Bechmann Marc B, Brydholm Andreas V, Codony Victoria L, Kim Jiyoung, Villadsen René
Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Stem Cell Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Oncotarget. 2020 Oct 27;11(43):3886-3899. doi: 10.18632/oncotarget.27778.
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.
癌胚抗原相关细胞黏附分子5（CEACAM5）在许多原发性乳腺癌中过表达。然而，CEACAM5在乳腺癌发生中的具体作用仍未明确。在此，我们通过免疫组织化学检查了一个包含110例冷冻保存的原发性乳腺癌的样本库，以评估CEACAM5在肿瘤亚型中的分布。大多数雌激素受体阳性和HER2过表达的肿瘤为CEACAM5阳性，而大多数三阴性肿瘤为阴性。对总共59例患者的配对原发性乳腺癌和相应淋巴结病变样本集进行评估发现，原发性肿瘤和淋巴结在CEACAM5状态方面具有高度相关性。然而，有相当一部分样本集在原发性肿瘤、转移灶或两者中都表现出肿瘤内异质性，这表明CEACAM5阳性和阴性细胞都可能在肿瘤播散中发挥作用。在培养试验中检测CEACAM5在乳腺癌细胞系中的表达结果时，我们发现表达CEACAM5的细胞侵袭性较低。在生存分析中，通过乳腺癌队列研究发现，CEACAM5的表达根据分子亚型预测不同的临床结果。总之，我们的分析表明CEACAM5在乳腺癌中发挥着依赖于背景的作用，值得进一步研究。
