Islet-1 Expression in Human Pancreas and in Pancreatic Endocrine Tumors

Background The LIM homeodomain protein Islet-1 is expressed in developing pancreas in rat and mouse. It is essential for the generation of pancreatic endocrine cells: targeted disruption of the islet-1 gene results in an early arrest of embryonic development with abnormality of the pancreas anlage and complete absence of endocrine cells. Islet-1 expression in normal and neoplastic human pancreas has not yet been evaluated. Aim To evaluate Islet-1 protein expression in developing and adult human pancreas and derived tumors. Methods Normal samples of fetal (12w, 14w, 22w), pediatric (1y, 4y) and adult (25y, 55y), formalin fixed-paraffin embedded pancreatic tissues were evaluated for Islet-1 expression with an immunohistochemical technique. Two different monoclonal antibodies, raised against different epitopes of Islet-1 were utilized. Serial sections were immunostained for general neuroendocrine markers (chromogranin and synaptophysin). In order to evaluate coexpression, double immunostainings for either insulin or glucagon and Islet-1 were performed. A large series of previously characterized pancreatic endocrine tumors (PET), including benign (n=50), borderline (n=29), well differentiated (n=30) and poorly differentiated carcinomas (n=10) and pancreatic ductal adenocarcinomas (n=20) were also immunostained with anti- Islet-1 antibodies. Results Islet-1 was expressed in the nuclei of the majority of pancreatic endocrine cells from the beginning of endocrine differentiation in the fetal pancreas till in the adult life. All insulin and glucagon positive cells coexpressed Islet-1. Its reactivity was confined to the endocrine compartment (insulae and periductal endocrine cells); pancreatic acinar and ductal cells were negative. Both antibodies gave the same pattern of reaction and were equally effective in formalin fixed-paraffin embedded material. No Islet-1 immunoreactivity was observed in the ductal adenocarcinoma cases. Nuclear Islet-1 immunoreactivity was present in 87% of PET cases. Poorly differentiated endocrine carcinomas displayed a significant decrease in Islet-1 immunoreactivity with 70% of negative cases, but no relation with prognosis was observed. Conclusions Islet-1 is expressed in developing and adult human endocrine pancreas, at variance with rodent pancreas where its expression is limited to the embryonic life. These antibodies are useful tools for the study of the complex array of transcription factors involved in endocrine differentiation of human pancreas. Islet-1 can be utilized as a sensitive marker for identifying pancreatic endocrine tumors.


Albarello L

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