title: High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Zardawi
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Zardawi
authors.forename: Catriona M
authors.initials: CM
authors.lastname: McNeil
authors.forename: Ewan K A
authors.initials: EK
authors.lastname: Millar
authors.forename: Duncan
authors.initials: D
authors.lastname: McLeod
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Morey
authors.forename: Paul
authors.initials: P
authors.lastname: Crea
authors.forename: Niamh C
authors.initials: NC
authors.lastname: Murphy
authors.forename: Mark
authors.initials: M
authors.lastname: Pinese
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Knowles
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Oakes
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ormandy
authors.forename: Min Ru
authors.initials: MR
authors.lastname: Qiu
authors.forename: Anne
authors.initials: A
authors.lastname: Hamilton
authors.forename: Andrew
authors.initials: A
authors.lastname: Spillane
authors.forename: Cheok
authors.initials: C
authors.lastname: Soon Lee
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Musgrove
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D051881:Receptor, Notch1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D051881:Receptor, Notch1; C497761:NOTCH1 protein, human