title: Microcephalin is a new novel prognostic indicator in breast cancer associated with BRCA1 inactivation.
abstract: The authors have investigated the expression of the microcephalin (MCPH1) protein to evaluate its prognostic importance in breast cancer. Microcephalin is a damage response protein involved in the regulation of BRCA1 and BRCA2. BRCA1 mutations are often associated with basal-like breast cancer, which are also often negative for oestrogen receptor (ER), progesterone receptor (PR) and HER2. MCPH1 immunohistochemistry was performed on 319 breast cancers prepared as tissue microarray and correlated with pathology, survival, ER, PR, HER2, EGFR, CK5/6, CK14 and BRCA1 expression. After performing continuous data analysis, mean microcephalin expression decreased with increasing grade (P < 0.006). Mean microcephalin expression was lower in ER/PR negative (P < 0.001) and triple negative cancers (P < 0.004). Conversely, an association with HER2-positive cancers was also identified (P < 0.034). Reduced microcephalin also correlated with reduced nuclear BRCA1 staining (P < 0.001). No association was identified with basal markers. After dichotomising the data into low and high microcephalin expression, reduced expression was identified in 29% (93/319) of breast cancers. An association with low expression was identified in invasive ductal carcinomas with breast cancer-specific survival (BCSS) (P = 0.052). Multivariate analysis of ductal carcinomas showed that microcephalin, together with lymph node involvement and tumour size were independent predictors of BCSS (P = 0.037). Microcephalin expression is reduced in 29% of breast cancers, particularly in higher grade tumours and BRCA1-negative cases. Microcephalin is an independent predictor of BCSS in invasive ductal breast cancer patients and may prove to be a useful biomarker for the identification of aggressive breast cancers.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Richardson
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Shaaban
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kamal
authors.forename: Rawiah
authors.initials: R
authors.lastname: Alisary
authors.forename: Clare
authors.initials: C
authors.lastname: Walker
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Valerie
authors.initials: V
authors.lastname: Speirs
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Bell
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D046888:Tissue Array Analysis
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C460645:MCPH1 protein, human; C508053:ERBB2 protein, human