Immunohistochemical detection of cripto-1, amphiregulin and transforming growth-factor-alpha in human gastric carcinomas and intestinal metaplasias.

The expression and localization of cripto-1 (CR-1), amphiregulin (AR) and transforming growth factor alpha (TGFalpha) were assessed by immunocytochemistry in 37 primary human gastric tumors, 30 noninvolved gastric mucosa samples that were adjacent to carcinoma but exhibited intestinal metaplasia and 37 adjacent, noninvolved gastric mucosa samples. Seventeen (46%), nineteen (51%) and twenty-one (57%) carcinomas showed staining for CR-1, AR and TGFalpha, respectively; whereas sixteen (53%), eight (26%) and five (17%) intestinal metaplasias were reactive with the anti-CR-1, anti-AR and anti-TGFalpha antibodies, respectively. In contrast, none of the normal, noninvolved gastric mucosa samples reacted with the TGFalpha antibody and only 1 (3%) of these samples showed weak staining with the anti-CR-1 antibody. However, 8 (21%) of the normal gastric mucosa samples showed moderate levels of staining with the AR antibody. Within the carcinomas, there was a slight trend for association between TGFalpha and CR-1 expression (p<0.05), but no correlation was found between epidermal growth factor receptor and CR-1 expression. Staining for p53 was observed in 26 (70%) of the carcinomas, 3 (10%) intestinal metaplasias and none of the gastric mucosa samples. This data demonstrate that CR-1, like TGFalpha, may be a tumor marker for a subset of gastric carcinomas in addition to being an important factor in the early stages of gastric cancer development.