KOC、S100P、间皮素和MUC1在胰胆管腺癌中的表达：一种潜在诊断性免疫组织化学检测组合的开发与应用
Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel.
作者信息
Ali Asif, Brown Victoria, Denley Simon, Jamieson Nigel B, Morton Jennifer P, Nixon Colin, Graham Janet S, Sansom Owen J, Carter C Ross, McKay Colin J, Duthie Fraser R, Oien Karin A
机构信息
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden G61 1QH, UK.
Pathology Laboratory, Forth Valley Royal Hospital, Stirling Road, Larbert FK5 4WR, UK.
出版信息
BMC Clin Pathol. 2014 Jul 23;14:35. doi: 10.1186/1472-6890-14-35. eCollection 2014.
BACKGROUND
Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.
METHODS
Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0-300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.
RESULTS
The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.
CONCLUSION
A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.
背景
胰胆管腺癌（PBA）预后较差。通常通过影像学和/或内镜检查并结合确诊性细胞学检查来进行诊断。细胞学解释可能具有挑战性，尤其是在慢性胰腺炎/胆管炎的情况下。免疫组织化学（IHC）生物标志物可作为细胞学的辅助手段以改善诊断。因此，我们进行了一项荟萃分析，并选择了KOC、S100P、间皮素和MUC1在PBA切除标本中进行进一步验证。
方法
使用来自99例接受手术切除的PBA患者的组织芯片，其中肿瘤芯与正常芯的比例为3:2，用于免疫组织化学检测。在自动化平台上使用针对KOC、S100P、间皮素和MUC1的抗体进行免疫组织化学检测。使用组织芯评分法（范围为0 - 300）对染色强度和染色组织比例进行评分。确定各个生物标志物以及生物标志物组合在不同阳性临界值下的敏感性和特异性，并通过汇总受试者工作特征（ROC）曲线进行比较。
结果
与正常导管相比，所有四种生物标志物在PBA中的表达均较高，KOC的平均组织芯评分分别为150和0.4，S100P为165和0.3，间皮素为115和0.5，MUC1为200和14（所有比较的p < 0.0001）。为敏感性/特异性分析精心选择了五个临界值。其中四个临界值，即5%、10%或20%的阳性细胞以及组织芯评分20，通过ROC曲线分析确定，第五个临界值为中度 - 强染色强度。以20%阳性细胞作为临界值可获得更高的敏感性/特异性值：KOC为84%/100%；S100P为83%/100%；间皮素为88%/92%；MUC1为89%/63%。如果至少2种生物标志物在10%临界值时呈阳性，则KOC、S100P和间皮素组合的分析敏感性为100%，特异性为99%；在20%临界值时敏感性和特异性均为100%。
结论
发现KOC、S100P和间皮素的生物标志物组合，其中至少2种生物标志物呈阳性，在PBA患者的切除标本中，对于10%和20%的临界值而言是最佳组合。
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