Original ArticlesClaudin-18 as a Marker for Identifying the Stomach and Pancreatobiliary Tract as the Primary Sites of Metastatic AdenocarcinomaLi, Wan-Ting MS*; Jeng, Yung-Ming MD, PhD*; Yang, Ching-Yao MD, PhD†Author Information *Department of Pathology, National Taiwan University Hospital, and Graduate Institute of Pathology, National Taiwan University College of Medicine, National Taiwan University †Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, National Taiwan University, Taipei, Taiwan W.-T. L. and Y.-M. J. contributed equally. Conflicts of Interest and Source of Funding: Supported by the Ministry of Science and Technology, Taiwan, Republic of China (Grant Number 107-2314-B-002-044). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Ching-Yao Yang, MD, PhD, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei 100, Taiwan (e-mail: [email protected]). The American Journal of Surgical Pathology: December 2020 - Volume 44 - Issue 12 - p 1643-1648 doi: 10.1097/PAS.0000000000001583 Buy Metrics Abstract Identification of the primary site of cancer is essential for the treatment of patients with cancer. Numerous immunohistochemical markers have been developed to determine the differentiation of tumor cells and suggest possible primary sites, but markers of gastric and pancreatic adenocarcinomas are still lacking. Claudin-18 is a tight-junction protein uniquely expressed in gastric epithelial cells and has been shown to be expressed in gastric and pancreatic adenocarcinoma. Whether claudin-18 can be used as a marker for identifying the primary site of cancer is still unclear. In this study, we used the immunohistochemical method to stain claudin-18 in tissue arrays containing 575 carcinomas from different anatomic sites and representative sections of 157 metastatic adenocarcinomas. In the group of primary tumors, claudin-18 was frequently expressed in gastric, pancreatic, and pulmonary mucinous adenocarcinomas. Half of cholangiocarcinomas and ovarian mucinous carcinomas and some colorectal and pulmonary adenocarcinomas were also positive for claudin-18. In the metastatic cohort, 15 of 17 (88%) gastric adenocarcinomas, 18 of 23 (78%) pancreatic adenocarcinomas, and 4 of 7 (57%) cholangiocarcinomas and gallbladder adenocarcinomas were positive for claudin-18. Only 4 tumors that originated outside the stomach and pancreatobiliary tract were positive for claudin-18. After normalization to the tumor frequency, the sensitivity of claudin-18 for identifying the stomach and pancreatobiliary tract as primary tumor sites was 79%, and the specificity was 93%. The positive and negative predictive values were 76% and 94%, respectively. In conclusion, claudin-18 represents a sensitive and specific marker for stomach and pancreatobiliary adenocarcinoma that may be a useful diagnostic tool in routine surgical pathology. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.