Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer

Summary Cell division cycle 7 is a widely expressed protein kinase implicated in cell division, cell cycle checkpoint mechanisms, and cancer progression. To determine the relationship of cell division cycle 7 protein expression with tumor phenotype, molecular features and prognosis, 2197 highly characterized breast carcinomas were analyzed on a tissue microarray. Detectable cell division cycle 7 expression was found in 1088 (57%) of breast cancer specimens and 228 (11.9%) exhibited a moderate or strong expression. High levels of cell division cycle 7 expression were significantly related to medullary histotype ( P < .0001); high tumor grade ( P < .0001); negative estrogen receptor status ( P < .0001); high Ki67 expression level ( P < .0001); p53 and p16 overexpression ( P < .0001); and amplification of HER2 ( P < .0001), c- myc ( P < .0001), MDM2 ( P = .043), CCND1 ( P = .0084), and ESR1 ( P = .0012) as well as with the number of amplified genes ( P < .0001). There was also a tendency towards worse prognosis in cell division cycle 7 positive as compared to negative breast cancers. The relationship between cell division cycle 7 and number of amplifications was independent from tumor proliferation raising the possibility of a direct influence of cell division cycle 7 expression for amplification development. In conclusion, cell division cycle 7 is a replication associated protein with relationships to gene amplification and genomic instability in breast carcinomas. These data support the potential utility of newly developed small molecule cell division cycle 7 inhibitors as a therapeutic alternative in at least a subset of breast carcinomas.