GAD2 is a highly specific marker for neuroendocrine neoplasms of the pancreas

Abstract

Abstract Introduction/Objective Glutamate decarboxylase 2 (GAD2) is the most important inhibitory neurotransmitter and plays a role in insulin-producing β-cells of pancreatic islets. The limitation of GAD2 expression to normal brain and pancreatic islet cells makes GAD2 a potential immunohistochemical diagnostic marker. Methods/Case Report To evaluate the diagnostic utility of GAD2 immunohistochemistry (IHC), a tissue microarray containing 19,202 samples from 152 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. Data on progesterone receptor (PR) expression were available on 15,232 tumors from a previous study. Results (if a Case Study enter NA) GAD2 positivity occurred in 20 of 152 tumor categories including 5 tumor categories with at least one strongly positive case. GAD2 positivity was most frequent in neuroendocrine carcinomas (58.3%) and neuroendocrine tumors (63.2%) of the pancreas, followed by granular cell tumors (37.0%) and neuroendocrine tumors of the lung (11.1%). GAD2 in <10% of cases occurred in 16 other tumor entities including paraganglioma, medullary thyroid carcinoma, and small cell carcinoma of the urinary bladder. In a cohort of 95 pancreatic and 380 extra-pancreatic neuroendocrine neoplasms, GAD2 had a sensitivity of 64.2% and a specificity 96.3% for pancreatic tumor origin while PR had a sensitivity of 56.8% and a specificity of 92.6%. Conclusion GAD2 IHC is a highly useful diagnostic tool for the identification of pancreatic origin in case of neuroendocrine neoplasms with unknown site of origin. The particular strength of GAD2 is its high specificity for pancreatic origin. For the distinction of a pancreatic tumor origin, both sensitivity and specificity is higher for GAD2 than for PR. The combination of PR and GAD2 further increases sensitivity and specificity.