Determination of the prognostic value of cyclin D1 overexpression in breast cancer.
Cyclin D1 plays a critical role in the timing of the initiation of DNA synthesis in the normal cell cycle of mammalian cells. Deregulated expression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in breast cancer and B cell malignancies respectively. In order to determine the role this putative oncoprotein plays in breast cancer, we have applied a new monoclonal antibody, recently produced in our laboratory, in an immunohistochemical study of 93 primary breast carcinomas. We show that approximately 28% of the cases displayed enhanced expression of the cyclin D1 protein. Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression of any one member of this family may relieve cancer cells of their mitogenic stimulatory requirement. In addition, we show that those patients whose breast cancers co-express cyclin D1 with either epidermal growth factor receptor (EGFR) or the retinoblastoma protein (pRB) have a significantly poorer prognosis in comparison to those expressing cyclin D1 alone. Our observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy.
McIntosh
G G
GG
Department of Pathology, Royal Victoria Infirmary, University of Newcastle upon Tyne, UK.
Anderson
J J
JJ
Milton
I
I
Steward
M
M
Parr
A H
AH
Thomas
M D
MD
Henry
J A
JA
Angus
B
B
Lennard
T W
TW
Horne
C H
CH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality; D019938:Cyclin D1; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D015513:Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D011379:Prognosis; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016160:Retinoblastoma Protein / Q000032:analysis; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D016213:Cyclins; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D066246:ErbB Receptors