High Notch1 protein expression is an early event in breast cancer development and is associated with the HER‐2 molecular subtype |
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| Authors: | Sarah J Zardawi Ibrahim Zardawi Catriona M McNeil Ewan K A Millar Duncan McLeod Adrienne L Morey Paul Crea Niamh C Murphy Mark Pinese Elena Lopez‐Knowles Samantha R Oakes Christopher J Ormandy Min Ru Qiu Anne Hamilton Andrew Spillane Cheok Soon Lee Robert L Sutherland Elizabeth A Musgrove Sandra A O’Toole |
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| Institution: | 1. Cancer Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital, Darlinghurst;2. Department of Anatomical Pathology, HAPS, John Hunter Hospital, New Lambton;3. Department of Medical Oncology, University of Sydney, Westmead Hospital, Westmead;4. Department of Anatomical Pathology, South Eastern Area Laboratory Service, St George Hospital, Kogarah;5. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown;6. Department of Anatomical Pathology, Sydpath;7. Department of Surgery, St Vincent’s Hosptial, Darlinghurst;8. Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown and University of Sydney;9. Mater Hospital, North Sydney;10. Bosch Institute, University of Sydney and School of Medicine, University of Western Sydney;11. Faculty of Medicine, St Vincent’s Clinical School, University of NSW, Sydney, NSW, Australia |
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| Abstract: | Zardawi S J, Zardawi I, McNeil C M, Millar E K A, McLeod D, Morey A L, Crea P, Murphy N C, Pinese M, Lopez‐Knowles E, Oakes S R, Ormandy C J, Qiu M R, Hamilton A, Spillane A, Soon Lee C, Sutherland R L, Musgrove E A & O’Toole S A(2010) Histopathology 56, 286–296 High Notch1 protein expression is an early event in breast cancer development and is associated with the HER‐2 molecular subtype Aims: Activation of Notch signalling results in hyperplasia and tumorigenesis in murine mammary epithelium. However, there is little information regarding the expression of Notch1 in premalignant lesions and early breast cancer. We investigated expression of Notch1 in breast cancer development and its association with molecular subtypes. Methods and results: Immunohistochemical expression of Notch1 was determined in a murine model of mammary carcinogenesis and in breast tissue from two cohorts of breast cancer patients, the first (n = 222) comprising a histological progression series and the second an outcome series of 228 patients with operable invasive ductal carcinoma. Enhanced expression of Notch1 protein was an early event in both murine and human breast cancer development with progressive increases in expression with the development of hyperplasia and malignancy. High Notch1 was not prognostic in the outcome cohort. There was, however, a highly significant association of high Notch1 protein with the HER‐2 molecular subtype of breast cancer (P = 0.008). Conclusions: These data demonstrate that aberrant Notch regulation is an early event in mammary carcinogenesis and is associated with the HER‐2 molecular subtype of breast cancer, and suggest the Notch signalling pathway may be a potential therapeutic target worthy of further investigation. |
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| Keywords: | breast cancer developmental signalling pathways Notch1 |
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