Immunohistochemical Studies on EGF Family Growth Factors in Normal and Ulcerated Human Gastric Mucosa
Expression of members of the epidermal growthfactor family, including epidermal growth factor (EGF),transforming growth factor-α (TGF-α),amphiregulin (AR), and Cripto, as well as their putative receptor, epidermal growth factor receptor(EGFR), was studied immunohistochemically in humangastric mucosa to evaluate their possible roles in cellproliferation of normal and regenerative gastric mucosa. We also examined the correlation between cellproliferation and EGFR by double immunohistochemicalstaining for proliferating cell nuclear antigen (PCNA)and EGFR. In normal gastric mucosa, TGF-α, Cripto, and AR immunoreactivities were observed in thesurface epithelial and parietal cells of gastric fundicglands, respectively. EGF immunoreactivity was notobserved in any of normal mucosa examined. EGFR immunoreactivity was detected on foveolar cellsin proliferative zones and in parietal cells. Doubleimmunostaining revealed that EGFR immunoreactivity wasdistributed much more widely than PCNA immunoreactivity. PCNA positive epithelial cells adjacent togastric ulcer margin expressed relatively intense EGFRbut did not express any of the growth factors examined.On the other hand, relatively intense immunoreactivity of both TGF-α and Cripto was detected inPCNA-negative regenerative epithelium located distantfrom gastric ulcer margin. Relative immunoreactivity ofAR in regenerative gastric epithelium associated with ulcer was not different from that innormal gastric mucosa. TGF-α, AR, and Cripto areconsidered to play important roles in normal gastricmucosal proliferation, and TGF-α and Cripto may be involved in ulcer healing, possibly via aparacrine mechanism.
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