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
ofCSMD1 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. |
