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Cell cycle marker expression in benign and malignant intraductal papillary lesions of the breast
  1. Seow Foong Loh1,
  2. Caroline Cooper2,3,
  3. Christina I Selinger2,
  4. Elizabeth H Barnes4,
  5. Charles Chan3,5,
  6. Hugh Carmalt1,3,
  7. Richard West1,3,
  8. Laurence Gluch3,6,
  9. Jane M Beith3,7,
  10. C Elizabeth Caldon8,9,
  11. Sandra O'Toole2,3,8,9
  1. 1Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  2. 2Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  3. 3Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  4. 4NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
  5. 5Anatomical Pathology Department, Concord Repatriation General Hospital, Concord, New South Wales, Australia
  6. 6Department of Breast and Endocrine Surgery, Concord Hospital, Sydney, New South Wales, Australia
  7. 7Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia
  8. 8The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
  9. 9Faculty of Medicine, St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
  1. Correspondence to Professor Sandra O'Toole, Department of Tissue Pathology and Diagnostic Oncology, Building 94, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia; Sandra.o'toole@sswahs.nsw.gov.au

Abstract

Aims 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.

  • CANCER
  • CELL CYCLE REGULATION
  • HISTOPATHOLOGY
  • TUMOUR MARKERS
  • BREAST PATHOLOGY

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