Instability of xenotransplanted soft tissue sarcomas. Morphologic and flow cytometric results

Human tumors transplanted into nude mice are widely considered to be identical to the tumor of origin. In addition, high histologic constancy of xenografts over many passages is generally accepted. We have checked these prerequisites for a therapy-orientated application of the nude mouse model using soft tissue sarcomas. Twenty-two primary soft tissue sarcomas and their xenografts were compared histologically and flow cytometrically over numerous passages. More than 30% of transplants showed a variation in cell differentiation, cell content, frequency of mitosis, tendency to necrotize, and connective tissue content compared to the original tumor. Furthermore, transplants from various regions in one tumor showed divergent results. Analyses of serial transplants showed histologic and flow cytometrical discrepancies in about 50% of cases, and new cell lines occurred in 26%. Our results show that the genetic instability found in human neoplasias also applies to xenotransplants and that the therapy-related usefulness of the nude mouse model is limited.