Clinicopathological Significance of CEACAM1 Gene Expression in Breast Cancer

10.4077/CJP.2011.AMM087

Jian-Li Wang；Rong Ma；Xun Qu；Wen-Jun Liu；Yan-Yan Wang；Cui-Xia Lv；Jing-Zhong Sun；Shan-Zhen Sun

CEACAM1 ； breast cancer ； ER ； PR ； prognosis

The Chinese Journal of Physiology

54卷5期（2011 / 10 / 01）

30 - 36

英文

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell adhesion molecule expressed in a variety of cell types. The role of CEACAM1 in breast cancer development and progression is largely unknown. Immunohistochemical analysis was used to examine CEACAM1 expression in breast cancer with long-term follow-up. CEACAM1 expression level in primary breast cancer was low or undetectable. In 65% of the cases, CEACAM1 expression within tumor tissue was lower than that in adjacent tissues. In 20% of the cases, CEACAM1 was negative. In 28.3% of cases, equivalent CEACAM1 expression level was detected in tumor and adjacent tissues. The expression level of CEACAM1 in tumor tissue was negatively correlated with patient mortality, while positively correlated with the expression level of ER+/PR+. CEACAM1 expression was not related with patients' age, pathological classification, lymphatic involvement and the size of tumor. The down-regulation of CEACAM1 was correlated with negative ER-/PR- and might be attributed to the malignant process of breast cancer. The prognosis of the patients with low CEACAM1 expression and high tumor pathological grade were poorer than those patients with high expression and low pathological grade, P＜0.05. Clinically, it is possible to predict the prognosis among the patients of breast cancer by measuring CEACAM1 gene expression in the tumor tissues.

1. Brummer, J.,Ebrahimnejad, A.,Flayeh, R.,Schumacher, U.,Loning, T.,Bamberger, A.M.,Wagener, C.(2001).Cis interaction of the cell adhesion molecule CEACAM1 with integrin beta (3).Am. J. Pathol,159,537-546.
2. Busch, C.,Hanssen, T.A.,Wagener, C.,Öbrink, B.(2002).Downregulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition.Hum. Pathol.,33,290-298.
3. Ergün, S.,Kilik, N.,Ziegeler, G.,Hansen, A.,Nollau, P.,Götze, J.,Wurmbach, J.H.,Horst, A.,Weil, J.,Fernando, M.,Wagener, C.(2000).CEA-related cell adhesion molecule 1: a potent angiogenic factor and a major effector of vascular endothelial growth factor.Mol. Cell.,5,311-320.
4. Gaur, S.,Shively, J.E.,Yen, Y.,Gaur, R.K.(2008).Altered splicing of CAECAM1 in breast cancer: identification of regulatory sequence that control splicing of CEACAM1 into long or short cytoplasmic domain isoforms.Mol. Cancer,7,46.
5. Harvey, J.M.,Clark, G.M.,Osborne, C.K.,Allred, D.C.(1999).Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer.J. Clin.. Oncol.,17,1474-1481.
6. Houde, C.,Roy, S.,Leung, N.,Nicholson, D.W.,Beauchemin, N.(2003).The cell adhesion molecule CEACAM1-L is a substrate of Caspase-3-mediated cleavage in apoptotic mouse intestinal cells.J. Biol. Chem.,278,16929-16935.
7. Kilic, N.,Oliveira-Ferrer, L.,Wurmbach, J.H.,Loges, S.,Chalajour, F.,Neshat-Vahid, S.,Weil, J.,Fernando, M.,Ergun, S.(2005).Proangiogenic signaling by the endothelial presence of CAECAM1.J. Biol. Chem.,280,2361-2369.
8. Kirshner, J.,Chen, C.J.,Liu, P.,Huang, J.,Shively, J.E.(2003).CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture.Proc. Natl. Acad. Sci. U.S.A.,100,521-526.
9. Kirshner, J.,Hardy, J.,Wilczynski, S.,Shively, J.E.(2004).Cell-cell adhesion molecule CEACAM1 is expressed in normal breast and milk and associates with betal integrin in a 3D model of morphogenesis.J. Mol. Histol.,35,287-299.
10. Kuespert, K.,Pils, S.,Hauck, C.R.(2006).CEACAMs: their role in physiology and pathophysiology.Curr. Opin. Cell. Biol.,18,565-571.
11. Laack, E.,Nikbakht, H.,Peters, A.,Kugler, C.,Jasiewicz, Y.,Edler, L.,Brümmer, J.,Schumacher, U.,Hossfeld, D.K.(2002).Expression of CEACAM1 in adenocarcinoma of the lung: a factor of independent prognostic significance.J. Clin. Oncol.,20,4279-4284.
12. Neumaier, M.,Paululat, S.,Chan, A.,Matthaes, P.,Wagener, C.(1993).Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas.Proc. Natl. Acad. Sci. USA,90,10744-10748.
13. Nittka, S.,Gunther, J.,Ebisch, C.,Erbersdobler, A.,Neumaier, M.(2004).The human tumour suppressor CEACAM1 modulates apoptosis and is implicated in early colorectal tumorigenesis.Oncogene,23,9306-9313.
14. Nollau, P.,Scheller, H.,Kona-Horstmann, M.,Rohde, S.,Hagenmuller, F.,Wagener, C.,Neumaier, M.(1997).Expression of CD66a (human C-CAM) and other members of the carcinoembryonic antigen gene family of adhesion molecules in human colorectal adenomas.Cancer Res.,57,2354-2357.
15. Riethdorf, L.,Lisboa, B.W.,Henkel, U.,Naumann, M.,Wagener, C.,Löning, T.(1997).Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland.J. Histochem. Cytochem.,45,957-963.
16. Sienel, W.,Dango, S.,Woelfle, U.,Morresi-Hauf, A.,Wagener, C.,Brümmer, J.,Mutschler, W.,Passlick, B.,Pantel, K.(2003).Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes progression of non-small cell lung cancer.Clin. Cancer Res.,9,2260-2266.
17. Soslow, R.A.,Dannenberg, A.J.,Rush, D.,Woerner, B.M.,Khan, K.N.,Masferrer, J.,Koki, A.T.(2000).COX-2 is expressed in human pulmonary, colonic, and mammary tumors.Cancer,89,2637-2645.
18. Thies, A.,Moll, I.,Berger, J.,Wagener, C.,Brummer, J.,Schulze, H.J.,Brunner, G.,Schumacher, U.(2002).CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease.J. Clin. Oncol.,20,2530-2536.
19. Thöm, I.,Schult-kronefeld, O.,Burkholder, I.,Schuch, G.,Andritzky, B.,Kastendieck, H.,Edler, L.,Wagener, C.,Bokemeyer, C.,Schumacher, U.,Lacck, E.(2009).Expression of CEACAM1 in pulmonary adenocarcinomas and their metastases.Anticancer Res.,29,249-254.
20. Tilki, D.,Irmak, S.,Oliveira-Ferrer, L.,Hauschild, J.,Miethe, K.,Atakaya, H.,Hammerer, P.,Friedrich, M.G.,Schuch, G.,Galalae, R.,Stief, C.G.,Kilic, E.,Huland, H.,Ergun, S.(2006).CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer.Oncogene,25,4965-4974.
21. Tilki, D.,Oliveira-Ferrer, L.,Kilic, N.,Friedrich, M.G.,Stief, C.G.,Ergun, S.(2007).One molecule, two faces. Epithelial loss of cell adhesion molecule CEACAM1 activates angiogenesis in Bladder and prostate cancer.Urologe A.,46,1128-1134.
22. Volpert, O.,Luo, W.,Liu, T.J.,Estrera, V.T.,Logothetis, C.,Lin, S.H.(2002).Inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1.J. Biol. Chem.,277,35696-35702.
23. Zhou, C.J.,Qu, X.,Yang, Y.M.,Wang, F.F.,Dong, Z.Q.,Wang, C.Q.,Zhang, X.Y.,Liu, G.X.,Wei, F.C.,Sun, S.Z.(2009).CEACAM1 distribution and it's effects on angiogenesis and lymphangiogenesis in oral carcinoma.Oral Oncol.,45,883-886.

1. Zhang, Jie,Zhang, Jiao,Yu, Chao,Yao, Sihong,Yang, Xiaomeng,Tang, Peizhi,Tan, Dunyong,Nie, Xi,Mamat, Zulbnur,Li, Zhongzheng,Jiang, Huang,Huang, Jianjun(2015).Histone 3 Trimethylation of IGFBP-7 Gene Promoter by Expression of D5 Stat5a in Breast Epithelial Cells.中國生理學雜誌,58(5),275-284.
2. Zhao, Song,Zhang, Kai,Wang, Yongmei,Wang, Jianli,Wang, Huimin,Ma, Rong,Liu, Yanhong,Liang, Weili,Gao, Haidong,Gai, Xiaodong(2015).Diagnostic Values of Carcinoembryonic Antigen, Cancer Antigen 15-3 and Cancer Antigen 125 Levels in Nipple Discharge.中國生理學雜誌,58(6),385-392.