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

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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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Acknowledgments

This study was supported by grants from Yorkshire Cancer Research and Breast Cancer Campaign (SMB & VS), the Association for International Cancer Research (LZ & NT) and the Egyptian government (MK). CT is a Royal Society University Research Fellow.

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Authors and Affiliations

  1. Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, Level 8, St. James’s University Hospital, Leeds, LS9 7TF, UK

    Mohamed Kamal, Clare Walker, Carmel Toomes & Sandra M. Bell

  2. Department of Zoology, Faculty of Science, University of Benha, Benha, Egypt

    Mohamed Kamal

  3. St James’s Institute of Oncology, St James’s University Hospital, Leeds, LS9 7TF, UK

    Abeer M. Shaaban, Clare Walker & Sally Gray

  4. Department of Medical Genetics, University of Manchester, Manchester, M13 0JH, UK

    Liqun Zhang & Nalin Thakker

  5. Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, Level 4, St. James’s University Hospital, Leeds, LS9 7TF, UK

    Valerie Speirs

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  1. Mohamed Kamal
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Correspondence to Sandra M. Bell.

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Kamal, M., Shaaban, A.M., Zhang, L. et al. Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma. Breast Cancer Res Treat 121, 555–563 (2010). https://doi.org/10.1007/s10549-009-0500-4

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  • DOI: https://doi.org/10.1007/s10549-009-0500-4

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