Biomaterial-induced sarcoma - A novel model to study preneoplastic change

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers, The recognition of the adenom acarcinoma sequence both in humans and in animal experimental models has gi ven the field of basic ontology the opportunity to elucidate individual mec hanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampere d understanding of the molecular genetic steps involved, We present an expe rimental model in the rat in which a high incidence of malignant mesenchyma l tumors arise around a subcutaneously implanted biomaterial. Nine commerci ally available biomaterials were implanted in a total of 490 rats of the Fi scher strain for 2 years, On average, macroscopic tumors were found in 25.8 % of implantation sites over a period from 26 to 110 weeks after implantati on, The most frequent tumors mere malignant fibrous histiocytomas and pleom orphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic prolifera tion to incipient sarcoma could be observed, A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear anti gen was of particular help in identifying these atypical proliferative lesi ons. To our knowledge this is the first description of a sarcoma model in w hich preneoplastic lesions can be readily identified and also reproducibly induced, This model provides the molecular biologist with defined stages in the development of mesenchymal ma lignancy, with which the multistage tumo rigenesis hypothesis can be tested, analogous to the well-known adenoma-car cinoma sequence.