Dynamic expression of CEACAM7 in precursor lesions of gastric carcinoma and its prognostic value in combination with CEA

World Journal of Surgical Oncology

Yichao Feng¹  Daiming Fan²  Yongzhan Nie²  Kai Li²  Yong Gu²  Liyun Zhang¹  Jinfeng Zhou² 

[1]Department of Digestive Diseases, Affiliated Hospital of Yan'an University, Yan'an, 716000, China

[2]State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Number 15, Changle Western Road, Xi'an,710032 China

关键词: CEA;    prognosis;    precursor lesions;    gastric carcinoma;    CEACAM7;   

Others  :  1206580
DOI  :  10.1186/1477-7819-9-172

 received in 2011-08-08, accepted in 2011-12-23,  发布年份 2011

【 摘 要 】

Background

The significance of carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) expression in gastric carcinoma and precancerous lesions and its correlation with CEA expression has rarely been previously investigated.

Methods

CEACAM7 and CEA expression was detected by immunohistochemistry in consecutive sections of 345 subjects with gastric carcinoma and precancerous lesions. Laser confocal analysis was performed to determine CEACAM7 and CEA localization. Correlation between CEACAM7 and CEA expression with clinicopathological parameters was statistically analyzed.

Results

CEACAM7 expression correlated with pathologic grading (P = 0.006), Lauren's classification (P = 0.023), and CEA expression (Spearman R = 0.605, P < 0.001) in gastric carcinoma. CEACAM7 co-localized with CEA predominantly in the cytoplasmic membrane of cancerous cells. CEA expression was correlated with lymph node metastasis (P = 0.031). CEACAM7 and CEA expression increased progressively from precursor lesions to gastric carcinomas. A combination of CEACAM7 and CEA expression was determined to be an independent predictor for patients with gastric carcinoma by multivariate analysis (P = 0.001).

Conclusions

CEACAM7 expression correlates with tumor differentiation and CEA expression in gastric carcinoma. CEACAM7 and CEA expression may synergistically promote gastric carcinogenesis. Combined CEACAM7 and CEA expression analysis can be a useful postoperative predictor for patients with gastric carcinoma.

【 授权许可】

   
2011 Zhou et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Lauren P: The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histoclinical classification. Acta Pathol Microbiol Scand 1965, 64:31-49.
• [2]Endoh Y, Sakata K, Tamura G, Ohmura K, Ajioka Y, Watanabe H, Motoyama T: Cellular phenotypes of differentiated-type carcinomas and precancerous lesions of the stomach are dependent on the genetic pathways. J Pathol 2000, 191:257-263.
• [3]Correa P: Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 1995, 19(Suppl 1):S37-S43.
• [4]Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Fléjou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H: The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000, 47:251-255.
• [5]Stanley RH, Aaltonen LA: Pathology and Genetics of Tumours of the Digestive System World Health Organization Classification of Tumours. IARC Press: Lyon; 2000.
• [6]Ikeda Y, Mori M, Kamakura T, Haraguchi Y, Saku M, Sugimachi K: Increased incidence of undifferentiated type of gastric cancer with tumor progression in 912 patients with early gastric cancer and 1245 with advanced gastric cancer. Cancer 1994, 73:2459-63.
• [7]Ohkura Y: Histological diversity of early gastric carcinoma. In The diversity of gastric carcinoma: pathogenesis, diagnosis, and therapy. Edited by Kaminishi M. Tokyo, Japan: Springer-Verlag Press; 2005:117-25.
• [8]Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES: Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999, 286:531-53.
• [9]Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumors. Nature 2000, 406:747-52.
• [10]Ramaswamy S, Tamayo P, Rifkin R, Mukherjee S, Yeang CH, Angelo M, Ladd C, Reich M, Latulippe E, Mesirov JP, Poggio T, Gerald W, Loda M, Lander ES, Golub TR: Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA 2001, 98:15149-54.
• [11]Scholzel S, Zimmermann W, Schwarzkopf G, Grunert F, Rogaczewski B, Thompson J: Carcinoembryonic antigen family members CEACAM6 and CEACAM7 are differentially expressed in normal tissues and oppositely deregulated in hyperplastic colorectal polyps and early adenomas. Am J Pathol 2000, 156:595-605.
• [12]Hashino J, Fukuda Y, Oikawa S, Nakazato H, Nakanishi T: Metastatic potential of human colorectal carcinoma SW1222 cells transfected with cDNA encoding carcinoembryonic antigen. Clin Exp Metastasis 1994, 12:324-8.
• [13]Thompson J, Zimmermann W, Nollau P, Neumaier M, Weber-Arden J, Schrewe H, Craig I, Willcocks T: CGM2, a member of the carcinoembryonic antigen gene family is down-regulated in colorectal carcinomas. J Biol Chem 1994, 30:32924-31.
• [14]Ballesta AM, Molina R, Filella X, Jo J, Gimenez N: Carcinoembryonic antigen in staging and follow-up of patients with solid tumors. Tumour Biol 1995, 16:32-41.
• [15]Maxwell P: Carcinoembryonic antigen: cell adhesion molecule and useful diagnostic marker. Br J Biomed Sci 1999, 56:209-214.
• [16]Jantscheff P, Terracciano L, Lowy A, Glatz-Krieger K, Grunert F, Micheel B, Brümmer J, Laffer U, Metzger U, Herrmann R, Rochlitz C: Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. J Clin Oncol 2003, 21:3638-3646.
• [17]Minton JP, Hoehn JL, Gerber DM: Results of a 400 patients CEA second-look colorectal cancer study. Cancer 1985, 55:1284-1290.
• [18]Wanebo HJ, Llaneras M, Martin T, Kaiser D: Prospective monitoring trial for carcinoma of colon and rectum after surgical resection. Surg Gynecol Obstet 1989, 169:479-487.
• [19]Cardoso ML, Fernandes LC, Kim SB, Matos D: Relationship between peripheral and mesenteric serum levels of CEA and CA 242 with staging and histopathological variables in colorectal carcinoma. Acta Cir Bras 2009, 24:405-10.
• [20]Shively JE, Beatty JD: CEA-related antigens: molecular biology and clinical significance. Crit Rev Oncol Hematol 1985, 2:355-99.
• [21]Kinugasa T, Kuroki M, Takeo H, Matsuo Y, Ohshima K, Yamashita Y, Shirakusa T, Matsuoka Y: Expression of four CEA family antigens (CEA, NCA, BGP and CGM2) in normal and cancerous gastric epithelial cells: up-regulation of BGP and CGM2 in carcinomas. Int J Cancer 1998, 76:148-53.
• [22]Hamilton SR, Aaltonen LA: WHO classification of tumours: Pathology and genetics of tumours of the digestive system. IARC Press: Lyon; 2000.
• [23]Kononen J, Bubendorf L, Kallioniemi A, Bärlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high- throughput molecular profiling of tumor specimens. Nat Med 1998, 4:844-7.
• [24]Wittekind C, Wachner R, Henke W, von Kleist S: Localization of CEA, HCG, lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin in gastric cancer and prognosis. Virchows Arch A Pathol Anat Histopathol 1986, 409:715-24.
• [25]Cardoso ML, Fernandes LC, Kim SB, Matos D: Relationship between peripheral and mesenteric serum levels of CEA and CA 242 with staging and histopathological variables in colorectal carcinoma. Acta Cir Bras 2009, 24:405-10.
• [26]Ivankovics IG, Fernandes LC, Saad SS, Matos D: Peripheral and mesenteric serum levels of CEA and cytokeratins, staging and histopathological variables in colorectal carcinoma. World J Gastroenterol 2008, 14:6699-703.c.
• [27]Chan CH, Camacho-Leal P, Stanners CP: Colorectal Hyperplasia and Dysplasia Due to Human Carcinoembryonic Antigen (CEA) Family Member Expression in Transgenic Mice. PLoS ONE 2007, 2:e1353.
• [28]Degner LF, Kristjanson LJ, Bowman D, Sloan JA, Carriere KC, O'Neil J, Bilodeau B, Watson P, Mueller B: Information needs and decisional preferences in women with breast cancer. JAMA 1997, 277:1485-1492.
• [29]Glare P, Virik K, Jones M, Hudson M, Eychmuller S, Simes J, Christakis N: A systematic review of physicians' survival predictions in terminally ill cancer patients. Br Med J 2003, 327:195.
• [30]Caprioli RM: Deciphering Protein Molecular Signatures in Cancer Tissues to Aid in Diagnosis, Prognosis, and Therapy. Cancer Res 2005, 65:10642-10645.