title: Determination of the prognostic value of cyclin D1 overexpression in breast cancer.
abstract: 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.
authors.affiliation: Department of Pathology, Royal Victoria Infirmary, University of Newcastle upon Tyne, UK.
authors.forename: G G
authors.initials: GG
authors.lastname: McIntosh
authors.forename: J J
authors.initials: JJ
authors.lastname: Anderson
authors.forename: I
authors.initials: I
authors.lastname: Milton
authors.forename: M
authors.initials: M
authors.lastname: Steward
authors.forename: A H
authors.initials: AH
authors.lastname: Parr
authors.forename: M D
authors.initials: MD
authors.lastname: Thomas
authors.forename: J A
authors.initials: JA
authors.lastname: Henry
authors.forename: B
authors.initials: B
authors.lastname: Angus
authors.forename: T W
authors.initials: TW
authors.lastname: Lennard
authors.forename: C H
authors.initials: CH
authors.lastname: Horne
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D016213:Cyclins; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D066246:ErbB Receptors