• The presence of monoallelic APC loss in Apcmin/+ mice did not result in any changes to hormone expression.• In patients with FAP, the loss of one allele of APC led to the expression of guanylin, whereas adenomas and cases with biallelic APC loss did not exhibit hormone expression.• Normal intestinal epithelial cells maintain uroguanylin and guanylin expression despite APC heterozygosity, but this expression is lost only after tumor initiation due to APC LOH. The gene discussed is APC; the disease is adenoma.