title: Amplification of CCND1 and expression of its protein product, cyclin D1, in ductal carcinoma in situ of the breast.
abstract: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease clinically and biologically. The few available studies of its natural history implicate DCIS as a non-obligate precursor for invasive carcinoma. We have used fluorescence in situ hybridization (FISH) to detect gene amplification of the cell cycle regulator gene CCND1 in 88 examples of formalin-fixed, paraffin-embedded DCIS. Expression of its protein product cyclin D1 was detected by immunohistochemistry. CCND1 was amplified in 18% of DCIS cases. High grade DCIS was more likely to show amplification than low grade DCIS (32% versus 8%; P = 0.08). Gene amplification was associated with cyclin D1 protein expression (P = 0.001), although cyclin D1 was detected in cases that did not demonstrate gene amplification. Overall, cyclin D1 protein was detected in 50% of DCIS cases. Although only 2 of 23 (8%) cases of low grade DCIS had CCND1 amplification, over 50% (13/23) of these cases expressed cyclin D1 protein. Low grade DCIS had a higher mean percentage of nuclei expressing cyclin D1 than did intermediate or high grade DCIS (P = 0.007). Mechanisms other than gene amplification may be responsible for increased cyclin D1 protein in DCIS, especially in low grade DCIS. Identifying mechanisms that control cell cycle progression in DCIS may yield clues to its biological behavior.
authors.affiliation: Division of Pathology, City of Hope National Medical Center, Duarte, California, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Simpson
authors.forename: D E
authors.initials: DE
authors.lastname: Quan
authors.forename: F
authors.initials: F
authors.lastname: O'Malley
authors.forename: T
authors.initials: T
authors.lastname: Odom-Maryon
authors.forename: P E
authors.initials: PE
authors.lastname: Clarke
mesh_terms: D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015337:Multicenter Studies as Topic; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D016213:Cyclins; D015513:Oncogene Proteins; D019938:Cyclin D1