Diploicin

Biological characteristics of a tumor are primarily affected by its genomic alterations. It is thus important to ascertain whether there are genomic changes linked with DNA ploidy and/or chromosomal instability (CIN). In the present study, using fresh-frozen samples of 46 invasive breast cancers, laser scanning cytometry, array-based comparative genomic hybridization, and chromosome fluorescence in situ hybridization were performed to assess DNA ploidy, DNA copy number aberrations (DCNAs), and CIN status. Both ploidy and CIN status were examined in 36 tumors, resulting in 23 aneuploid/CIN+ tumors, 1 aneuploid/CIN-, 2 diploid/CIN+, and 10 diploid/CIN- tumors. Comparison of the aCGH data with the DNA ploidy and CIN status identified cytogenetically 11 characteristic breast cancers with distinctive DCNAs. The 11 tumors were classified into two types; one type is diploid/CIN- phenotype containing 4 DCNAs, and the other aneuploid/CIN+ phenotype containing 7 DCNAs. In 30 (65.2%) of the 36 breast cancers, the status of DNA ploidy and CIN depended on the type of DCNAs. Furthermore, the DNA ploidy phenotype depended on the dominant type of DCNAs even in tumors with a mixture of multiple DCNAs of one type and a single DCNA of the other type. Tumors with multiple DCNAs of both types represented aneuploidy and over three quarters of breast cancers carry at least one type of the DCNAs. These results suggested that, in breast cancers, the status of DNA ploidy and CIN was likely to determine at the beginning of carcinogenesis.

Background: The St Gallen International Expert Consensus 2011 has proposed a new classification system for breast cancer. The purpose of this study was to elucidate the relationship between the breast cancer subtypes determined by the new classification system and genomic characteristics. Methods: Invasive breast cancers (n = 363) were immunohistochemically classified as follows: 111 (30.6%) as luminal A, 95 (26.2%) as luminal B (HER2 negative), 69 (19.0%) as luminal B (HER2 positive), 41 (11.3%) as HER2, and 47 (12.9%) as basal-like subtypes. Results: The high expression of Ki-67 antigen was detected in 236 tumors; no cases of luminal A subtype showed high expression of the Ki-67 antigen, but more than 85% of tumors of the other subtypes showed high expression. In addition, DNA ploidy and chromosomal instability (CIN) were assessed using imaging cytometry and FISH, respectively. In this series, 336 (92.6%) tumors consisted of 129 diploid/CIN- and 207 aneuploid/CIN + tumors. Diploid/CIN- and aneuploid/CIN+ features were detected in 64.9% and 27.9% of luminal A, 41.1% and 49.5% of luminal B (HER2-), 11.6% and 81.2% of luminal B (HER2+), 4.9% and 90.2% of HER2, and 17.0% and 76.6% of basal-like subtypes, respectively. Unlike the luminal B (HER2+), HER2 and basal-like subtypes, the luminal A and luminal B (HER2-) subtypes were heterogeneous in terms of DNA ploidy and CIN. Conclusions: It is reasonable to propose that the luminal A and luminal B (HER2-) subtypes should be further divided into two subgroups, diploid/CIN- and aneuploid/CIN+, based on their underlying genomic status.