title: Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma.
abstract: CUB and SUSHI multiple domain protein 1 (CSMD1) is a candidate tumour suppressor gene that maps to chromosome 8p23, a region deleted in many tumour types including 50% of breast cancers. CSMD1 has homologies to proteins implicated in carcinogenesis. We aimed to study the expression pattern of the CSMD1 protein and evaluate its prognostic importance in invasive ductal carcinoma (IDC). An anti-CSMD1 antibody was developed and validated. The expression pattern of CSMD1 in normal breast and IDC samples was investigated by immunohistochemistry in 275 patients. Univariate and multivariate Cox regression analyses were performed. In normal breast duct epithelial cells, luminal, membranous and cytoplasmic CSMD1 staining was identified. Reduced expression of CSMD1 was detected in 79/275 (28.7%) of IDC cases. Low CSMD1 expression was significantly associated with high tumour grade (P = 0.003). CSMD1 expression was associated with overall survival (OS; HR = 0.607, 95%CI: 0.4-0.91, P = 0.018) but not with disease-free survival (DFS; HR = 0.81, 95%CI: 0.46-1.43, P = 0.48). Multivariate analysis showed that CSMD1, together with Nottingham Prognostic Index, was considered an independent predictor of OS (HR = 0.607, 95%CI: 0.4-0.91, P = 0.018) but not DFS (HR = 0.84, 95%CI: 0.46-1.5, P = 0.573). Reduction of CSMD1 expression was significantly associated with high tumour grade and decreased OS. Therefore, our results support the idea that CSMD1 is a tumour suppressor gene and suggest its possible use as a new prognostic biomarker. The membrane expression pattern of CSMD1 suggests that it may be a receptor or co-receptor involved in the process of signal transduction.
authors: Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, Level 8, St James's University Hospital, Leeds LS9 7TF, UK.
authors: Mohamed
authors: M
authors: Kamal
authors: Abeer M
authors: AM
authors: Shaaban
authors: Liqun
authors: L
authors: Zhang
authors: Clare
authors: C
authors: Walker
authors: Sally
authors: S
authors: Gray
authors: Nalin
authors: N
authors: Thakker
authors: Carmel
authors: C
authors: Toomes
authors: Valerie
authors: V
authors: Speirs
authors: Sandra M
authors: SM
authors: Bell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; C477880:CSMD1 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins