异常的存在与异型增生水平的增加相关，因为95%的HGD样本显示DNA含量异常。DNA流式细胞术还鉴定了LGD和IND患者的一个亚组，这些患者随后检测HGD或OAC的风险较高。
Objective The diagnosis of dysplasia in Barrett's oesophagus (BO) can be challenging, and reliable ancillary techniques are not available. This study examines if DNA content abnormality detected by flow cytometry can serve as a diagnostic marker of dysplasia and facilitate risk stratification of low-grade dysplasia (LGD) and indefinite for dysplasia (IND) patients using formalin-fixed paraffin-embedded (FFPE) BO samples with varying degrees of dysplasia.Design DNA flow cytometry was performed on 80 FFPE BO samples with high-grade dysplasia (HGD), 38 LGD, 21 IND and 14 negative for dysplasia (ND). Three to four 60-micron thick sections were cut from each tissue block, and the area of interest was manually dissected.Results DNA content abnormality was identified in 76 HGD (95%), 8 LGD (21.1%), 2 IND (9.5%) and 0 ND samples. As a diagnostic marker of HGD, the estimated sensitivity and specificity of DNA content abnormality were 95% and 85%, respectively. For patients with DNA content abnormality detected at baseline LGD or IND, the univariate HRs for subsequent detection of HGD or oesophageal adenocarcinoma (OAC) were 7.0 and 20.0, respectively (p =< 0.001).Conclusions This study demonstrates the promise of DNA flow cytometry using FFPE tissue in the diagnosis and risk stratification of dysplasia in BO. The presence of DNA content abnormality correlates with increasing levels of dysplasia, as 95% of HGD samples showed DNA content abnormality. DNA flow cytometry also identifies a subset of patients with LGD and IND who are at higher risk for subsequent detection of HGD or OAC.