Unusual clonal chromosomal evolution in a breast carcinoma and its lymph node metastasis in a patient with Down syndrome.

A cytogenetic study was performed on a primary breast carcinoma and its axillary lymph node metastasis from a 53-year-old patient with trisomy 21, a carrier of a constitutional der(21;21). A translocation t(X;21) and the loss of the other X chromosome were shared by all karyotypes from tumor cells. The primary tumor was hyperdiploid with several gains of whole chromosomes. In contrast, most cells from the metastasis shared several rearrangements and losses leading to a hypodiploid karyotype. No normal chromosome 17 was present; instead, an i(17)(q10) and a fragment, detected by chromosome painting and presumably corresponding to a rearranged 17p, were found. Immunostaining for p53 was strongly positive in the metastasis but not in the primary tumor, suggesting a mutation of the TP53 gene in the metastasis. Finally, a small cell population of the metastasis was hyperdiploid like the clone in the primary tumor, suggesting that the node was colonized twice, at an early stage and a later stage of the clonal evolution of the tumor.