Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel.

Q2 Medicine
BMC Clinical Pathology Pub Date : 2014-07-23 eCollection Date: 2014-01-01 DOI:10.1186/1472-6890-14-35
Asif Ali, Victoria Brown, Simon Denley, Nigel B Jamieson, Jennifer P Morton, Colin Nixon, Janet S Graham, Owen J Sansom, C Ross Carter, Colin J McKay, Fraser R Duthie, Karin A Oien
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引用次数: 0

Abstract

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.

Abstract Image

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胰胆管腺癌中 KOC、S100P、间皮素和 MUC1 的表达:潜在诊断性免疫组化面板的开发与应用。
背景:胰胆管腺癌(PBA)预后较差。通常通过影像学和/或内镜检查和细胞学确诊。细胞学解释可能比较困难,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检查的辅助手段,从而提高诊断率。因此,我们进行了一项荟萃分析,并选择 KOC、S100P、间皮素和 MUC1 作为 PBA 切除标本的进一步验证指标:方法:对99例手术切除的PBA患者的组织微阵列进行IHC检测,微阵列中的肿瘤和正常核芯的比例为3:2。在自动平台上使用针对 KOC、S100P、间皮素和 MUC1 的抗体进行 IHC 检测。采用 Histoscore 方法(范围为 0-300)对组织核心的染色强度和组织染色比例进行评分。根据不同的阳性临界值确定单个生物标记物以及生物标记物组合的敏感性和特异性,并通过接收器操作特征曲线(ROC)进行比较:结果:与正常导管相比,PBA 中所有四种生物标志物的表达量都很高,KOC 的平均 Histoscore 值为 150,而正常导管为 0.4;S100P 为 165,而正常导管为 0.3;间皮素为 115,而正常导管为 0.5;MUC1 为 200,而正常导管为 14:KOC、S100P 和间皮素的生物标记物面板中至少有 2 个生物标记物呈阳性,是 PBA 患者切除标本中 10% 和 20% 临界值的最佳面板。
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来源期刊
BMC Clinical Pathology
BMC Clinical Pathology Medicine-Pathology and Forensic Medicine
CiteScore
3.30
自引率
0.00%
发文量
0
期刊介绍: BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.
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