研究各种阈值作为免疫组织化学观察者一致性的临界值。
Investigating Various Thresholds as Immunohistochemistry Cutoffs for Observer Agreement.
作者信息
Ali Asif, Bell Sarah, Bilsland Alan, Slavin Jill, Lynch Victoria, Elgoweini Maha, Derakhshan Mohammad H, Jamieson Nigel B, Chang David, Brown Victoria, Denley Simon, Orange Clare, McKay Colin, Carter Ross, Oien Karin A, Duthie Fraser R
机构信息
*Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow §Institute of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary ¶Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary ‡Department of Pathology, Laboratory Medicine Building, Queen Elizabeth University Hospital, Greater Glasgow & Clyde NHS ∥West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Alexandra Parade, Glasgow #Pathology Laboratory, Forth Valley Royal Hospital, Larbert, UK †Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
出版信息
Appl Immunohistochem Mol Morphol. 2017 Oct;25(9):599-608. doi: 10.1097/PAI.0000000000000357.
BACKGROUND
Clinical translation of immunohistochemistry (IHC) biomarkers requires reliable and reproducible cutoffs or thresholds for interpretation of immunostaining. Most IHC biomarker research focuses on the clinical relevance (diagnostic, prognostic, or predictive utility) of cutoffs, with less emphasis on observer agreement using these cutoffs. From the literature, we identified 3 commonly used cutoffs of 10% positive epithelial cells, 20% positive epithelial cells, and moderate to strong staining intensity (+2/+3 hereafter) to use for investigating observer agreement.
MATERIALS AND METHODS
A series of 36 images of microarray cores stained for 4 different IHC biomarkers, with variable staining intensity and percentage of positive cells, was used for investigating interobserver and intraobserver agreement. Seven pathologists scored the immunostaining in each image using the 3 cutoffs for positive and negative staining. Kappa (κ) statistic was used to assess the strength of agreement for each cutoff.
RESULTS
The interobserver agreement between all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.64, 0.59, and 0.62, respectively, for 10%, 20%, and +2/+3 cutoffs. A good agreement was observed for experienced pathologists using the 10% cutoff, and their agreement was statistically higher than for junior pathologists (P=0.02). In addition, the mean intraobserver agreement for all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.71, 0.60, and 0.73, respectively, for 10%, 20%, and +2/+3 cutoffs. For all 3 cutoffs, a positive correlation was observed with perceived ease of interpretation (P<0.003). Finally, cytoplasmic-only staining achieved higher agreement using all 3 cutoffs than mixed staining patterns.
CONCLUSIONS
All 3 cutoffs investigated achieve reasonable strength of agreement, modestly decreasing interobserver and intraobserver variability in IHC interpretation. These cutoffs have previously been used in cancer pathology, and this study provides evidence that these cutoffs can be reproducible between practicing pathologists.
背景
免疫组化（IHC）生物标志物的临床转化需要可靠且可重复的临界值或阈值来解释免疫染色结果。大多数IHC生物标志物研究聚焦于临界值的临床相关性（诊断、预后或预测效用），而较少强调使用这些临界值时观察者之间的一致性。从文献中，我们确定了3个常用的临界值，即10%阳性上皮细胞、20%阳性上皮细胞以及中等至强染色强度（以下简称+2/+3），用于研究观察者之间的一致性。
材料与方法
一系列36张微阵列芯块的图像，针对4种不同的IHC生物标志物进行染色，染色强度和阳性细胞百分比各不相同，用于研究观察者间和观察者内的一致性。7名病理学家使用阳性和阴性染色的3个临界值对每张图像的免疫染色进行评分。kappa（κ）统计量用于评估每个临界值的一致性强度。
结果
所有7名病理学家使用这3个临界值时观察者间的一致性相当好，对于10%、20%和+2/+3临界值，平均κ评分分别为0.64、0.59和0.62。经验丰富的病理学家使用10%临界值时观察到良好的一致性，且他们的一致性在统计学上高于初级病理学家（P = 0.02）。此外，所有7名病理学家使用这3个临界值时观察者内的平均一致性相当好，对于10%、20%和+2/+3临界值，平均κ评分分别为0.71、0.60和0.73。对于所有3个临界值，观察到与感知的解释难易程度呈正相关（P < 0.003）。最后，仅细胞质染色在使用所有3个临界值时比混合染色模式达成更高的一致性。
结论
所研究的所有3个临界值均达成了合理的一致性强度，在一定程度上降低了IHC解释中观察者间和观察者内的变异性。这些临界值此前已用于癌症病理学，本研究提供了证据表明这些临界值在执业病理学家之间具有可重复性。
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