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01-06-2010 | Preclinical study

Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma

Authors: Mohamed Kamal, Abeer M. Shaaban, Liqun Zhang, Clare Walker, Sally Gray, Nalin Thakker, Carmel Toomes, Valerie Speirs, Sandra M. Bell

Published in: Breast Cancer Research and Treatment | Issue 3/2010

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.

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Title: Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma
Authors: Mohamed Kamal
Abeer M. Shaaban
Liqun Zhang
Clare Walker
Sally Gray
Nalin Thakker
Carmel Toomes
Valerie Speirs
Sandra M. Bell
Publication date: 01-06-2010
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0500-4

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