title: Upregulation of MICA on high-grade invasive operable breast carcinoma.
abstract: The MHC class I chain-related gene A (MICA) is frequently expressed on the surface of intestinal epithelium and by many epithelial tumours. MICA is a stress-induced antigen which was identified as an activator of natural killer cells via interaction with the NKG2D receptor. We have raised a rabbit polyclonal antibody against a synthetic peptide that recognises denatured MICA on both Western blots and in formalin-fixed paraffin-embedded sections. In the present study this antibody was used to undertake a definitive study of 530 breast cancer cases with mean follow up of 7 years to determine the prognostic significance of MICA expression. To detect any association between MICA expression and NK infiltration, whole sections of 50 tumours were also analysed for CD56 staining. Univariate analysis showed significant relationships between MICA expression and histological grade (P = 0.006), lymph node stage (P = 0.013), Nottingham Prognostic Index (NPI, P = 0.002), the presence of vascular invasion (P = 0.045) and tumour type (P = 0.023). Upregulation of MICA was more often found in histological grade 3, poor prognosis (NPI >5.4) tumours. Association of high MICA expression with NK cell infiltration was not demonstrated, as very few NK cells were present in whole breast sections. Our results suggest that induced expression of MICA may be an indicator of poor prognosis in breast carcinoma and is indicative of a tumour environment that has undergone stresses such as apoptosis, necrosis, or hypoxia.
authors.affiliation: Academic Department of Clinical Oncology, Institute of Infections, Immunity and Inflammation, University of Nottingham, City Hospital, Nottingham, NG5 1PB, United Kingdom. Zahra.Madjd@yahoo.com
authors.forename: Zahra
authors.initials: Z
authors.lastname: Madjd
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
authors.forename: Robert
authors.initials: R
authors.lastname: Moss
authors.forename: Shaun
authors.initials: S
authors.lastname: Bevin
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.forename: Nicholas F S
authors.initials: NF
authors.lastname: Watson
authors.forename: Ian
authors.initials: I
authors.lastname: Ellis
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D011817:Rabbits; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A