Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker

Abstract

The cDNA microarray gene profile of gastrointestinal stromal tumors (GISTs) revealed that DOG1 (TMEM16A) gene was mostly expressed in these neoplasms. Immunohistochemically, DOG1 protein was found positive in a significant proportion of GISTs. However, normal tissues' expression of DOG1 is not yet completely studied. Our study intended to identify the DOG1 protein expression in normal adult and fetal tissues, in comparison with that of GISTs, using an anti-DOG1 polyclonal serum. Fourteen CD117/CD34-positive GIST cases were tested for DOG1. Tissue samples from autopsies of 15 human fetuses and 11 adults were tested immunohistochemically on simple or double staining with antibodies raised against: DOG1, insulin, glucagon, somatostatin, NK1, PGP9.5, chromogranin A, and synaptophysin. All the tested GISTs were positive for DOG1, with a membranous and cytoplasmic location. The normal tissues showed a distinct positivity for DOG1 only in the endocrine pancreas, in both fetal and adult ones. The other tissues tested showed a weak or negative reaction. The DOG1 staining pattern in the pancreas islets was granular, like that of neuroendocrine markers. The location of DOG1 expression in pancreatic islets was partly similar to neuroendocrine markers chromogranin A, PGP9.5, and synaptophysin. The positive cells were situated centrally, in the vicinity of insulin-bearing cells as seen on double staining. DOG1 positivity in fetal and adult pancreatic islets suggests the strong antibody affinity for neuroendocrine cells. Before making a final conclusion regarding the suitability of DOG1 as a new neuroendocrine marker, a large survey of neuroendocrine lesions must be undertaken, including carcinoid tumors of various sites and pancreatic endocrine tumors. To the best of our knowledge, this particular localization has not been reported yet for DOG1.