title: Cell cycle marker expression in benign and malignant intraductal papillary lesions of the breast.
abstract: OBJECTIVE
  The diagnosis of intraductal papillary lesions of the breast on core biopsy remains challenging in pathology, with most patients requiring formal surgical excision for a definitive diagnosis. The aim of this study was to determine whether a representative panel of proliferative cell cycle immunohistochemical markers (cyclin A2, cyclin B1 and cyclin D1) could improve the specificity of pathological diagnosis of these lesions.
  
  
  METHODS
  A series of 68 surgically excised intraductal papillary lesion cases were retrospectively selected, and immunohistochemistry for cyclin A2, cyclin B1 and cyclin D1 was performed.
  
  
  RESULTS
  Cyclin B1 (OR 1.80, 95% CI 1.01 to 3.2, p=0.046) and cyclin D1 (OR 1.13, 95% CI 1.05 to 1.22, p=0.002) expression was independently associated with a diagnosis of malignancy in papillary lesions, although expression was frequently heterogeneous and only focal. Cyclin A2 expression (OR 0.76, 95% CI 0.41 to 1.4, p=0.38) was not associated with a malignant diagnosis in multivariable logistic regression models. All three cyclins displayed high sensitivity (80%-95%) for a diagnosis of malignancy, although cyclin B1 showed a superior specificity of 72.7% compared with the low specificity of cyclins A2 and D1.
  
  
  CONCLUSIONS
  Our study has identified for the first time that the expression of key cell cycle markers differs between benign and malignant papillary breast lesions and identified changes to the mitotic marker, cyclin B1, as particularly significant. However, given the low level and heterogeneous nature of expression of these markers, there remains a significant risk of undersampling in core biopsies and thus they are unlikely to be useful in routine clinical practice.
authors.affiliation: Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: Seow Foong
authors.initials: SF
authors.lastname: Loh
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Selinger
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Barnes
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia Anatomical Pathology Department, Concord Repatriation General Hospital, Concord, New South Wales, Australia.
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Hugh
authors.initials: H
authors.lastname: Carmalt
authors.affiliation: Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: West
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia Department of Breast and Endocrine Surgery, Concord Hospital, Sydney, New South Wales, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gluch
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Beith
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia Faculty of Medicine, St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: C Elizabeth
authors.initials: CE
authors.lastname: Caldon
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia Faculty of Medicine, St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: O'Toole
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D056751:Cyclin A2 / Q000032:analysis*; D056744:Cyclin B1 / Q000032:analysis*; D019938:Cyclin D1 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D018300:Papilloma, Intraductal / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C503721:CCNA2 protein, human; C534699:CCNB1 protein, human; C530104:CCND1 protein, human; D056751:Cyclin A2; D056744:Cyclin B1; D019938:Cyclin D1
keywords: BREAST PATHOLOGY; CANCER; CELL CYCLE REGULATION; HISTOPATHOLOGY; TUMOUR MARKERS