Immunocytochemical localization of the extracellular calcium-sensing receptor in normal and malignant human large intestinal mucosa

We identified the parathyroid type Ca2+-sensing receptor (CaR) in normal hu man colon mucosa and in cancerous lesions at the mRNA and protein level. Po lymerase chain reaction produced an amplification product from reverse-tran scribed large intestinal RNA which corresponded in size and length to a 537 -bp sequence from exon 7 of the CaR gene. With a specific antiserum against its extracellular domain, the CaR could be detected by immunostaining in n ormal human colon mucosa in cells preferentially located at the crypt base. The CaR protein was also expressed in tumors of the large bowel in all 20 patients examined. However, the great majority of CaR-positive cells in the adenocarcinomas inspected were confined to more differentiated areas exhib iting glandular-tubular structures. Poorly or undifferentiated regions were either devoid of specific immunoreactivity or contained only isolated CaR- positive cells. In the normal mucosa and in glandular-tubular structures of cancerous lesions, the CaR was exclusively expressed in chromogranin A-pos itive enteroendocrine cells and in only a small fraction of PCNA-positive c ells.