Cyclin-D1-gene amplification and expression in breast carcinoma: relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression

Int J Cancer. 1997 Apr 22;74(2):171-4. doi: 10.1002/(sici)1097-0215(19970422)74:2<171::aid-ijc5>;2-w.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Southern
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • Cyclins / metabolism*
  • DNA, Neoplasm / analysis
  • Female
  • Gene Amplification*
  • Humans
  • Immunohistochemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism*
  • Retinoblastoma Protein / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Oncogene Proteins
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Cyclin D1