title: Do poor-prognosis breast tumours express membrane cofactor proteins (CD46)?
abstract: CD46 or membrane cofactor protein (MCP) is a complement regulatory protein that has been identified on all nucleated cells and which protects them from attack by autologous complement. Breast carcinomas are reported to consistently express CD46.
  
  
  OBJECTIVE
  Our previous immunohistochemical study showed that in breast carcinomas, loss of CD59 and CD55 correlated with poor survival. This study aimed to investigate the prognostic significance of CD46 on breast tumours using a rabbit polyclonal anti-CD46 antibody with a standard immunohistochemistry method. A total of 510 breast tissues from patients with primary operable breast cancer diagnosed between 1987 and 1992 had previously been included in tissue microarrays. They included patients 70 years of age or less (mean = 54 years) with a long-term follow-up (median = 82 months).
  
  
  RESULTS
  Immunohistochemical study revealed that 507/510 (99.4%) of breast tumours expressed CD46. Strong immunoreactivity was exhibited by 136/510 (27%) tumours, while moderate and weak staining was observed in 43% and 29% of tumours, respectively. Intensity of CD46 expression was significantly associated with tumour grade (p < 0.05), histological type of tumour (p < 0.001) and tumour recurrence (p < 0.05). There was no correlation with lymph node stage or the presence of vascular invasion, nor with patient age or menopausal status. Interestingly, as most tumours expressed CD46, it would appear that poor-prognosis tumours that lose CD55 and CD59 still express CD46.
  
  
  CONCLUSIONS
  Breast tumours express high levels of CD46 that correlates with tumour grade and recurrence. It is therefore likely that loss of CD55 and CD59 could be compensated by expression of CD46. However, loss of CD55 and CD59, even for tumours that still express CD46, is still associated with a poor prognosis. This may suggest that CD46 alone can protect from complement lysis but that loss of CD55 and CD59 are associated with other roles in immune regulation.
authors.affiliation: CRC Academic Department of Clinical Oncology, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Madjd
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: John
authors.initials: J
authors.lastname: Ronan
authors.forename: Sarah
authors.initials: S
authors.lastname: Lewis
authors.forename: Neil K
authors.initials: NK
authors.lastname: Rushmere
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D003169:Complement Inactivator Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins