Abstract：
Cadherin-17 (CDH17) is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. CDH17 is therefore considered a possible diagnostic and therapeutic target. This study was to comprehensively determine the expression of CDH17 in cancer and to further assess the diagnostic utility of CDH17 immunohistochemistry (IHC). A tissue microarray containing 14,948 interpretable samples from 150 different tumor types and subtypes as well as 76 different normal tissue types was analyzed by IHC. In normal tissues, a membranous CDH17 staining was predominantly seen in the epithelium of the intestine and pancreatic excretory ducts. In tumors, 53 of 150 analyzed categories showed CDH17 positivity including 26 categories with at least one strongly positive case. CDH17 positivity was most common in epithelial and neuroendocrine colorectal neoplasms (50.0%-100%), other gastrointestinal adenocarcinomas (42.7%-61.6%), mucinous ovarian cancer (61.1%), pancreatic acinar cell carcinoma (28.6%), cervical adenocarcinoma (52.6%), bilio-pancreatic adenocarcinomas (40.5-69.8%), and other neuroendocrine neoplasms (5.6%-100%). OnIy 9.9% of 182 pulmonary adenocarcinomas were CDH17 positive. In colorectal adenocarcinomas, reduced CDH17 staining was linked to high pT (p = 0.0147), nodal metastasis (p = 0.0041), V1 (p = 0.0025), L1 (p = 0.0054), location in the right colon (p = 0.0033), and microsatellite instability (p < 0.0001). The CDH17 expression level was unrelated to tumor phenotype in gastric and pancreatic cancer. In summary, our comprehensive overview on CDH17 expression in human tumors identified various tumor entities that might often benefit from anti-CDH17 therapies and suggest utility of CDH17 IHC for the distinction of metastatic gastrointestinal or bilio-pancreatic adenocarcinomas (often positive) from primary pulmonary adenocarcinomas (mostly negative).
摘要：
Cadherin-17(CDH17)是一种主要在肠上皮细胞中表达的膜细胞粘附蛋白。因此,CDH17被认为是可能的诊断和治疗靶标。本研究旨在全面确定CDH17在癌症中的表达，并进一步评估CDH17免疫组织化学（IHC）的诊断实用性。通过IHC分析含有来自150种不同肿瘤类型和亚型以及76种不同正常组织类型的14,948个可解释样品的组织微阵列。在正常组织中,CDH17膜性染色主要见于肠和胰腺排泄管上皮。在肿瘤中，150个分析类别中的53个显示CDH17阳性，包括26个类别，至少有一个强阳性病例。CDH17阳性在上皮和神经内分泌结直肠肿瘤中最常见(50.0%-100%),其他胃肠道腺癌（42.7%-61.6%），粘液性卵巢癌（61.1%），胰腺腺泡细胞癌（28.6%），宫颈腺癌（52.6%），胆胰腺癌（40.5-69.8%），和其他神经内分泌肿瘤（5.6％-100％）。182例肺腺癌中有9.9%为CDH17阳性。在结直肠腺癌中，CDH17染色降低与高pT相关（p=0.0147），淋巴结转移（p=0.0041），V1(p=0.0025),L1（p=0.0054），在右结肠的位置（p=0.0033），和微卫星不稳定性（p<0.0001）。胃癌和胰腺癌中CDH17表达水平与肿瘤表型无关。总之,我们对CDH17在人类肿瘤中的表达进行了全面的概述,确定了可能经常受益于抗CDH17治疗的多种肿瘤实体,并建议使用CDH17IHC区分转移性胃肠道或胆胰腺癌(通常为阳性)和原发性肺腺癌(大多数为阴性).
