Advertisement

Annals of Surgical Oncology

, Volume 23, Issue 4, pp 1244–1251 | Cite as

Prognostic Significance of Carcinoembryonic Antigen Staining in Cancer Tissues of Gastric Cancer Patients

  • Wei Wang
  • Sharvesh Raj Seeruttun
  • Cheng Fang
  • Jiewei Chen
  • Yong Li
  • Zhimin Liu
  • Youqing Zhan
  • Wei Li
  • Yingbo Chen
  • Xiaowei Sun
  • Yuanfang Li
  • Dazhi Xu
  • Yuanxiang Guan
  • Zhiwei ZhouEmail author
Gastrointestinal Oncology

Abstract

Purpose

The aim of this study was to assess the significance of the correlation among tissue carcinoembryonic antigen (CEA) expression with serum CEA (sCEA) levels and long-term survival to highlight the clinical prognostic significance of tissue CEA expression in gastric cancer patients.

Methods

Immunohistological method and radioimmunoassay were used to assess tissue and sCEA expression, respectively. Univariate and multivariate analyses were performed to determine correlations, and the Kaplan–Meier method was used to investigate the prognostic significance.

Results

Our results demonstrate that tissue CEA in gastric cancer is significantly correlated with preoperative sCEA levels (p = 0.031), depth of invasion (p = 0.001), lymph node metastasis (p < 0.001), distant metastasis (p = 0.001), and TNM staging (p < 0.001). The 5-year survival rates were 67.6, 53.9, and 40.1 % for negatively, moderately, and intensely positively stained tissues (p < 0.001), and 57.0 and 37.9 % for serum with normal and elevated CEA expression (p = 0.031). Multivariate analysis revealed that tissue CEA can be considered an independent prognostic factor. Further analysis illustrated that patients with negative expression in both tissue and serum had better prognosis compared with those positively expressing CEA in both tissue and serum and/or those positively expressing CEA in either tissue or serum (p < 0.001). Our results also demonstrated that patients with negative tissue CEA staining and elevated sCEA expression had a better 5-year survival.

Conclusion

Tissue CEA expression in gastric cancer is directly correlated with sCEA levels and long-term prognosis. Thus, tissue CEA expression can be considered as a useful biomarker to improve the interpretation of sCEA levels in predicting long-term survival.

Keywords

Gastric Cancer Gastric Cancer Cell Gastric Cancer Patient Gastric Cancer Tissue sCEA Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

Work on this article was supported in part by the National Natural Science Foundation of China (Grant Nos. 81172080, 81201773, and 81411130217), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120171120114), the Science and Technology Projects of Guangdong Province (Grant No. 2011B031800181), and the National High-Tech R&D Program [863 Program] (Grant No. 2012AA02A504).

Disclosures

Wei Wang, Sharvesh Raj Seeruttun, Cheng Fang, Jiewei Chen, Yong Li, Zhimin Liu, Youqing Zhan, Wei Li, Yingbo Chen, Xiaowei Sun, Yuanfang Li, Dazhi Xu, Yuanxiang Guan, and Zhiwei Zhou have no conflicts or financial interests to be declared.

References

  1. 1.
    Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.CrossRefPubMedGoogle Scholar
  2. 2.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMedGoogle Scholar
  3. 3.
    Lim JS, Yun MJ, Kim MJ, et al. CT and PET in stomach cancer: preoperative staging and monitoring of response to therapy. Radiographics. 2006;26(1):143–56.CrossRefPubMedGoogle Scholar
  4. 4.
    Posner MR, Mayer RJ. The use of serologic tumor markers in gastrointestinal malignancies. Hematol Oncol Clin N Am. 1994;8(3):533–53.Google Scholar
  5. 5.
    Takahashi Y, Takeuchi T, Sakamoto J, et al. The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study. Gastric Cancer. 2003;6(3):142–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Thompson J, Zimmermann W, Osthus-Bugat P, et al. Long-range chromosomal mapping of the carcinoembryonic antigen (CEA) gene family cluster. Genomics. 1992;12(4):761–72.CrossRefPubMedGoogle Scholar
  7. 7.
    Tamada R, Hiramoto Y, Tsujitani S, et al. Serum CEA levels facilitate detection of recurrences of cancer in patients after gastrectomy. Jpn J Surg. 1985;15(1):23–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Park SH, Ku KB, Chung HY, Yu W. Prognostic significance of serum and tissue carcinoembryonic antigen in patients with gastric adenocarcinomas. Cancer Res Treat. 2008;40(1):16–21.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bhatnagar J, Heroman W, Murphy M, Austin GE. Immunohistochemical detection of carcinoembryonic antigen in esophageal carcinomas: a comparison with other gastrointestinal neoplasms. Anticancer Res. 2002;22(3):1849–57.PubMedGoogle Scholar
  10. 10.
    Nazato DM, Matos LL, Waisberg DR, Souza JR, Martins LC, Waisberg J. Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma. Arq Gastroenterol. 2009;46(1):26–31.CrossRefPubMedGoogle Scholar
  11. 11.
    Okamura A, Ohkawa J, Fujisawa H, Sashikata T. Clinicopathological study on the relationship between serum-CEA and tissue-CEA of resected lung cancer cases. Acta Pathol Jpn. 1984;34(6):1209–19.PubMedGoogle Scholar
  12. 12.
    Michaelidou K, Tzovaras A, Missitzis I, Ardavanis A, Scorilas A. The expression of the CEACAM19 gene, a novel member of the CEA family, is associated with breast cancer progression. Int J Oncol. 2013;42(5):1770–77.PubMedGoogle Scholar
  13. 13.
    Han CP, Lee MY, Kok LF, et al. A reappraisal of three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR), and five-marker (ER/Vim/CEA/PR/p16INK4a) panels in the diagnostic distinction between primary endocervical and endometrial adenocarcinomas in a tissue microarray study. Arch Gynecol Obstet. 2010;281(5):845–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Smithson JE, Warren BF, Young S, Pigott R, Jewell DP. Heterogeneous expression of carcinoembryonic antigen in the normal colon and upregulation in active ulcerative colitis. J Pathol. 1996;180(2):146–51.CrossRefPubMedGoogle Scholar
  15. 15.
    Isaacson P, Judd MA. Carcinoembryonic antigen (CEA) in the normal human small intestine: a light and electron microscopic study. Gut. 1977;18(10):786–91.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bunn PA Jr, Cohen MI, Widerlite L, Nugent JL, Matthews MJ, Minna JD. Simultaneous gastric and plasma immunoreactive plasma carcinoembryonic antigen in 108 patients undergoing gastroscopy. Gastroenterology. 1979;76(4):734–41.PubMedGoogle Scholar
  17. 17.
    Charalabopoulos K, Kotsalos A, Batistatou A, et al. Serum and tissue selenium levels in gastric cancer patients and correlation with CEA. Anticancer Res. 2009;29(8):3465–67.PubMedGoogle Scholar
  18. 18.
    Kojima O, Ikeda E, Uehara Y, Majima T, Fujita Y, Majima S. Correlation between carcinoembryonic antigen in gastric cancer tissue and survival of patients with gastric cancer. Gan. 1984;75(3):230–36.PubMedGoogle Scholar
  19. 19.
    Nishida H. Immunohistochemical localization of carcinoembryonic antigen (CEA) in gastric cancer–a comparative study between tissue CEA and plasma CEA [in Japanese]. Nihon Geka Gakkai Zasshi. 1983;84(4):328–35.PubMedGoogle Scholar
  20. 20.
    Rosandić-Pilas M, Hadzic N, Stavljenic A, Juricic M, Scukanec-Spoljar M. Relationship between tissue and serum concentrations of carcinoembryonic antigen (CEA) in gastric and colonic carcinomas. Acta Med Austriaca. 1990;17(5):89–93.PubMedGoogle Scholar
  21. 21.
    Lee JC, Lee SY, Kim CY, Yang DH. Clinical utility of tumor marker cutoff ratio and a combination scoring system of preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4 levels in gastric cancer. J Korean Surg Soc. 2013;85(6):283–89.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhou H, Stanners CP, Fuks A. Specificity of anti-carcinoembryonic antigen monoclonal antibodies and their effects on CEA-mediated adhesion. Cancer Res. 1993;53(16):3817–22.PubMedGoogle Scholar
  23. 23.
    Beauchemin N, Draber P, Dveksler G, et al. Redefined nomenclature for members of the carcinoembryonic antigen family. Exp Cell Res. 1999;252(2):243–49.CrossRefPubMedGoogle Scholar
  24. 24.
    Bjerner J, Lebedin Y, Bellanger L, et al. Protein epitopes in carcinoembryonic antigen. Report of the ISOBM TD8 workshop. Tumour Biol. 2002;23(4):249–62.CrossRefPubMedGoogle Scholar
  25. 25.
    Chiquillo Barber MT, Bort Marti I, Navarro Fos S, Perez Bacete M, Esclapez Valero J, Gomez-Ferrer Bayo F. A correlation between serum levels of preoperative CEA and CEA immunohistochemical staining in colorectal carcinoma [in Spanish]. Rev Esp Enferm Dig. 1993;83(4):249–54.PubMedGoogle Scholar
  26. 26.
    Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9(2):67–81.CrossRefPubMedGoogle Scholar
  27. 27.
    Burtin P, von Kleist S, Sabine MC, King M. Immunohistological localization of carcinoembryonic antigen and nonspecific cross-reacting antigen in gastrointestinal normal and tumoral tissues. Cancer Res. 1973;33(12):3299–305.PubMedGoogle Scholar
  28. 28.
    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(10):2459–63.CrossRefPubMedGoogle Scholar
  29. 29.
    Kodera Y, Isobe K, Yamauchi M, et al. Expression of carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in gastrointestinal cancer; the correlation with degree of differentiation. Br J Cancer. 1993;68(1):130–36.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Imamura T, Komatsu S, Ichikawa D, et al. Poor prognostic subgroup in T3N0 stage IIA gastric cancer, suggesting an indication for adjuvant chemotherapy. J Surg Oncol. 2015;111(2):221–25.CrossRefPubMedGoogle Scholar
  31. 31.
    Takahari D, Hamaguchi T, Yoshimura K, et al. Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer. Gastric Cancer. 2014;17(2):383–386.CrossRefPubMedGoogle Scholar
  32. 32.
    Min C, Bangalore S, Jhawar S, et al. Chemoradiation therapy versus chemotherapy alone for gastric cancer after R0 surgical resection: a meta-analysis of randomized trials. Oncology. 2014;86(2):79–85.CrossRefPubMedGoogle Scholar
  33. 33.
    Stessin AM, Sison C, Schwartz A, Ng J, Chao CK, Li B. Does adjuvant radiotherapy benefit patients with diffuse-type gastric cancer? Results from the surveillance, epidemiology, and end results database. Cancer. 2014;120(22):3562–68.CrossRefPubMedGoogle Scholar
  34. 34.
    Foo M, Crosby T, Rackley T, Leong T. Role of (chemo)-radiotherapy in resectable gastric cancer. Clin Oncol (R Coll Radiol). 2014;26(9):541–50.CrossRefPubMedGoogle Scholar
  35. 35.
    Lordick F, Lorenzen S, Yamada Y, Ilson D. Optimal chemotherapy for advanced gastric cancer: is there a global consensus? Gastric Cancer. 2014;17(2):213–25.CrossRefPubMedGoogle Scholar
  36. 36.
    Oh DY, Bang YJ. Adjuvant and neoadjuvant therapy for gastric cancer. Curr Treat Options Oncol. 2013;14(3):311–20.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Wei Wang
    • 1
    • 2
  • Sharvesh Raj Seeruttun
    • 1
    • 2
  • Cheng Fang
    • 1
    • 2
  • Jiewei Chen
    • 1
    • 3
  • Yong Li
    • 1
    • 3
  • Zhimin Liu
    • 1
    • 2
  • Youqing Zhan
    • 1
    • 2
  • Wei Li
    • 1
    • 2
  • Yingbo Chen
    • 1
    • 2
  • Xiaowei Sun
    • 1
    • 2
  • Yuanfang Li
    • 1
    • 2
  • Dazhi Xu
    • 1
    • 2
  • Yuanxiang Guan
    • 1
    • 2
  • Zhiwei Zhou
    • 1
    • 2
    Email author
  1. 1.State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouChina
  2. 2.Department of Gastric and Pancreatic SurgerySun Yat-sen University Cancer CenterGuangzhouChina
  3. 3.Department of PathologySun Yat-sen University Cancer CenterGuangzhouChina

Personalised recommendations