In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 46-46
Abstract:
Purpose: Breast cancer brain metastases (BCBM) are detected with increasing incidence. Therefore, identification of genes involved in BCBM formation is of great interest. Eperimental Design: In order to detect potential genes involved in BCBM, we first screened for genes down-regulated by methylation in cell lines with site-specific metastatic ability. The expression of five genes, CADM1, SPARC, RECK, TNFAIP3 and CXCL14, which were also found down-regulated in gene expression profiling analyses of BCBM tissue samples, were verified by qRT-PCR in a larger patient cohort. CADM1 was chosen for further down-stream analyses. Results: A higher incidence of CADM1 methylation, correlating with the expression levels, was found in BCBM as compared to non-matched primary BC. Similarly, loss of CADM1 protein expression was detected more commonly among BCBM samples as well as among primary breast tumors with subsequent brain relapse. The prognostic role of CADM1 expression was finally verified in two publicly available data sets (n=418) and in two large independent primary breast cancer TMA tumor cohorts (n=1718). The immunohistochemical analyses revealed an association between loss of CADM1 protein expression and risk factors such as disease stage, lymph node status, and tumor size in primary BC. Furthermore, all analyses revealed a significant association between CADM1 and shorter survival. In multivariate analyses, survival was significantly longer for patients with CADM1-positive primary tumors for both TMA data sets (p= 0.04 and p=0.01). Conclusions: Loss of CADM1 expression is an independent prognostic factor especially associated with the development of brain metastases in breast cancer patients. Citation Format: Harriet Wikman, Laura Westphal, Felicitas Schmid, Markus Glatzel, Jakob Matschke, Manfred Westphal, Sirkku Pollari, Kristiina Iljin, Luigi Terracciani, Heini Huhtala, Anne Kallioniemi, Guido Sauter, Volkmar Müller, Isabell Witzel, Katrin Lamszus, Dirk Kemming, Klaus Pantel. Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 46. doi:10.1158/1538-7445.AM2014-46
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-46
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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