IMMUNOHISTOCHEMICAL DEMONSTRATION OF INTESTINAL-TYPE ALKALINE-PHOSPHATASE IN STOMACH TUMORS INDUCED BY N-METHYL-N'-NITRO-N-NITROSOGUANIDINEIN RATS

A polyclonal antibody against rat intestinal-type alkaline phosphatase (I-ALP) was generated and proven to be applicable immunohistochemical ly to paraffin-embedded sections. Expression of I-ALP in normal tissue s, intestinal metaplasia and stomach tumors induced by N-methyl-N'-nit ro-N-nitroso-guanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wi star (Crj:Wistar) and F344 (F344/DuCrj) animals were given drinking wa ter containing 100 mu g/ml of MNNG for 30 weeks and were killed at wee k 50. Among the 5 strains, stomach adenocarcinomas were found most fre quently in the SD case. The susceptibility of rats to induction of sto mach carcinoma did not correlate with the development of intestinal me taplasias in each strain. Histochemical staining for mucin demonstrate d all stomach tumors (adenomatous hyperplasias and well-differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gla nd cell and surface mucous cell types), with intestinal-type tumor cel ls (goblet cell and intestinal absorptive cell types) being only occas ional 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 tub ules, I-ALP was also detected in the normal stomach, limited to the st riated cell borders of absorptive cells of the upper one-fourth of int estinal metaplastic glands. I-ALP may thus be a useful marker for stom ach tumor cells of intestinal absorptive cell type, indicative of matu ration and differentiation, No stomach tumors consisting mainly of int estinal-type cells were found, and therefore there was no suggestion o f any derivation from intestinal metaplasias.