High levels of DNA index heterogeneity in advanced breast carcinomas. Evidence for DNA ploidy differences between lymphatic and hematogenous metastases

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Abstract
Background. The aim of this study was to investigate DNA ploidy status and DNA index heterogeneity of lymphatic and hematogenous metastases of advanced breast carcinomas and the relations among the various tumor sites. Methods. DNA ploidy status was analyzed by flow cytometry on frozen and paraffin-embedded tissue blocks taken from primary and metastatic tumor sites in 18 patients with advanced breast cancer. Results. Presumably because of the extensive sampling, high percentages of DNA aneuploidy, DNA multiploidy, and DNA index heterogeneity were found in primary breast carcinomas as well as in lymph node and distant metastases. DNA aneuploid tumor stemlines were frequently accompanied by DNA diploid tumor stemlines. Most of the DNA tumor stemlines found in the primary tumors recurred in lymph node (55%) and distant (59%) metastases, even after 17 years of relapse-free survival. DNA tumor stemlines found in distant metastases, however, often differed from those in lymph node metastases (61%). Conclusions. A marked DNA index heterogeneity can be found in primary and metastatic tumor sites when appropriate sampling is applied. There were no DNA ploidy subclasses, notably absent in either type of metastasis, indicating similar metastatic capacities of both DNA aneuploid and DNA diploid tumor stemlines in advanced breast carcinomas. The difference in DNA ploidy status between lymphatic and hematogenous metastases suggest that these metastases can be generated independently.