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巴雷特食管黏膜发育异常检测的组织学评估及免疫组化标志物的应用

Histological assessment & use of immunohistochemical markers for detection of dysplasia in Barrett's esophageal mucosa.

作者信息

Kinra Prateek, Gahlot Gaurav P S, Yadav Rajni, Baloda Vandana, Makharia Govind K, Gupta Siddhartha Datta, Das Prasenjit

机构信息

Departments of Pathology and Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Departments of Pathology and Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Pathol Res Pract. 2018 Jul;214(7):993-999. doi: 10.1016/j.prp.2018.05.006. Epub 2018 May 16.

DOI:10.1016/j.prp.2018.05.006
PMID:29764708
Abstract

BACKGROUND

Histological assessment of dysplasia in Barrett's esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question.

METHODS

In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0-300).

RESULTS

Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI -0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD (P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs.

CONCLUSIONS

A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE.

摘要

背景

巴雷特食管(BE)发育异常的组织学评估存在较高的观察者间差异。因此,使用辅助标志物早期检测BE中的发育异常是一个重要的临床问题。

方法

在这项回顾性研究中,纳入了4年间连续的BE病例(n = 59)。苏木精和伊红染色切片由3名资深合格病理学家独立复查,他们根据维也纳分类系统对发育异常进行分级,并使用Kappa统计分析观察者间的一致性。随后,对以下疾病类别进行了α-甲基酰基辅酶A消旋酶(AMACR)、p53、细胞周期蛋白D1、β-连环蛋白、H2AX和M30免疫组织化学(IHC)染色检查:无发育异常的BE [NFD](45例)、发育异常不明确的BE(IFD)(4例)、低级别发育异常(LGD)(3例)、高级别发育异常(HGD)(2例)和腺癌(5例)。H评分通过将不同等级的染色分布和染色强度的乘积相加计算得出(评分范围为0 - 300)。

结果

在3名病理学家中,总体一致性较差(κ = 0.06;95% CI -0.089至0.145),在区分LGD和IFD方面分歧最大(κ = 0.21)。修订组织学标准后,kappa值提高到0.53。在进行的IHC染色中,p53、β-连环蛋白、H2AX和M30染色在区分IFD和LGD方面具有显著意义(P值分别为:0.04、0.004、0.05和0.04)。尽管AMACR和β-连环蛋白染色在HGD/腺癌中比在其他类别中上调,但其在IFD和LGD之间的表达无统计学差异。

结论

详细的组织学评分系统可能会使BE发育异常的组织学解释更加统一。使用联合的IHC染色组合似乎有助于检测BE中的发育异常,特别是区分BE中的IFD和LGD变化。

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