Abstract
CEACAM5 is overexpressed in many primary breast carcinomas. However, the exact role of CEACAM5 in breast cancer tumorigenesis remains unresolved. Here, we examined a repository of 110 cryopreserved primary breast carcinomas by immunohistochemistry to assess the distribution of CEACAM5 in tumor subtypes. The majority of estrogen receptor-positive and HER2-overexpressing tumors were CEACAM5-positive, whereas most of Triple-negative tumors were negative. Assessing sample sets of paired primary breast cancers and corresponding lymph node lesions from a total of 59 patients revealed a high correlation between primary tumor and lymph node with regard to CEACAM5-status. However, a notable subset of sample sets demonstrated intratumoral heterogeneity in the primary tumor, the metastatic lesion or both, suggesting that both CEACAM5-positive and –negative cells can play a role in tumor dissemination. When examining the consequence of expression of CEACAM5 in breast cancer cell lines in culture assays we found that CEACAM5-expressing cells were less invasive. In survival analysis, using cohort studies of breast cancer, expression of CEACAM5 predicted different clinical outcomes depending on molecular subtypes. Altogether, our analysis suggests that CEACAM5 plays a context-dependent role in breast cancer that warrants further investigation.
Highlights
The carcinoembryonic antigen family (CEA) consists of a subgroup of 12 members of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), and several of these are reportedly overexpressed in various cancers [1, 2]
In a search for CEACAM5-specific antibodies that work optimally for immunohistochemistry on cryosectioned breast cancer tissue, we tested three monoclonal antibodies: CB30, COL-1 and 1105, all of which have been utilized in previous studies by other groups [28,29,30]
We found that the staining pattern of monoclonal antibodies (mAbs) 1105 was correlated with expression of another CEA family member, CEACAM6 (Figure 1A)
Summary
The carcinoembryonic antigen family (CEA) consists of a subgroup of 12 members of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), and several of these are reportedly overexpressed in various cancers [1, 2]. Work suggested that CEACAM5 was often overexpressed in breast cancer [4]. While some studies have demonstrated that increased serum levels in preoperative breast cancer patients do correlate to a worse outcome [5,6,7,8] others have not [9,10,11]. To add to the complexity some noted a statistical significance only for subsets of the patient samples that was analyzed [22, 23] and one study even found an inverse correlation between CEACAM5-positivity and outcome [24]. Reports on the proportion of CEACAM5-positive breast cancers vary greatly, from a few to more than 80%, which at least in part may explain the discrepancies with regard to the clinical value of this marker [4, 13, 17, 21, 23, 25–
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