The majority of pancreatic neoplasms are characterized by a generally lethal progress within a short period of time after primary diagnosis and the mortality of patients is expected to increase further. Due to lack of efficient screening programs and moderate response to treatments, novel compounds for treatment are needed. We investigated the CLDN18.2 expression in affected patients as in vitro feasibility study for a potential treatment with the novel antibody IMAB362. Therefore, we analyzed the expression of CLDN18.2 in normal pancreatic tissues (N 5 24), primary lesions (N 5 202), metastases (N 5 84) and intra-individually matched samples (N 5 48) of patients with pancreatic ductal adenocarcinoma (PDAC), neuroendocrine neoplasia (NEN) and acinar cell carcinoma. A standardized method for evaluation by immunohistochemistry was developed. The specific staining was evaluated by two independent raters and analysis of staining intensities (range 0-31) and relative proportions of tumor cells were performed. One hundred three (59.2%) samples of primary PDAC were found positive. The vast majority of positive samples were characterized to highly express CLDN18.2: 54.6% (N 5 95) with staining intensities of 21. NEN were positive in 20% of cases (all 21). Metastases of pancreatic neoplasms were also frequently found positive with comparable high rates (69.4% of lymph node and 65.7% of liver metastases). The rate of CLDN18.2 positivity is high in pancreatic neoplasms whereby the expression is not limited to the primaries but is also maintained upon metastasis. Thus, a considerable number of patients with pancreatic neoplasms would be in principle eligible for a CLDN18.2-targeting approach.Pancreatic ductal adenocarcinoma (PDAC), representing >80% of all pancreatic neoplasms, is the seventh most frequent cancer in Europe and is the fourth most frequent cause of cancer related deaths in the European Union (EU).1-3 The prevalence of pancreatic neoplasms is 1-5/10,000 in both, the EU and the United States. 4,5 In contrast to all major cancers, however, the mortality rate of PDAC is expected to increase further. 6 No effective screening programs for early detection of pancreatic neoplasms are available and patients lack specific clinical symptoms at early stages. Thus, most PDAC patients are diagnosed at an advanced stage of the disease and are not suitable for resection with curative intent. For systemic palliative treatment cytotoxic agents are administered. The majority of patients are treated with gemcitabine, whereas patients with a good performance status undergo polychemotherapy with 5-FU/irinotecan/oxaliplatin (FOLFORINOX).3,7 Chemosensitivity of PDAC is moderate 8 and targeted therapeutics are of high interest. Although various compounds have been tested, only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, received approval by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) for the treatment of patients with metastatic disease in combination with gemcitabine. The ...