Immunohistochemical detection and gene amplification of cyclin D1 in mammary infiltrating ductal carcinoma.
The deregulation of cyclin D1 (BCL-1, PRAD1, CCND1) protein, normally synthesized in the G1 phase of the cell cycle, has been implicated in the pathogenesis of some malignant neoplasms, including invasive mammary carcinomas. We used rabbit polyclonal antibody 19 to detect cyclin D1 in 55 infiltrating ductal carcinomas and compared the findings to six important clinicopathologic parameters and cyclin D1 gene amplification. Nuclear immunoreactivity of variable intensity for cyclin D1 was present in 35% of the neoplasms, whereas immunoreactivity of normal mammary epithelial nuclei was absent. No significant correlations were observed between immunoreactivity and patient age, axillary lymph node status, estrogen receptors, progesterone receptors, histologic grade, or any of its three components. There was a correlation between cyclin D1 immunostaining and tumor size (P = 0.013). Fourteen of 15 tumors 2 cm or less were negative, whereas 7 of 12 neoplasms larger than 4 cm were immunopositive. Fifteen percent of the invasive carcinomas had cyclin D1 gene amplification. Of these eight tumors, six showed cyclin D1 immunoreactivity (P = 0.017). In this study, cyclin D1 was detected immunohistochemically in approximately one-third of infiltrating ductal carcinomas; approximately one-third of these had detectable cyclin D1 gene amplification. These results further implicate cyclin D1 in breast tumorigenesis and are additional evidence for the role of cell cycle regulatory proteins in invasive mammary carcinoma.
Frierson
H F
HF
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Gaffey
M J
MJ
Zukerberg
L R
LR
Arnold
A
A
Williams
M E
ME
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000276:immunology*; D019938:Cyclin D1; D016213:Cyclins / Q000032:analysis* / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015513:Oncogene Proteins / Q000032:analysis* / Q000235:genetics*
D016213:Cyclins; D015513:Oncogene Proteins; D019938:Cyclin D1