Cytogenetic evolution in primary tumors, local recurrences, and pulmonary metastases of two soft tissue sarcomas

The karyotypic pattern at different stages of tumor development may provide information on tumor progression but few data are available regarding human solid tumors. Cytogenetic analysis was performed on the primary tumor and four lung metastases of a synovial sarcoma, and the primary tumor, two consecutive local recurrences, and six pulmonary metastases, obtained at two different occasions, of a malignant fibrous histiocytoma (MFH). Simultaneous existence of more than one cytogenetically aberrant clone was also assessed through analysis of more than one sample from the same surgical specimen. Clonal chromosome aberrations were detected in all samples from the synovial sarcoma, and in both local recurrences and five of the metastases from the MFH. All clones in both tumors were cytogenetically related. The primary synovial sarcoma tumor contained two clones, one of which was also found in the lung metastases, together with a third clone that had acquired additional aberrations. Four clones with a near-tetraploid chromosome number and complex aberrations were identified in the MFH. Likely evolutionary pathways could be deduced in both cases. In the patient with synovial sarcoma one of the pulmonary metastases, rather than the primary tumor, might well have been the source of another of the pulmonary metastases. In the MFH the cytogenetic findings indicated the presence of two co-existing lineages in the primary tumor, one giving rise to the local recurrences and one to the pulmonary metastases. Our findings show that cytogenetic analysis can be used to establish the chronologic relationships between different clones in primary tumors, local recurrences and distant metastases, to determine what genetic changes are of importance for the metastatic capability of tumor cells, and to help establish the origin of the metastatic lesions.