Seow Foong Loh1, Caroline Cooper2, Christina I Selinger3, Elizabeth H Barnes4, Charles Chan5, Hugh Carmalt6, Richard West6, Laurence Gluch7, Jane M Beith8, C Elizabeth Caldon9, Sandra O'Toole10. 1. Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 2. 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. 3. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 4. NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia. 5. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia Anatomical Pathology Department, Concord Repatriation General Hospital, Concord, New South Wales, Australia. 6. Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 7. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia Department of Breast and Endocrine Surgery, Concord Hospital, Sydney, New South Wales, Australia. 8. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 9. 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. 10. 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.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Entities:
Keywords:
BREAST PATHOLOGY; CANCER; CELL CYCLE REGULATION; HISTOPATHOLOGY; TUMOUR MARKERS
Authors: Young Ran Hong; Byung Joo Song; Sang Seol Jung; Bong Joo Kang; Sung Hun Kim; Byung Joo Chae Journal: J Breast Cancer Date: 2016-12-23 Impact factor: 3.588
Authors: Na Chang; Lei Tian; Xiaofang Ji; Xuan Zhou; Lei Hou; Xinhao Zhao; Yuanru Yang; Lin Yang; Liying Li Journal: Cells Date: 2019-09-11 Impact factor: 6.600