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单抗 Das-1 能够准确识别胰腺导管腺癌和高级别胰腺上皮内瘤变。

mAb Das-1 identifies pancreatic ductal adenocarcinoma and high-grade pancreatic intraepithelial neoplasia with high accuracy.

机构信息

Division of Gastroenterology, Washington University, St. Louis, 63110, USA.

Division of Gastroenterology, Washington University, St. Louis, 63110, USA.

出版信息

Hum Pathol. 2021 May;111:36-44. doi: 10.1016/j.humpath.2021.01.003. Epub 2021 Jan 30.

Abstract

Pancreatic intraepithelial neoplasia (PanIN) is a microscopic precursor lesion to pancreatic ductal adenocarcinoma (PDAC); however, there are few biomarkers that segregate high-grade PanIN/PDAC from low-grade PanIN lesions. mAb Das-1 is a monoclonal antibody against a colonic epithelial antigen that is reactive to premalignant conditions of the upper gastrointestinal tract including Barrett's esophagus, incomplete-type gastric intestinal metaplasia, and intraductal papillary mucinous neoplasm of the pancreas at high risk of malignancy. We sought to examine a role for Das-1 expression in differentiating high-grade PanIN/PDAC from low-grade PanIN lesions. We examined surgical specimens from 86 patients and 2 autopsied pancreata (74 with and 14 without PDAC) with 107 distinct PanIN lesions, 74 PDAC cases, and 32 associated lymph node metastases, with internal controls of normal pancreatic ducts observed in 56 cases. All of the normal pancreatic duct controls (0/56) and low-grade PanIN (0/95) lesions were nonreactive to Das-1. Das-1 expression among high-grade PanIN (7/12, 58%), PDAC (55/74, 74%), and lymph node metastasis (21/32, 66%) cases was significantly higher (p < 0.0001). Clinicopathologically, Das-1 reactivity was significantly correlated with nodal metastasis (p = 0.021). Overall, the sensitivity, specificity, and accuracy of Das-1 in segregating high-grade PanIN/PDAC from low-grade PanIN lesions and normal ducts were 72%, 100%, and 90%, respectively. Thus, mAb Das-1 reacts with high specificity with high-grade PanIN and PDAC and may help in preoperative diagnosis and/or clinical risk stratification.

摘要

胰腺上皮内瘤变(PanIN)是胰腺导管腺癌(PDAC)的微观前体病变;然而,目前很少有生物标志物能够将高级别 PanIN/PDAC 与低级别 PanIN 病变区分开来。mAb Das-1 是一种针对结肠上皮抗原的单克隆抗体,该抗原对包括巴雷特食管、不完全型胃肠化生和胰腺内导管乳头状黏液性肿瘤在内的上消化道癌前状态具有反应性,这些肿瘤具有较高的恶性潜能。我们试图研究 Das-1 表达在区分高级别 PanIN/PDAC 与低级别 PanIN 病变中的作用。我们检查了 86 名患者和 2 例尸检胰腺(74 例伴和 14 例不伴 PDAC)的手术标本,这些标本中有 107 个不同的 PanIN 病变、74 例 PDAC 病例和 32 例相关的淋巴结转移,其中 56 例观察到正常胰腺导管的内部对照。所有正常胰腺导管对照(0/56)和低级别 PanIN(0/95)病变均对 Das-1 无反应。高级别 PanIN(7/12,58%)、PDAC(55/74,74%)和淋巴结转移(21/32,66%)病例中的 Das-1 表达明显更高(p<0.0001)。临床病理学上,Das-1 反应性与淋巴结转移显著相关(p=0.021)。总的来说,Das-1 在区分高级别 PanIN/PDAC 与低级别 PanIN 病变和正常导管方面的敏感性、特异性和准确性分别为 72%、100%和 90%。因此,mAb Das-1 与高级别 PanIN 和 PDAC 具有高度特异性反应,可能有助于术前诊断和/或临床风险分层。

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