Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions
Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions
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DOI：
10.1053/j.gastro.2019.05.014
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发表时间：
2019-09-01
期刊：
影响因子：
29.4
通讯作者：
Mino-Kenudson, Mari
中科院分区：
文献类型：
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作者：
Das, Koushik K.;Geng, Xin;Mino-Kenudson, Mari
背景与目的：虽然胰腺囊性病变（PCLs）经常被偶然发现，但确定其恶性风险是一个挑战。在对胰腺导管内乳头状黏液性肿瘤组织和囊肿液的免疫组织化学和酶联免疫吸附试验（ELISA）分析中，单克隆抗体Das-1以高水平的特异性和敏感性识别出那些有恶性肿瘤风险的人。我们的目的是通过比较临床指南和临床特征来验证Das-1识别高危pcl的能力，使用来自多中心队列的样本。方法：我们从4个三级转诊中心（2010年1月至2017年6月）接受手术的患者中获得169例pcl（90例导管内乳头状粘液性肿瘤，43例粘液性囊性肿瘤和36例非粘液性囊肿）的囊肿液样本。手术样本的组织学结果，独立分析和以盲法集中重新审查，被用作参考标准。高风险的pcl是侵袭性癌、高级别不典型增生或肠型导管内乳头状粘液瘤伴中度不典型增生。用Das-1酶联免疫吸附试验（ELISA）与储存的囊肿液样品平行进行。我们评估了生物标志物的性能，生成曲线下面积值，并使用临床和病理特征进行多变量逻辑回归。结果：Das-1 ELISA检测高危pcl的灵敏度为88%，特异性为99%，准确率为95%，截止光密度值为0.104。在100次重复的10倍交叉验证分析中，Das-1识别高风险pcl的灵敏度为88%，特异性为98%。仙台、福冈和美国胃肠病学协会指南标准确定高危pcl的准确率分别为46%、52%和74%（与das1 ELISA 5 mm相比P < 0.05），主胰管扩张>= 1 cm（比值比为47.9,95%可信区间为2.63-108,P < 0.0012），黄疸（比值比为6.16,95%可信区间为1.08-36.7,P = 0.0397）与高危pcl显著相关。结论：我们验证了带有单克隆抗体Das-1的ELISA检测具有高水平敏感性和特异性的恶性肿瘤风险的pcl的能力。该生物标志物可与临床指南结合使用，以识别有恶性肿瘤风险的患者。
BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA 5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation >= 1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.