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Stroma Adjacent to Metastatic Mature Teratoma after Chemotherapy for Testicular Germ Cell Tumors Is Derived from the Same Progenitor Cells as the Teratoma

Departments of Urology [D. W. B., R. S. F., L. C.], Pathology and Laboratory Medicine [T. M. U., O. W. C., S. Z., J. N. E., L. C.], and Internal Medicine [C. J. S.], Indiana University School of Medicine, Indianapolis, Indiana 46202

Metastatic mature teratoma is often present in postchemotherapy surgical specimens of lymph nodes from patients with pathological stage II or III testicular germ cell tumors. The stromal cells in these lesions have generally been considered "fibrosis" secondary to the chemotherapy and the necrosis it causes, although the frequent cytological atypia of the stromal cells suggests that they may be neoplastic. We studied 25 patients with pathological stage II or III testicular cancer who were treated with platinum-based chemotherapy followed by surgical resection of retroperitoneal lymph nodes that contained metastatic mature teratoma with "fibrosis" to determine the reactive or neoplastic nature of the stromal cells. We compared the pattern of allelic loss using nine microsatellite DNA markers (D9S177, D9S303, D9S778, D9S171, D12S1015, D1S508, D2S156, D18S46, and D11S903) between the epithelial cells of the teratoma and the cells in the adjacent stroma. A laser capture microdissection technique facilitated preparation of genomic DNA from the epithelial components of teratoma, adjacent stromal cells, and normal lymph node tissue from each patient. Of the 25 patients, loss of heterozygosity was seen at a minimum of one focus in 22 (92%) of the teratoma specimens and 16 (64%) of the adjacent stroma. Of the 16 cases for which the stroma showed loss of heterozygosity, 8 cases showed the identical pattern of allelic loss in the epithelial cells of the adjacent teratoma at all nine DNA loci studied. The remaining eight cases showed similar allelic loss in at least one of the nine DNA loci analyzed. Interestingly, three cases showed loss of heterozygosity in the stroma that was not seen in the matching teratoma specimens. Our results indicate that the stromal cells adjacent to metastatic mature teratoma in postchemotherapy lymph node specimens frequently have genetic abnormalities similar to the metastatic teratoma. Concordant genetic alterations observed in teratoma and stroma suggest that both are derived from the same element of the original germ cell tumor or the same progenitor cell.

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