RET expression in human fetal development

The RET proto-oncogene on chromosome lOql 1.2 is involved in the human hereditary cancer syndromes MEN2A, MEN2B, and FMTC and in Hirschsprung's disease. In embryonic mouse development RETmKNA expression was found in the central and peripheral nervous system, kidney, and liver. Virtually nothing is known about RET expression during human development. As a first step toward understanding the role of RETm human development, we studied the RET protein expression in 14 autopsy cases evenly distributed between 14 weeks of gestation and 9 months postpartum. The organs studied were pancreas, duodenum, ileum, coecum, kidney, bladder, and testis. Immunohistochemistry was performed using a monoclonal antibody to RET in an avidin-biotin-complex system visualized by peroxidase and diaminobenzidine. We found RET expression in acinar pancreatic cells and weak expression in the islet of Langerhans, but not in the ductal cells. The surface epithelial cells of the duodenum, ileum, and coecum had varying levels of HETimmunoreactivity and ganglion cells in the muscle layer and the submucosa were RET reactive. Cells lining the proximal tu-bules in the kidney and cells in the seminiferous tubules of the testis also expressed RET. Finally, the urothelium of the bladder was RETreactive too. We conclude that RET expression is present in epithelial cells of many organs during human development from 14 weeks onward. A possible common denominator is the developmental interaction of epithelial and mesenchymal cells in these organs.