Cyclin-D1-gene amplification and expression in breast carcinoma: relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression.
Cyclin D1 is a major positive regulator of the G1 restriction point promoting inactivation of the retinoblastoma protein (RB). The cyclin D1 gene is rearranged, amplified and/or over-expressed in several human neoplasms. In the present series of 64 human breast carcinomas, cyclin D1 amplification (4- to 8-fold) was seen in 24% of cases, and cyclin-D1 immunohistochemical over-expression was seen in 50% of cases. Amplification and over-expression were statistically associated; however, divergent result were seen in 30% of cases. Some of these discrepancies may reflect the fact that cyclin-D1 expression may be due to mechanisms other than gene amplification. Cyclin-D1 over-expression, but not cyclin-D1 amplification, was associated with positive oestrogen-receptor immunoreactivity. Cyclin-D1 amplification was associated with high RB expression, and 4 cases (7%) with absent RB immunoreactivity showed no cyclin-D1 amplification nor expression. Our data support the hypothesis that cyclin-D1 amplification may be associated with enhanced gene transcription and with high RB expression, that high ER expression may cooperate in maintaining high levels of cyclin-D1 protein, and that loss of RB function, as assessed by the lack of RB immunoreactivity, may be related to normal cyclin-D1 gene copy number and low cyclin-D1 expression.
Barbareschi
M
M
Department of Histopathology, Santa Chiara Hospital, Trento, Italy.
Pelosio
P
P
Caffo
O
O
Buttitta
F
F
Pellegrini
S
S
Barbazza
R
R
Dalla Palma
P
P
Bevilacqua
G
G
Marchetti
A
A
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1