Immunohistochemical Demonstration of Intestinal‐type Alkaline Phosphatase in Stomach Tumors Induced by N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine in Rats

Abstract

A potyclonal antibody against rat intestinal‐type alkaline phosphatase (I‐ALP) was generated and proven to be applicable immunohistochemically to paraffin‐embedded sections. Expression of I‐ALP in normal tissues, intestinal metaplasia and stomach tumors induced by N‐methyl‐N′‐nitro‐N‐nitroso‐guanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wistar (CrjrWistar) and F344 (F344/DuCrj) animals were given drinking water containing 100/μ/ml of MNNG for 30 weeks and were killed at week 50. Among the 5 strains, stomach adenocarcinomas were found most frequently in the SD case. The susceptibility of rats to induction of stomach carcinoma did not correlate with the development of intestinal metaplasias in each strain. Histochemical staining for mucin demonstrated all stomach tumors (adeno‐matous hyperplasias and well‐differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gland cell and surface mucous cell types), with intestinal‐type tumor cells (goblet cell and intestinal absorptive cell types) being only occasional findings. Immunohistochemically, I‐ALP was strongly positive on the striated cell borders of small intestinal absorptive cells of the villus and on brush borders of epithelial cells of kidney proximal tubules. I‐ALP was also detected in the normal stomach, limited to the striated cell borders of absorptive cells of the upper one‐fourth of intestinal metaplastic glands. I‐ALP may thus be a useful marker for stomach tumor cells of intestinal absorptive cell type, indicative of maturation and differentiation. No stomach tumors consisting mainly of intestinal‐type cells were found, and therefore there was no suggestion of any derivation from intestinal metaplasias.