Interobserver variability in the evaluation of mismatch repair protein immunostaining

Interobserver variability in the evaluation of mismatch repair protein immunostaining
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DOI:
10.1016/j.humpath.2010.03.003
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发表时间:
2010-10-01
期刊:
影响因子:
3.3
通讯作者:
Nilbert, Mef
Nilbert, Mef
中科院分区:
医学3区
文献类型:
--
作者:
Klarskov, Louise;Ladelund, Steen;Nilbert, Mef

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近年来,错配修复蛋白的免疫组织化学染色已被许多病理实验室建立为常规分析,目的是识别与遗传性非息肉病性结直肠癌综合征相关的肿瘤。尽管应用广泛,但可靠性数据缺乏。因此,我们评估了6名病理学家、3名经验丰富的胃肠病理学家和3名住院医师之间的观察者间变异性。总共225例免疫组织化学染色的结直肠癌被评估为正常、弱、缺失或不可评估的错配修复蛋白染色。51%的MLH1、61%的PMS2、83%的MSH2和45%的MSH6染色结果完全一致。弱染色是一致性降低的主要原因,而在2%至6%的肿瘤中,报告了与正常和染色丧失相矛盾的评估。尽管经验丰富的病理学家和住院医师达成了相同程度的共识,但观察者之间的差异是相当大的。由于免疫组织化学错配修复蛋白染色的结果用于突变分析的决策,并有助于解释遗传性非息肉病性结直肠癌中未知意义的基因变异,因此确定的观察者间变异性强调了质量评估计划的必要性,包括不同表达模式分类的指南。(C) 2010爱思唯尔公司版权所有。
Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein staining. Full consensus was achieved in 51% of the stainings for MLH1, 61% for PMS2, 83% for MSH2, and 45% for MSH6. Weak stainings were the main cause of reduced consensus, whereas contradictory evaluations with normal as well as loss of staining were reported in 2% to 6% of the tumors. Interobserver variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance in hereditary nonpolyposis colorectal cancer, the interobserver variability identified highlights the need for quality assessment programs, including guidelines for classification of different expression patterns. (C) 2010 Elsevier Inc. All rights reserved.