HUMAN VILLOUS ADENOMAS ENGRAFTED INTO ACID MICE SURVIVE FOR PROLONGEDPERIOD WITHOUT MALIGNANT TRANSFORMATION

Human villous adenomas are thought to represent premalignancies that s ubsequently give rise to colorectal adenocarcinomas. Currently there i s no in vivo model in which to study the dedifferentiation and maligna nt transformation of these tumors. We establish here that human villou s adenomas can be successfully engrafted into severe combined immunode ficient (scid) mice. Furthermore, these xenografts remain viable for u p to 18 mo after either a subcutaneous or intraperitoneal inoculation of the human tissue. Tumors grew slowly and secreted a clear mucinous fluid. Examination of the tumors histologically at 1, 4, and 12 mo aft er implantation revealed that the villous polypoid structure was maint ained and islands of atypical cells were observed within pockets of mu cin surrounding the adenomatous tissue. No gross or histologic evidenc e of malignancy was detected throughout the 20-mo observation period. The human identity of the cells in the graft was confirmed by DNA in s itu hybridization with a human-specific probe. We conclude that the hu man-scid xenograft described here represents a viable animal model wit h which to study the potential malignant dedifferentiation of villous adenomas over a prolonged period of time and to evaluate the possible contribution of selected oncogenic vectors on the malignant transforma tion of these adenomas.