Spontaneous ECLomas in cotton rats (Sigmodon hispidus): tumours occurring in hypoacidic/hypergastrinaemic animals with normal parietal cells

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas, The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and fo r gene expression by northern blot analysis. Among eight female cotton rats , three had an irregularly thickened oxyntic mucosa, increased stomach weig ht and a high serum gastrin level. Histopathological examination showed ade nomatous hyperplasia of the thickened oxyntic mucosa with areas of an invas ive neoplastic tumour. Immunohistochemistry, using the general neuroendocri ne cell marker chromogranin A (CgA) and the specific ECL cell marker histid ine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia, Parietal cells were not found in the tumour tissue. Parieta l cell density was only slightly reduced in the surrounding oxyntic mucosa, The antral mucosa was histopathologically normal with a normal number of g astrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells di d not show ally differences in the antral and oxyntic mucosa between rats w ith pathological and normal oxyntic mucosa, Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H+/K+ ATPase mRNA was similar in the oxyntic mucosa of those with t hickened and normal oxyntic mucosa, Gastrin mRNA in the antral mucosa was h igh in animals with thickened oxyntic mucosa, Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thic kened oxyntic mucosa, We conclude that the spontaneous gastric carcinoma oc curring in female cotton rats is an ECLoma developing secondary to hypergas trinaemia due to reduced intragastric pH, The mechanism for reduced acidity is not known, but is not gastric atrophy.