Immunohistochemical localization of FAP-1, an inhibitor of Fas-mediated apoptosis, in normal and neoplastic human tissues

Fas, a death receptor, is widely expressed in human tissue, but its express ion, although a prerequisite for the induction of apoptosis, does not predi ct its biological function. To understand the mechanisms of Fas resistance in human tissues in vivo, we performed immunohistochemistry using an antibo dy against Fas-associated phosphatase-1 (FAP-1), which interacts with the c ytosolic domain of Fas and inhibits Fas-mediated apoptosis. In normal human tissues, FAP-1 immunostaining was easily detected, for example, in renal t ubules, skeletal muscle, myocardiocytes, pituitary gland, parathyroid gland , pancreatic islets, hepatocytes, testicular germ cells, prostatic glands, neurons, epithelium of fallopian tube, endometrial glands, trophoblasts, br onchial epithelial cells, and some types of gastrointestinal epithelial cel ls. In 123 (78%) of 158 cancers of various origins, including breast carcin omas, stomach carcinomas, colon carcinomas, lung carcinomas and several typ es of sarcomas, variable intensities of FAP-1 expression were evident. Take n together, these findings demonstrated that FAP-1 is widely expressed in n ormal human tissues and partly overlapped with Fas expression described in earlier reports, suggesting that FAP-1 may have an important role in the re gulation of apoptosis in vivo. In addition, FAP-1 expression in cancers sug gests that many cancers may be resistant to Fas-mediated apoptosis through the action of FAP-1 in vivo.