Serological Markers of Digestive Tract Cancers

  • Jorge L. SepulvedaEmail author
Part of the Molecular Pathology Library book series (MPLB, volume 7)


Serum protein biomarkers offer the potential to diagnose and monitor GI tumors with simple, quantitative, easily automated, and inexpensive assays. Unfortunately the diagnostic accuracy of current and most prospective markers is insufficient to recommend their use in isolation for tumor detection, especially in the general population. In contrast, the role of serum protein markers in monitoring the response to treatment is well accepted, particularly for the Carcinoembryonic Antigen (CEA) in colorectal cancer. Other glycoprotein markers, such as CA19-9 and CA242, have shown some value, particularly in combination with CEA, in detecting and monitoring advanced GI cancers. The list of newer, potential markers is large and likely to expand at an increasing rate, especially in consequence of large-scale “omic” approaches. While comprehensive proteomic approaches are unlikely to be used in the near future, combinatorial panels of selected markers offering increased sensitivity and specificity are expected to replace single biomarkers in the evaluation of patients with GI tumors.


Cytosine Deaminase Medullary Thyroid Carcinomas115 Thermal Lens Microscopy Tumor Marker Measurement Serum Protein Marker 
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.


  1. 1.
    Bonfrer JM. Working Group on Tumor Marker Criteria (WGTMC). Tumour Biol. 1990;11(5):287–288.PubMedCrossRefGoogle Scholar
  2. 2.
    Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121:439–462.PubMedCrossRefGoogle Scholar
  3. 3.
    Zebhauser R, Kammerer R, Eisenried A, McLellan A, Moore T, Zimmermann W. Identification of a novel group of evolutionarily conserved members within the rapidly diverging murine Cea family. Genomics. 2005;86(5):566–580.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Naghibalhossaini F, Ebadi P. Evidence for CEA release from human colon cancer cells by an endogenous GPI-PLD enzyme. Cancer Lett. 2006;234(2):158–167.PubMedCrossRefGoogle Scholar
  6. 6.
    Pakdel A, Naghibalhossaini F, Mokarram P, Jaberipour M, Hosseini A. Regulation of carcinoembryonic antigen release from colorectal cancer cells. Mol Biol Rep. 2012;39:3695–3704.PubMedCrossRefGoogle Scholar
  7. 7.
    Bjerner J, Lebedin Y, Bellanger L, et al. Protein epitopes in carcinoembryonic antigen. Report of the ISOBM TD8 workshop. Tumour Biol. 2002;23(4):249–262.PubMedCrossRefGoogle Scholar
  8. 8.
    Huang JQ, Turbide C, Daniels E, Jothy S, Beauchemin N. Spatiotemporal expression of murine carcinoembryonic antigen (CEA) gene family members during mouse embryogenesis. Development. 1990;110(2):573–588.PubMedGoogle Scholar
  9. 9.
    Zimmermann W, Ortlieb B, Friedrich R, von Kleist S. Isolation and characterization of cDNA clones encoding the human carcinoembryonic antigen reveal a highly conserved repeating structure. Proc Natl Acad Sci USA. 1987;84(9):2960–2964.PubMedCrossRefGoogle Scholar
  10. 10.
    Sanders DS, Wilson CA, Bryant FJ, et al. Classification and localisation of carcinoembryonic antigen (CEA) related antigen expression in normal oesophageal squamous mucosa and squamous carcinoma. Gut. 1994;35(8):1022–1025.PubMedCrossRefGoogle Scholar
  11. 11.
    Sanders DS, Stocks SC, Milne DM, Milne GA, Hopwood D, Kerr MA. Membranous expression of carcinoembryonic antigen (CEA) in the normal cervical squamous mucosa. J Pathol. 1992;167(1):77–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Savino W, Durand D, Dardenne M. Immunohistochemical evidence for the expression of the carcinoembryonic antigen by human thymic epithelial cells in vitro and in neoplastic conditions. Am J Pathol. 1985;121(3):418–425.PubMedGoogle Scholar
  13. 13.
    Nouwen EJ, Pollet DE, Eerdekens MW, Hendrix PG, Briers TW, De Broe ME. Immunohistochemical localization of placental alkaline phosphatase, carcinoembryonic antigen, and cancer antigen 125 in normal and neoplastic human lung. Cancer Res. 1986;46(2):866–876.PubMedGoogle Scholar
  14. 14.
    Metze D, Luger TA. Ultrastructural localization of carcinoembryonic antigen (CEA) glycoproteins and epithelial membrane antigen (EMA) in normal and neoplastic sweat glands. J Cutan Pathol. 1996;23(6):518–529.PubMedCrossRefGoogle Scholar
  15. 15.
    Nyati MK, Sreekumar A, Li S, et al. High and selective expression of yeast cytosine deaminase under a carcinoembryonic antigen promoter-enhancer. Cancer Res. 2002;62(8):2337–2342.PubMedGoogle Scholar
  16. 16.
    Zhang G, Liu T, Chen YH, et al. Tissue specific cytotoxicity of colon cancer cells mediated by nanoparticle-delivered suicide gene in vitro and in vivo. Clin Cancer Res. 2009;15(1):201–207.PubMedCrossRefGoogle Scholar
  17. 17.
    Dabrowska A, Szary J, Kowalczuk M, Szala S, Ugorski M. CEA-negative glioblastoma and melanoma cells are sensitive to cytosine deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen promoter. Acta Biochim Pol. 2004;51(3):723–732.PubMedGoogle Scholar
  18. 18.
    Han SU, Kwak TH, Her KH, et al. CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling. Oncogene. 2008;27(5):675–683.PubMedCrossRefGoogle Scholar
  19. 19.
    Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K. Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J Biol Chem. 2008;283(23):15647–15655.PubMedCrossRefGoogle Scholar
  20. 20.
    Baranov V, Hammarstrom S. Carcinoembryonic antigen (CEA) and CEA-related cell adhesion molecule 1 (CEACAM1), apically expressed on human colonic M cells, are potential receptors for microbial adhesion. Histochem Cell Biol. 2004;121(2):83–89.PubMedCrossRefGoogle Scholar
  21. 21.
    Screaton RA, Penn LZ, Stanners CP. Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation. J Cell Biol. 1997;137(4):939–952.PubMedCrossRefGoogle Scholar
  22. 22.
    Naghibalhossaini F, Yoder AD, Tobi M, Stanners CP. Evolution of a tumorigenic property conferred by glycophosphatidyl-inositol membrane anchors of carcinoembryonic antigen gene family members during the primate radiation. Mol Biol Cell. 2007;18(4):1366–1374.PubMedCrossRefGoogle Scholar
  23. 23.
    Ilantzis C, DeMarte L, Screaton RA, Stanners CP. Deregulated expression of the human tumor marker CEA and CEA family member CEACAM6 disrupts tissue architecture and blocks colonocyte differentiation. Neoplasia. 2002;4(2):151–163.PubMedCrossRefGoogle Scholar
  24. 24.
    Baranov V, Yeung MM, Hammarstrom S. Expression of carcinoembryonic antigen and nonspecific cross-reacting 50-kDa antigen in human normal and cancerous colon mucosa: comparative ultrastructural study with monoclonal antibodies. Cancer Res. 1994;54(12):3305–3314.PubMedGoogle Scholar
  25. 25.
    Leusch HG, Drzeniek Z, Markos-Pusztai Z, Wagener C. Binding of Escherichia coli and Salmonella strains to members of the carcinoembryonic antigen family: differential binding inhibition by aromatic alpha-glycosides of mannose. Infect Immun. 1991;59(6):2051–2057.PubMedGoogle Scholar
  26. 26.
    Allez M, Brimnes J, Shao L, Dotan I, Nakazawa A, Mayer L. Activation of a unique population of CD8(+) T cells by intestinal epithelial cells. Ann N Y Acad Sci. 2004;1029:22–35.PubMedCrossRefGoogle Scholar
  27. 27.
    Prado IB, Laudanna AA, Carneiro CR. Susceptibility of colorectal-carcinoma cells to natural-killer-mediated lysis: relationship to CEA expression and degree of differentiation. Int J Cancer. 1995;61(6):854–860.PubMedCrossRefGoogle Scholar
  28. 28.
    Kammerer R, von Kleist S. CEA expression of colorectal adenocarcinomas is correlated with their resistance against LAK-cell lysis. Int J Cancer. 1994;57(3):341–347.PubMedCrossRefGoogle Scholar
  29. 29.
    Kammerer R, Zimmermann W. Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families. BMC Biol. 2010;8:12.PubMedCrossRefGoogle Scholar
  30. 30.
    Hostetter RB, Augustus LB, Mankarious R, et al. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Natl Cancer Inst. 1990;82(5):380–385.PubMedCrossRefGoogle Scholar
  31. 31.
    Jessup JM, Thomas P. Carcinoembryonic antigen: function in metastasis by human colorectal carcinoma. Cancer Metastasis Rev. 1989;8(3):263–280.PubMedCrossRefGoogle Scholar
  32. 32.
    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(12):e1353.PubMedCrossRefGoogle Scholar
  33. 33.
    Leung N, Turbide C, Olson M, Marcus V, Jothy S, Beauchemin N. Deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1) gene contributes to colon tumor progression in a murine model of carcinogenesis. Oncogene. 2006;25(40):5527–5536.PubMedCrossRefGoogle Scholar
  34. 34.
    Leung N, Turbide C, Balachandra B, Marcus V, Beauchemin N. Intestinal tumor progression is promoted by decreased apoptosis and dysregulated Wnt signaling in Ceacam1−/− mice. Oncogene. 2008;27(36):4943–4953.PubMedCrossRefGoogle Scholar
  35. 35.
    Song JH, Cao Z, Yoon JH, et al. Genetic alterations and expression pattern of CEACAM1 in colorectal adenomas and cancers. Pathol Oncol Res. 2011;17:67–74.PubMedCrossRefGoogle Scholar
  36. 36.
    Jessup JM, Samara R, Battle P, Laguinge LM. Carcinoembryonic antigen promotes tumor cell survival in liver through an IL-10-dependent pathway. Clin Exp Metastasis. 2004;21(8):709–717.PubMedCrossRefGoogle Scholar
  37. 37.
    Minami S, Furui J, Kanematsu T. Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. Cancer Res. 2001;61(6):2732–2735.PubMedGoogle Scholar
  38. 38.
    Gangopadhyay A, Lazure DA, Thomas P. Adhesion of colorectal carcinoma cells to the endothelium is mediated by cytokines from CEA stimulated Kupffer cells. Clin Exp Metastasis. 1998;16(8):703–712.PubMedCrossRefGoogle Scholar
  39. 39.
    Samara RN, Laguinge LM, Jessup JM. Carcinoembryonic antigen inhibits Anoikis in colorectal carcinoma cells by interfering with trail-R2 (DR5) signaling. Cancer Res. 2007;67(10):4774–4782.PubMedCrossRefGoogle Scholar
  40. 40.
    Camacho-Leal P, Zhai AB, Stanners CP. A co-clustering model involving alpha5beta1 integrin for the biological effects of GPI-anchored human carcinoembryonic antigen (CEA). J Cell Physiol. 2007;211(3):791–802.PubMedCrossRefGoogle Scholar
  41. 41.
    Ordonez C, Zhai AB, Camacho-Leal P, Demarte L, Fan MM, Stanners CP. GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction. J Cell Physiol. 2007;210(3):757–765.PubMedCrossRefGoogle Scholar
  42. 42.
    Camacho-Leal P, Stanners CP. The human carcinoembryonic antigen (CEA) GPI anchor mediates anoikis inhibition by inactivation of the intrinsic death pathway. Oncogene. 2008;27(11):1545–1553.PubMedCrossRefGoogle Scholar
  43. 43.
    Wirth T, Soeth E, Czubayko F, Juhl H. Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth. Clin Exp Metastasis. 2002;19(2):155–160.PubMedCrossRefGoogle Scholar
  44. 44.
    Soeth E, Wirth T, List HJ, et al. Controlled ribozyme targeting demonstrates an antiapoptotic effect of carcinoembryonic antigen in HT29 colon cancer cells. Clin Cancer Res. 2001;7(7):2022–2030.PubMedGoogle Scholar
  45. 45.
    Sharkey RM, Karacay H, Vallabhajosula S, et al. Metastatic human colonic carcinoma: molecular imaging with pretargeted SPECT and PET in a mouse model. Radiology. 2008;246(2):497–507.PubMedCrossRefGoogle Scholar
  46. 46.
    Aarts F, Boerman OC, Sharkey RM, et al. Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab′)2 antibody. Cancer. 2010;116(4 Suppl):1111–1117.PubMedCrossRefGoogle Scholar
  47. 47.
    Kaushal S, McElroy MK, Luiken GA, et al. Fluorophore-conjugated anti-CEA antibody for the intraoperative imaging of pancreatic and colorectal cancer. J Gastrointest Surg. 2008;12(11):1938–1950.PubMedCrossRefGoogle Scholar
  48. 48.
    Hong H, Sun J, Cai W. Radionuclide-based cancer imaging targeting the carcinoembryonic antigen. Biomark Insights. 2008;3:435–451.PubMedGoogle Scholar
  49. 49.
    Park S, Lee B, Kim I, et al. Immunobead RT-PCR versus regular RT-PCR amplification of CEA mRNA in peripheral blood. J Cancer Res Clin Oncol. 2001;127(8):489–494.PubMedCrossRefGoogle Scholar
  50. 50.
    Douard R, Moutereau S, Serru V, et al. Immunobead multiplex RT-PCR detection of carcinoembryonic genes expressing cells in the blood of colorectal cancer patients. Clin Chem Lab Med. 2005;43(2):127–132.PubMedCrossRefGoogle Scholar
  51. 51.
    Liu Z, Jin C, Yu Z, et al. Radioimmunotherapy of human colon cancer xenografts with 131I-labeled anti-CEA monoclonal antibody. Bioconjug Chem. 2010;21(2):314–318.PubMedCrossRefGoogle Scholar
  52. 52.
    Liu Z, Jin C, Yu Z, et al. Radioimmunotherapy of human colon cancer xenografts with 131I-labeled anti-CEA monoclonal antibody. Bioconjug Chem. 2010;21(2):314–318.PubMedCrossRefGoogle Scholar
  53. 53.
    Buchegger F, Roth A, Allal A, et al. Radioimmunotherapy of colorectal cancer liver metastases: combination with radiotherapy. Ann N Y Acad Sci. 2000;910:263–269. discussion 9–70.PubMedCrossRefGoogle Scholar
  54. 54.
    Mori F, Giannetti P, Peruzzi D, et al. A therapeutic cancer vaccine targeting carcinoembryonic antigen in intestinal carcinomas. Hum Gene Ther. 2009;20(2):125–136.PubMedCrossRefGoogle Scholar
  55. 55.
    Ojima T, Iwahashi M, Nakamura M, et al. Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice. Int J Cancer. 2007;120(3):585–593.PubMedCrossRefGoogle Scholar
  56. 56.
    Shibaguchi H, Luo NX, Kuroki M, et al. A fully human chimeric immune receptor for retargeting T-cells to CEA-expressing tumor cells. Anticancer Res. 2006;26(6A):4067–4072.PubMedGoogle Scholar
  57. 57.
    Hou Y, Kavanagh B, Fong L. Distinct CD8+ T cell repertoires primed with agonist and native peptides derived from a tumor-associated antigen. J Immunol. 2008;180(3):1526–1534.PubMedGoogle Scholar
  58. 58.
    Li HJ, Everts M, Pereboeva L, et al. Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter. Cancer Res. 2007;67(11):5354–5361.PubMedCrossRefGoogle Scholar
  59. 59.
    Bos R, van Duikeren S, Morreau H, et al. Balancing between antitumor efficacy and autoimmune pathology in T-cell-mediated targeting of carcinoembryonic antigen. Cancer Res. 2008;68(20):8446–8455.PubMedCrossRefGoogle Scholar
  60. 60.
    Jung HS, Lee SW. Ribozyme-mediated selective killing of cancer cells expressing carcinoembryonic antigen RNA by targeted trans-splicing. Biochem Biophys Res Commun. 2006;349(2):556–563.PubMedCrossRefGoogle Scholar
  61. 61.
    Zamboni S, Mallano A, Flego M, et al. Genetic construction, expression, and characterization of a single chain anti-CEA antibody fused to cytosine deaminase from yeast. Int J Oncol. 2008;32(6):1245–1251.PubMedCrossRefGoogle Scholar
  62. 62.
    Guadagni F, Roselli M, Cosimelli M, et al. Quantitative analysis of CEA expression in colorectal adenocarcinoma and serum: lack of correlation. Int J Cancer. 1997;72(6):949–954.PubMedCrossRefGoogle Scholar
  63. 63.
    Thomson DMP, Krupey J, Freedman SO, Gold P. The radioimmunoassay of Circulating carcinoembryonic antigen of the human digestive system. Proc Natl Acad Sci USA. 1969;64(1):161–167.PubMedCrossRefGoogle Scholar
  64. 64.
    Sato K, Tokeshi M, Kimura H, Kitamori T. Determination of carcinoembryonic antigen in human sera by integrated bead-bed immunoassay in a microchip for cancer diagnosis. Anal Chem. 2001;73(6):1213–1218.PubMedCrossRefGoogle Scholar
  65. 65.
    Hundt S, Haug U, Brenner H. Blood markers for early detection of colorectal cancer: a systematic review. Cancer Epidemiol Biomarkers Prev. 2007;16(10):1935–1953.PubMedCrossRefGoogle Scholar
  66. 66.
    Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624–630.PubMedGoogle Scholar
  67. 67.
    Sturgeon CM, Duffy MJ, Stenman UH, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008;54(12):e11-e79.PubMedCrossRefGoogle Scholar
  68. 68.
    Lim YK, Kam MH, Eu KW. Carcinoembryonic antigen screening: how far should we go? Singapore Med J. 2009;50(9):862–865.PubMedGoogle Scholar
  69. 69.
    Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124(7):979–994.PubMedGoogle Scholar
  70. 70.
    Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP. American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer. 2000;88(7):1739–1757.PubMedCrossRefGoogle Scholar
  71. 71.
    Huh JW, Oh BR, Kim HR, Kim YJ. Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer. J Surg Oncol. 2010;101(5):396–400.PubMedGoogle Scholar
  72. 72.
    Ogata Y, Murakami H, Sasatomi T, et al. Elevated preoperative serum carcinoembrionic antigen level may be an effective indicator for needing adjuvant chemotherapy after potentially curative resection of stage II colon cancer. J Surg Oncol. 2009;99(1):65–70.PubMedCrossRefGoogle Scholar
  73. 73.
    Kievit J. Follow-up of patients with colorectal cancer: numbers needed to test and treat. Eur J Cancer. 2002;38(7):986–999.PubMedCrossRefGoogle Scholar
  74. 74.
    Tan E, Gouvas N, Nicholls RJ, Ziprin P, Xynos E, Tekkis PP. Diagnostic precision of carcinoembryonic antigen in the detection of recurrence of colorectal cancer. Surg Oncol. 2009;18(1):15–24.PubMedCrossRefGoogle Scholar
  75. 75.
    Bruinvels DJ, Stiggelbout AM, Kievit J, van Houwelingen HC, Habbema JD, van de Velde CJ. Follow-up of patients with colorectal cancer. A meta-analysis. Ann Surg. 1994;219(2):174–182.PubMedCrossRefGoogle Scholar
  76. 76.
    Figueredo A, Rumble RB, Maroun J, et al. Follow-up of patients with curatively resected colorectal cancer: a practice guideline. BMC Cancer. 2003;3:26.PubMedCrossRefGoogle Scholar
  77. 77.
    Hida J, Yasutomi M, Shindoh K, et al. Second-look operation for recurrent colorectal cancer based on carcinoembryonic antigen and imaging techniques. Dis Colon Rectum. 1996;39(1):74–79.PubMedCrossRefGoogle Scholar
  78. 78.
    Weiser MR, Landmann RG, Kattan MW, et al. Individualized prediction of colon cancer recurrence using a nomogram. J Clin Oncol. 2008;26(3):380–385.PubMedCrossRefGoogle Scholar
  79. 79.
    Kattan MW, Gonen M, Jarnagin WR, et al. A nomogram for predicting disease-specific survival after hepatic resection for metastatic colorectal cancer. Ann Surg. 2008;247(2):282–287.PubMedCrossRefGoogle Scholar
  80. 80.
    Li M, Li JY, Zhao AL, Gu J. Colorectal cancer or colon and rectal cancer? Clinicopathological comparison between colonic and rectal carcinomas. Oncology. 2007;73(1–2):52–57.PubMedCrossRefGoogle Scholar
  81. 81.
    Chen CH, Hsieh MC, Lai CC, et al. Lead time of carcinoembryonic antigen elevation in the postoperative follow-up of colorectal cancer did not affect the survival rate after recurrence. Int J Colorectal Dis. 2010;25(5):567–571.PubMedCrossRefGoogle Scholar
  82. 82.
    Sargent D, Sobrero A, Grothey A, et al. Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2009;27(6):872–877.PubMedCrossRefGoogle Scholar
  83. 83.
    Chao M, Gibbs P. Caution is required before recommending routine carcinoembryonic antigen and imaging follow-up for patients with early-stage colon cancer. J Clin Oncol. 2009;27(36):e279-e280. author reply e81.PubMedCrossRefGoogle Scholar
  84. 84.
    Quah HM, Chou JF, Gonen M, et al. Identification of patients with high-risk stage II colon cancer for adjuvant therapy. Dis Colon Rectum. 2008;51(5):503–507.PubMedCrossRefGoogle Scholar
  85. 85.
    Chau I, Allen MJ, Cunningham D, et al. The value of routine serum carcino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer. J Clin Oncol. 2004;22(8):1420–1429.PubMedCrossRefGoogle Scholar
  86. 86.
    NCCN Colon Cancer Panel. Colon Cancer. 2010 [updated 9/10/2010; cited 2010 9/30/2010]; Available from: Scholar
  87. 87.
    Lin JK, Lin CC, Yang SH, et al. Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer. Int J Colorectal Dis. 2011;26:1135–1141.PubMedCrossRefGoogle Scholar
  88. 88.
    Lee WS, Baek JH, Kim KK, Park YH. The prognostic significant of percentage drop in serum CEA post curative resection for colon cancer. Surg Oncol. 2012;21:45–51.PubMedCrossRefGoogle Scholar
  89. 89.
    Cooper GS, Kou TD, Reynolds HL Jr. Receipt of guideline-recommended follow-up in older colorectal cancer survivors: a population-based analysis. Cancer. 2008;113(8):2029–2037.PubMedCrossRefGoogle Scholar
  90. 90.
    Iwanicki-Caron I, Di Fiore F, Roque I, et al. Usefulness of the serum carcinoembryonic antigen kinetic for chemotherapy monitoring in patients with unresectable metastasis of colorectal cancer. J Clin Oncol. 2008;26(22):3681–3686.PubMedCrossRefGoogle Scholar
  91. 91.
    Ailawadhi S, Sunga A, Rajput A, Yang GY, Smith J, Fakih M. Chemotherapy-induced carcinoembryonic antigen surge in patients with metastatic colorectal cancer. Oncology. 2006;70(1):49–53.PubMedCrossRefGoogle Scholar
  92. 92.
    An X, Ding PR, Xiang XJ, et al. Carcinoembryonic antigen surge in metastatic colorectal cancer patients responding to irinotecan combination chemotherapy. Biomarkers. 2010;15(3):243–248.PubMedCrossRefGoogle Scholar
  93. 93.
    Sorbye H, Dahl O. Carcinoembryonic antigen surge in metastatic colorectal cancer patients responding to oxaliplatin combination chemotherapy: implications for tumor marker monitoring and guidelines. J Clin Oncol. 2003;21(23):4466–4467.PubMedCrossRefGoogle Scholar
  94. 94.
    Strimpakos AS, Cunningham D, Mikropoulos C, Petkar I, Barbachano Y, Chau I. The impact of carcinoembryonic antigen flare in patients with advanced colorectal cancer receiving first-line chemotherapy. Ann Oncol. 2010;21(5):1013–1019.PubMedCrossRefGoogle Scholar
  95. 95.
    Wang WS, Lin JK, Lin TC, et al. Carcinoembryonic antigen in monitoring of response to systemic chemotherapy in patients with metastatic colorectal cancer. Int J Colorectal Dis. 2001;16(2):96–101.PubMedCrossRefGoogle Scholar
  96. 96.
    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.PubMedCrossRefGoogle Scholar
  97. 97.
    Sturgeon CM, Duffy MJ, Hofmann BR, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem. 2010;56(6):e1-e48.PubMedCrossRefGoogle Scholar
  98. 98.
    Horie Y, Miura K, Matsui K, et al. Marked elevation of plasma carcinoembryonic antigen and stomach carcinoma. Cancer. 1996;77(10):1991–1997.PubMedCrossRefGoogle Scholar
  99. 99.
    Zhang YH, Li Y, Chen C, Peng CW. Carcinoembryonic antigen level is related to tumor invasion into the serosa of the stomach: study on 166 cases and suggestion for new therapy. Hepatogastroenterology. 2009;56(96):1750–1754.PubMedGoogle Scholar
  100. 100.
    Ohtsuka T, Nakafusa Y, Sato S, Kitajima Y, Tanaka M, Miyazaki K. Different roles of tumor marker monitoring after curative resections of gastric and colorectal cancers. Dig Dis Sci. 2008;53(6):1537–1543.PubMedCrossRefGoogle Scholar
  101. 101.
    Qiu MZ, Lin JZ, Wang ZQ, et al. Cutoff value of carcinoembryonic antigen and carbohydrate antigen 19–9 elevation levels for monitoring recurrence in patients with resectable gastric adenocarcinoma. Int J Biol Markers. 2009;24(4):258–264.PubMedGoogle Scholar
  102. 102.
    Kim HJ, Lee KW, Kim YJ, et al. Chemotherapy-induced transient CEA and CA19–9 surges in patients with metastatic or recurrent gastric cancer. Acta Oncol. 2009;48(3):385–390.PubMedCrossRefGoogle Scholar
  103. 103.
    Sakamoto J, Nakazato H, Teramukai S, et al. Association between preoperative plasma CEA levels and the prognosis of gastric cancer following curative resection. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan. Surg Oncol. 1996;5(3):133–139.PubMedCrossRefGoogle Scholar
  104. 104.
    Ishigami S, Natsugoe S, Hokita S, et al. Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19–9 levels in gastric cancer. J Clin Gastroenterol. 2001;32(1):41–44.PubMedCrossRefGoogle Scholar
  105. 105.
    Kim DY, Kim HR, Shim JH, Park CS, Kim SK, Kim YJ. Significance of serum and tissue carcinoembryonic antigen for the prognosis of gastric carcinoma patients. J Surg Oncol. 2000;74(3):185–192.PubMedCrossRefGoogle Scholar
  106. 106.
    Jung M, Jeung HC, Lee SS, et al. The clinical significance of ascitic fluid CEA in advanced gastric cancer with ascites. J Cancer Res Clin Oncol. 2010;136(4):517–526.PubMedCrossRefGoogle Scholar
  107. 107.
    Yamamoto M, Baba H, Toh Y, Okamura T, Maehara Y. Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients. J Cancer Res Clin Oncol. 2007;133(7):471–476.PubMedCrossRefGoogle Scholar
  108. 108.
    Dilege E, Mihmanli M, Demir U, et al. Prognostic value of preoperative CEA and CA 19–9 levels in resectable gastric cancer. Hepatogastroenterology. 2010;57(99–100):674–677.PubMedGoogle Scholar
  109. 109.
    Lukaszewicz-Zajac M, Mroczko B, Gryko M, Kedra B, Szmitkowski M. Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19–9) in gastric cancer. Clin Exp Med. 2011;11:89–96.PubMedCrossRefGoogle Scholar
  110. 110.
    Ucar E, Semerci E, Ustun H, Yetim T, Huzmeli C, Gullu M. Prognostic value of preoperative CEA, CA 19–9, CA 72–4, and AFP levels in gastric cancer. Adv Ther. 2008;25(10):1075–1084.PubMedCrossRefGoogle Scholar
  111. 111.
    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):1849–1857.PubMedGoogle Scholar
  112. 112.
    Clark GW, Ireland AP, Hagen JA, Collard JM, Peters JH, DeMeester TR. Carcinoembryonic antigen measurements in the management of esophageal cancer: an indicator of subclinical recurrence. Am J Surg. 1995;170(6):597–600. discussion −1.PubMedCrossRefGoogle Scholar
  113. 113.
    Yi Y, Li B, Sun H, et al. Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma. Tumour Biol. 2010;31(4):333–340.PubMedCrossRefGoogle Scholar
  114. 114.
    Setoyama T, Natsugoe S, Okumura H, et al. Carcinoembryonic antigen messenger RNA expression in blood predicts recurrence in esophageal cancer. Clin Cancer Res. 2006;12(20 Pt 1):5972–5977.PubMedCrossRefGoogle Scholar
  115. 115.
    Cvejic D, Savin S, Golubovic S, Paunovic I, Tatic S, Havelka M. Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression. Histopathology. 2000;37(6):530–535.PubMedCrossRefGoogle Scholar
  116. 116.
    Gill S, Cosolo W, Herbertson RA, Berlangieri SU, Scott AM. Medullary carcinoma of the thyroid in a patient with colon cancer and a rising carcinoembryonic antigen level. Intern Med J. 2009;39(4):264–265.PubMedCrossRefGoogle Scholar
  117. 117.
    Angelov A, Klissarova A, Dikranian K. Radioimmunological and immunohistochemical study of carcinoembryonic antigen in pleomorphic adenoma and mucoepidermoid carcinoma of the salivary glands. Gen Diagn Pathol. 1996;141(3–4):229–234.PubMedGoogle Scholar
  118. 118.
    Ohtsuka T, Sato S, Kitajima Y, Tanaka M, Nakafusa Y, Miyazaki K. False-positive findings for tumor markers after curative gastrectomy for gastric cancer. Dig Dis Sci. 2008;53(1):73–79.PubMedCrossRefGoogle Scholar
  119. 119.
    Gallagher DJ, Libby DM, Kemeny N. Elevated carcinoembryonic antigen and sarcoidosis masquerading as metastatic colon cancer. Clin Colorectal Cancer. 2009;8(3):172–174.PubMedCrossRefGoogle Scholar
  120. 120.
    Yanagitani N, Shimizu Y, Kazama T, Dobashi K, Ishizuka T, Mori M. Eosinophilic bronchiolitis indicating eosinophilic airway disease with overexpression of carcinoembryonic antigen in sinus and bronchiole: case report. J Biol Regul Homeost Agents. 2010;24(1):99–102.PubMedGoogle Scholar
  121. 121.
    Kawaguchi G, Abe E, Sasamoto R, Sasai K. Elevation of serum carcinoembryonic antigen level in a patient with hypothyroidism after radiation therapy for cervical esophageal cancer. Int J Clin Oncol. 2010;15(1):104–108.PubMedCrossRefGoogle Scholar
  122. 122.
    Hsu TC. Unusual elevation of CEA in a patient with history of colon cancer. Jpn J Clin Oncol. 2006;36(12):811–813.PubMedCrossRefGoogle Scholar
  123. 123.
    Alexander JC, Silverman NA, Chretien PB. Effect of age and cigarette smoking on carcinoembryonic antigen levels. JAMA. 1976;235(18):1975–1979.PubMedCrossRefGoogle Scholar
  124. 124.
    Fuchs C, Krapf F, Kern P, Hoferichter S, Jager W, Kalden JR. CEA-containing immune complexes in sera of patients with colorectal and breast cancer–analysis of complexed immunoglobulin classes. Cancer Immunol Immunother. 1988;26(2):180–184.PubMedCrossRefGoogle Scholar
  125. 125.
    Koprowski H, Herlyn M, Steplewski Z, Sears HF. Specific antigen in serum of patients with colon carcinoma. Science. 1981;212(4490):53–55.PubMedCrossRefGoogle Scholar
  126. 126.
    Locker GY, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–5327.PubMedCrossRefGoogle Scholar
  127. 127.
    Ventrucci M, Pozzato P, Cipolla A, Uomo G. Persistent elevation of serum CA 19–9 with no evidence of malignant disease. Dig Liver Dis. 2009;41(5):357–363.PubMedCrossRefGoogle Scholar
  128. 128.
    Basbug M, Arikanoglu Z, Bulbuller N, et al. Prognostic value of preoperative CEA and CA 19–9 levels in patients with colorectal cancer. Hepatogastroenterology. 2011;58(106):400–405.PubMedGoogle Scholar
  129. 129.
    Yang XQ, Chen C, Peng CW, Liu SP, Li Y. Carbohydrate antigen 242 highly consists with carbohydrate antigen 19–9 in diagnosis and prognosis of colorectal cancer: study on 185 cases. Med Oncol. 2012;29:1030–1036.PubMedCrossRefGoogle Scholar
  130. 130.
    Kawamura YJ, Tokumitsu A, Mizokami K, Sasaki J, Tsujinaka S, Konishi F. First alert for recurrence during follow-up after potentially curative resection for colorectal carcinoma: CA 19–9 should be included in surveillance programs. Clin Colorectal Cancer. 2010;9(1):48–51.PubMedCrossRefGoogle Scholar
  131. 131.
    Sasaki A, Kawano K, Inomata M, Shibata K, Matsumoto T, Kitano S. Value of serum carbohydrate antigen 19–9 for predicting extrahepatic metastasis in patients with liver metastasis from colorectal carcinoma. Hepatogastroenterology. 2005;52(66):1814–1819.PubMedGoogle Scholar
  132. 132.
    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):142–145.PubMedCrossRefGoogle Scholar
  133. 133.
    Hwang GI, Yoo CH, Sohn BH, et al. Predictive value of preoperative serum CEA, CA19–9 and CA125 levels for peritoneal metastasis in patients with gastric carcinoma. Cancer Res Treat. 2004;36(3):178–181.PubMedCrossRefGoogle Scholar
  134. 134.
    Choi SR, Jang JS, Lee JH, et al. Role of serum tumor markers in monitoring for recurrence of gastric cancer following radical gastrectomy. Dig Dis Sci. 2006;51(11):2081–2086.PubMedCrossRefGoogle Scholar
  135. 135.
    Nakagoe T, Sawai T, Tsuji T, et al. Predictive factors for preoperative serum levels of sialy Lewis(x), sialyl Lewis(a) and sialyl Tn antigens in gastric cancer patients. Anticancer Res. 2002;22(1A):451–458.PubMedGoogle Scholar
  136. 136.
    Sheer DG, Schlom J, Cooper HL. Purification and composition of the human tumor-associated glycoprotein (TAG-72) defined by monoclonal antibodies CC49 and B72.3. Cancer Res. 1988;48(23):6811–6818.PubMedGoogle Scholar
  137. 137.
    Lopez JB, Royan GP, Lakhwani MN, Mahadaven M, Timor J. CA 72–4 compared with CEA and CA 19–9 as a marker of some gastrointestinal malignancies. Int J Biol Markers. 1999;14(3):172–177.PubMedGoogle Scholar
  138. 138.
    Guadagni F, Roselli M, Cosimelli M, et al. CA 72–4 serum marker–a new tool in the management of carcinoma patients. Cancer Invest. 1995;13(2):227–238.PubMedCrossRefGoogle Scholar
  139. 139.
    Carpelan-Holmstrom M, Louhimo J, Stenman UH, Alfthan H, Jarvinen H, Haglund C. Estimating the probability of cancer with several tumor markers in patients with colorectal disease. Oncology. 2004;66(4):296–302.PubMedCrossRefGoogle Scholar
  140. 140.
    Carpelan-Holmstrom M, Louhimo J, Stenman UH, Alfthan H, Jarvinen H, Haglund C. CEA, CA 242, CA 19–9, CA 72–4 and hCGbeta in the diagnosis of recurrent colorectal cancer. Tumour Biol. 2004;25(5–6):228–234.PubMedCrossRefGoogle Scholar
  141. 141.
    Sheng SL, Wang Q, Huang G. Development of time-resolved immunofluorometric assays for CA 72–4 and application in sera of patients with gastric tumors. Clin Chim Acta. 2007;380(1–2):106–111.PubMedCrossRefGoogle Scholar
  142. 142.
    Mattar R. Alves de Andrade CR, DiFavero GM, Gama-Rodrigues JJ, Laudanna AA. Preoperative serum levels of CA 72–4, CEA, CA 19–9, and alpha-fetoprotein in patients with gastric cancer. Rev Hosp Clin Fac Med Sao Paulo. 2002;57(3):89–92.PubMedCrossRefGoogle Scholar
  143. 143.
    Marrelli D, Pinto E, De Stefano A, Farnetani M, Garosi L, Roviello F. Clinical utility of CEA, CA 19–9, and CA 72–4 in the follow-up of patients with resectable gastric cancer. Am J Surg. 2001;181(1):16–19.PubMedCrossRefGoogle Scholar
  144. 144.
    Zou P, Povoski SP, Hall NC, et al. 124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results. World J Surg Oncol. 2010;8:65.PubMedCrossRefGoogle Scholar
  145. 145.
    Fujimura T, Kinami S, Ninomiya I, et al. Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer. Endoscopy. 2002;34(7):569–574.PubMedCrossRefGoogle Scholar
  146. 146.
    Hall NR, Finan PJ, Stephenson BM, Purves DA, Cooper EH. The role of CA-242 and CEA in surveillance following curative resection for colorectal cancer. Br J Cancer. 1994;70(3):549–553.PubMedCrossRefGoogle Scholar
  147. 147.
    Ran Y, Hu H, Zhou Z, et al. Profiling tumor-associated autoantibodies for the detection of colon cancer. Clin Cancer Res. 2008;14(9):2696–2700.PubMedCrossRefGoogle Scholar
  148. 148.
    Small-Howard AL, Harris H. Advantages of the AMDL-ELISA DR-70 (FDP) assay over carcinoembryonic antigen (CEA) for monitoring colorectal cancer patients. J Immunoassay Immunochem. 2010;31(2):131–147.PubMedCrossRefGoogle Scholar
  149. 149.
    Shimada H, Nabeya Y, Okazumi S, et al. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133(5):486–494.PubMedCrossRefGoogle Scholar
  150. 150.
    Ikeda K, Terashima M, Ishida K, et al. Clinical significance of serum levels of SCC antigen in patients with esophageal squamous cell carcinoma. Gan To Kagaku Ryoho. 1988;15(4 Pt 1):677–682.PubMedGoogle Scholar
  151. 151.
    Wild N, Andres H, Rollinger W, et al. A combination of serum markers for the early detection of colorectal cancer. Clin Cancer Res. 2010;16(24):6111–6121.PubMedCrossRefGoogle Scholar
  152. 152.
    Chen C, Chen LQ, Chen LD, Yang GL, Li Y. Evaluation of tumor markers biochip C12 system in the diagnosis of gastric cancer and the strategies for improvement: analysis of 100 cases. Hepatogastroenterology. 2008;55(84):991–997.PubMedGoogle Scholar
  153. 153.
    Ward DG, Suggett N, Cheng Y, et al. Identification of serum biomarkers for colon cancer by proteomic analysis. Br J Cancer. 2006;94(12):1898–1905.PubMedCrossRefGoogle Scholar
  154. 154.
    Qiu FM, Yu JK, Chen YD, Jin QF, Sui MH, Huang J. Mining novel biomarkers for prognosis of gastric cancer with serum proteomics. J Exp Clin Cancer Res. 2009;28:126.PubMedCrossRefGoogle Scholar
  155. 155.
    Lim JY, Cho JY, Paik YH, Chang YS, Kim HG. Diagnostic application of serum proteomic patterns in gastric cancer patients by ProteinChip surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Int J Biol Markers. 2007;22(4):281–286.PubMedGoogle Scholar
  156. 156.
    Ma Y, Peng J, Liu W, et al. Proteomics identification of desmin as a potential oncofetal diagnostic and prognostic biomarker in colorectal cancer. Mol Cell Proteomics. 2009;8(8):1878–1890.PubMedCrossRefGoogle Scholar
  157. 157.
    Chen JS, Chen KT, Fan CW, et al. Comparison of membrane fraction proteomic profiles of normal and cancerous human colorectal tissues with gel-assisted digestion and iTRAQ labeling mass spectrometry. FEBS J. 2010;277(14):3028–3038.PubMedCrossRefGoogle Scholar
  158. 158.
    Liu W, Wang P, Li Z, et al. Evaluation of tumour-associated antigen (TAA) miniarray in immunodiagnosis of colon cancer. Scand J Immunol. 2009;69(1):57–63.PubMedCrossRefGoogle Scholar
  159. 159.
    Tsunemi S, Nakanishi T, Fujita Y, et al. Proteomics-based identification of a tumor-associated antigen and its corresponding autoantibody in gastric cancer. Oncol Rep. 2010;23(4):949–956.PubMedGoogle Scholar
  160. 160.
    Kijanka G, Hector S, Kay EW, et al. Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer. Gut. 2010;59(1):69–78.PubMedCrossRefGoogle Scholar
  161. 161.
    American Society of Clinical Oncology. Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol. 1996;14(10):2843–2877.Google Scholar
  162. 162.
    Bast RC Jr, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19(6):1865–1878.PubMedGoogle Scholar
  163. 163.
    Desch CE, Benson AB 3rd, Somerfield MR, et al. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2005;23(33):8512–8519.PubMedCrossRefGoogle Scholar
  164. 164.
    Guillem JG, Wood WC, Moley JF, et al. ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol. 2006;24(28):4642–4660.PubMedCrossRefGoogle Scholar
  165. 165.
    Klapdor R, Aronsson A, Duffy M, Hansson L, Khalifa R, Lamerz R. Tumour markers in gastrointestinal cancers–EGTM recommendations. European Group on Tumour Markers. Anticancer Res. 1999;19(4A):2811–2815.Google Scholar
  166. 166.
    Duffy MJ, van Dalen A, Haglund C, et al. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer. 2003;39(6):718–727.PubMedCrossRefGoogle Scholar
  167. 167.
    Duffy MJ, van Dalen A, Haglund C, et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer. 2007;43(9):1348–1360.PubMedCrossRefGoogle Scholar
  168. 168.
    Van Cutsem EJ. Advanced colorectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2007;18(Suppl 2):ii25-ii26.PubMedGoogle Scholar
  169. 169.
    Van Cutsem E, Oliveira J. Advanced colorectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Suppl 4):61–63.PubMedGoogle Scholar
  170. 170.
    Van Cutsem E, Nordlinger B, Cervantes A. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Ann Oncol. 2010;21(Suppl 5):v93-v97.PubMedCrossRefGoogle Scholar
  171. 171.
    Balmana J, Castells A, Cervantes A. Familial colorectal cancer risk: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;21(Suppl 5):v78-v81.PubMedCrossRefGoogle Scholar
  172. 172.
    Van Cutsem E, Dicato M, Arber N, et al. Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2009. Ann Oncol. 2010;21(Suppl 6):vi1-vi10.PubMedCrossRefGoogle Scholar
  173. 173.
    Fleisher M, Dnistrian A, Sturgeon C, Lamerz R, Witliff J. Practice guidelines and recommendations for use of tumor markers in the clinic. Tumor Markers: physiology, pathobiology, technology and clinical applications. Washington, DC: AACC Press; 2002:33–63.Google Scholar
  174. 174.
    Chan DW, Booth RA, Diamandis E. Tumor markers. In: Burtis C, Ashwood E, Bruns D, eds. Tietz textbook of clinical chemistry and molecular diagnostics. St. Louis, MI: Elsevier; 2006.Google Scholar
  175. 175.
    Tsai WS, Changchien CR, Yeh CY, et al. Preoperative plasma vascular endothelial growth factor but not nitrite is a useful complementary tumor marker in patients with colorectal cancer. Dis Colon Rectum. 2006;49(6):883–894.PubMedCrossRefGoogle Scholar
  176. 176.
    Babel I, Barderas R, Diaz-Uriarte R, Martinez-Torrecuadrada JL, Sanchez-Carbayo M, Casal JI. Identification of tumor-associated autoantigens for the diagnosis of colorectal cancer in serum using high density protein microarrays. Mol Cell Proteomics. 2009;8(10):2382–2395.PubMedCrossRefGoogle Scholar
  177. 177.
    Holten-Andersen MN, Christensen IJ, Nielsen HJ, et al. Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer. Clin Cancer Res. 2002;8(1):156–164.PubMedGoogle Scholar
  178. 178.
    Nielsen HJ, Brunner N, Jorgensen LN, et al. Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals. Scand J Gastroenterol. 2011;46:60–90.PubMedCrossRefGoogle Scholar
  179. 179.
    Huber K, Kirchheimer JC, Sedlmayer A, Bell C, Ermler D, Binder BR. Clinical value of determination of urokinase-type plasminogen activator antigen in plasma for detection of colorectal cancer: comparison with circulating tumor-associated antigens CA 19–9 and carcinoembryonic antigen. Cancer Res. 1993;53(8):1788–1793.PubMedGoogle Scholar
  180. 180.
    Cordero OJ, Ayude D, Nogueira M, Rodriguez-Berrocal FJ, de la Cadena MP. Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer. Br J Cancer. 2000;83(9):1139–1146.PubMedCrossRefGoogle Scholar
  181. 181.
    Cordero OJ, Imbernon M, Chiara LD, et al. Potential of soluble CD26 as a serum marker for colorectal cancer detection. World J Clin Oncol. 2011;2(6):245–261.PubMedCrossRefGoogle Scholar
  182. 182.
    Melle C, Ernst G, Schimmel B, et al. Discovery and identification of alpha-defensins as low abundant, tumor-derived serum markers in colorectal cancer. Gastroenterology. 2005;129(1):66–73.PubMedCrossRefGoogle Scholar
  183. 183.
    van den Broek I, Sparidans RW, Engwegen JY, et al. Evaluation of human neutrophil peptide-1, -2 and −3 as serum markers for colorectal cancer. Cancer Biomark. 2010;7(2):109–115.PubMedGoogle Scholar
  184. 184.
    Haug U, Rothenbacher D, Wente MN, Seiler CM, Stegmaier C, Brenner H. Tumour M2-PK as a stool marker for colorectal cancer: comparative analysis in a large sample of unselected older adults vs colorectal cancer patients. Br J Cancer. 2007;96(9):1329–1334.PubMedGoogle Scholar
  185. 185.
    Hathurusinghe HR, Goonetilleke KS, Siriwardena AK. Current status of tumor M2 pyruvate kinase (tumor M2-PK) as a biomarker of gastrointestinal malignancy. Ann Surg Oncol. 2007;14(10):2714–2720.PubMedCrossRefGoogle Scholar
  186. 186.
    Fedarko NS, Jain A, Karadag A, Van Eman MR, Fisher LW. Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res. 2001;7(12):4060–4066.PubMedGoogle Scholar
  187. 187.
    Fernandes LC, Kim SB, Matos D. Cytokeratins and carcinoembryonic antigen in diagnosis, staging and prognosis of colorectal adenocarcinoma. World J Gastroenterol. 2005;11(5):645–648.PubMedGoogle Scholar
  188. 188.
    Kawahara M, Chia D, Terasaki PI, et al. Detection of sialylated LewisX antigen in cancer sera using a sandwich radioimmunoassay. Int J Cancer. 1985;36(4):421–425.PubMedCrossRefGoogle Scholar
  189. 189.
    Pasanen P, Eskelinen M, Kulju A, Penttila I, Janatuinen E, Alhava E. Tumour-associated trypsin inhibitor (TATI) in patients with colorectal cancer: a comparison with CEA, CA 50 and CA 242. Scand J Clin Lab Invest. 1995;55(2):119–124.PubMedCrossRefGoogle Scholar
  190. 190.
    Saito N, Kameoka S. Serum laminin is an independent prognostic factor in colorectal cancer. Int J Colorectal Dis. 2005;20(3):238–244.PubMedCrossRefGoogle Scholar
  191. 191.
    Roessler M, Rollinger W, Palme S, et al. Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer. Clin Cancer Res. 2005;11(18):6550–6557.PubMedCrossRefGoogle Scholar
  192. 192.
    Albanopoulos K, Armakolas A, Konstadoulakis MM, et al. Prognostic significance of circulating antibodies against carcinoembryonic antigen (anti-CEA) in patients with colon cancer. Am J Gastroenterol. 2000;95(4):1056–1061.PubMedCrossRefGoogle Scholar
  193. 193.
    Mroczko B, Szmitkowski M, Okulczyk B, Piotrowski Z. Granulocyte-macrophage-colony stimulating factor in patients with colorectal cancer. Folia Histochem Cytobiol. 2001;39(Suppl 2):110–111.PubMedGoogle Scholar
  194. 194.
    Kerber A, Trojan J, Herrlinger K, Zgouras D, Caspary WF, Braden B. The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study. Aliment Pharmacol Ther. 2004;20(9):983–987.PubMedCrossRefGoogle Scholar
  195. 195.
    Leman ES, Schoen RE, Magheli A, Sokoll LJ, Chan DW, Getzenberg RH. Evaluation of colon cancer-specific antigen 2 as a potential serum marker for colorectal cancer. Clin Cancer Res. 2008;14(5):1349–1354.PubMedCrossRefGoogle Scholar
  196. 196.
    Ferroni P, Roselli M, Martini F, et al. Prognostic value of soluble P-selectin levels in colorectal cancer. Int J Cancer. 2004;111(3):404–408.PubMedCrossRefGoogle Scholar
  197. 197.
    Soroush AR, Zadeh HM, Moemeni M, Shakiba B, Elmi S. Plasma prolactin in patients with colorectal cancer. BMC Cancer. 2004;4:97.PubMedCrossRefGoogle Scholar
  198. 198.
    Nam MJ, Kee MK, Kuick R, Hanash SM. Identification of defensin alpha6 as a potential biomarker in colon adenocarcinoma. J Biol Chem. 2005;280(9):8260–8265.PubMedCrossRefGoogle Scholar
  199. 199.
    Yoneda K, Iida H, Endo H, et al. Identification of Cystatin SN as a novel tumor marker for colorectal cancer. Int J Oncol. 2009;35(1):33–40.PubMedGoogle Scholar
  200. 200.
    Lee H, Rhee H, Kang HJ, et al. Macrophage migration inhibitory factor may be used as an early diagnostic marker in colorectal carcinomas. Am J Clin Pathol. 2008;129(5):772–779.PubMedCrossRefGoogle Scholar
  201. 201.
    Pinczower GD, Gianello RD, Williams RP, Preston BN, Preston H, Linnane AW. Monoclonal antibody 4D3 detects small intestinal mucin antigen (SIMA)–glycoprotein in the serum of patients with colorectal cancer. Int J Cancer. 1993;54(3):391–396.PubMedCrossRefGoogle Scholar
  202. 202.
    Eskelinen M, Pasanen P, Janatuinen E, Pettersson N, Linnane A, Alhava E. Small intestinal mucin antigen (SIMA); a novel tumour marker in colorectal cancer? Anticancer Res. 1995;15(5B):2351–2356.PubMedGoogle Scholar
  203. 203.
    Mroczko B, Szmitkowski M, Wereszczynska-Siemiatkowska U, Okulczyk B. Stem cell factor (SCF) and interleukin 3 (IL-3) in the sera of patients with colorectal cancer. Dig Dis Sci. 2005;50(6):1019–1024.PubMedCrossRefGoogle Scholar
  204. 204.
    Kuru B, Ozaslan C, Yalman K, Camlybel M. Serum progesterone levels in patients with gastric and colorectal cancers. Acta Chir Belg. 2002;102(2):122–125.PubMedGoogle Scholar
  205. 205.
    Tagi T, Matsui T, Kikuchi S, et al. Dermokine as a novel biomarker for early-stage colorectal cancer. J Gastroenterol. 2010;45:1201–1211.PubMedCrossRefGoogle Scholar
  206. 206.
    Xia Q, Kong XT, Zhang GA, Hou XJ, Qiang H, Zhong RQ. Proteomics-based identification of DEAD-box protein 48 as a novel autoantigen, a prospective serum marker for pancreatic cancer. Biochem Biophys Res Commun. 2005;330(2):526–532.PubMedCrossRefGoogle Scholar
  207. 207.
    Reipert BM, Tanneberger S, Pannetta A, et al. Increase in autoantibodies against Fas (CD95) during carcinogenesis in the human colon: a hope for the immunoprevention of cancer? Cancer Immunol Immunother. 2005;54(10):1038–1042.PubMedCrossRefGoogle Scholar
  208. 208.
    Yamaguchi A, Kurosaka Y, Ishida T, et al. Clinical significance of tumor marker NCC-ST 439 in large bowel cancers. Dis Colon Rectum. 1991;34(10):921–924.PubMedCrossRefGoogle Scholar
  209. 209.
    Kornek G, Depisch D, Temsch EM, Scheithauer W. Comparative analysis of cancer-associated antigen CA-195, CA 19–9 and carcinoembryonic antigen in diagnosis, follow-up and monitoring of response to chemotherapy in patients with gastrointestinal cancer. J Cancer Res Clin Oncol. 1991;117(5):493–496.PubMedCrossRefGoogle Scholar
  210. 210.
    Yedema KA, Kenemans P, Wobbes T, et al. Carcinoma-associated mucin serum markers CA M26 and CA M29: efficacy in detecting and monitoring patients with cancer of the breast, colon, ovary, endometrium and cervix. Int J Cancer. 1991;47(2):170–179.PubMedCrossRefGoogle Scholar
  211. 211.
    Goodgame R, Kiefe C, Rose E, Sutton F, Brown J, Alpert E. Clinical evaluation of M43: a novel cancer-associated mucin epitope. Cancer Res. 1993;53(12):2803–2809.PubMedGoogle Scholar
  212. 212.
    van Kamp GJ, von Mensdorff-Pouilly S, Kenemans P, et al. Evaluation of colorectal cancer-associated mucin CA M43 assay in serum. Clin Chem. 1993;39(6):1029–1032.PubMedGoogle Scholar
  213. 213.
    Kozwich DL, Kramer LC, Mielicki WP, Fotopoulos SS, Gordon SG. Application of cancer procoagulant as an early detection tumor marker. Cancer. 1994;74(4):1367–1376.PubMedCrossRefGoogle Scholar
  214. 214.
    Herlyn M, Blaszczyk M, Bennicelli J, et al. Selection of monoclonal antibodies detecting serodiagnostic human tumor markers. J Immunol Methods. 1985;80(1):107–116.PubMedCrossRefGoogle Scholar
  215. 215.
    Duraker N, Can D, Parilti M. Measurement of serum total and free prostate-specific antigen in women with colorectal carcinoma. Br J Cancer. 2002;86(2):203–206.PubMedCrossRefGoogle Scholar
  216. 216.
    Severini G. Glutathione S-transferase activity in patients with cancer of the digestive tract. J Cancer Res Clin Oncol. 1993;120(1–2):112–114.PubMedCrossRefGoogle Scholar
  217. 217.
    Kuroki M, Matsushita H, Matsumoto H, Hirose Y, Senba T, Yamamoto T. Nonspecific cross-reacting antigen-50/90 (NCA-50/90) as a new tumor marker. Anticancer Res. 1999;19(6C):5599–5606.PubMedGoogle Scholar
  218. 218.
    Arai M, Sakamoto K, Otsuka H, Yokoyama Y, Akagi M. Detection of tumor associated antigen, PA8–15, in sera from pancreatic and gastrointestinal carcinoma patients. Jpn J Clin Oncol. 1990;20(2):145–153.PubMedGoogle Scholar
  219. 219.
    Riedl S, Bodenmuller H, Hinz U, et al. Significance of tenascin serum level as tumor marker in primary colorectal carcinoma. Int J Cancer. 1995;64(1):65–69.PubMedCrossRefGoogle Scholar
  220. 220.
    Dudouet B, Jacob L, Beuzeboc P, et al. Presence of villin, a tissue-specific cytoskeletal protein, in sera of patients and an initial clinical evaluation of its value for the diagnosis and follow-up of colorectal cancers. Cancer Res. 1990;50(2):438–443.PubMedGoogle Scholar
  221. 221.
    Ayude D, Fernandez-Rodriguez J, Rodriguez-Berrocal FJ, et al. Value of the serum alpha-L-fucosidase activity in the diagnosis of colorectal cancer. Oncology. 2000;59(4):310–316.PubMedCrossRefGoogle Scholar
  222. 222.
    Schneider J, Bitterlich N, Schulze G. Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK. Anticancer Res. 2005;25(3A):1507–1515.PubMedGoogle Scholar
  223. 223.
    Mroczko B, Kozlowski M, Groblewska M, et al. The diagnostic value of the measurement of matrix metalloproteinase 9 (MMP-9), squamous cell cancer antigen (SCC) and carcinoembryonic antigen (CEA) in the sera of esophageal cancer patients. Clin Chim Acta. 2008;389(1–2):61–66.PubMedCrossRefGoogle Scholar
  224. 224.
    Kozlowski M, Kowalczuk O, Milewski R, Chyczewski L, Niklinski J, Laudanski J. Serum vascular endothelial growth factors C and D in patients with oesophageal cancer. Eur J Cardiothorac Surg. 2010;38(3):260–267.PubMedCrossRefGoogle Scholar
  225. 225.
    Dong J, Zeng BH, Xu LH, et al. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma. J Transl Med. 2010;8:81.PubMedCrossRefGoogle Scholar
  226. 226.
    Wu CY, Wu MS, Chiang EP, et al. Plasma matrix metalloproteinase-9 level is better than serum matrix metalloproteinase-9 level to predict gastric cancer evolution. Clin Cancer Res. 2007;13(7):2054–2060.PubMedCrossRefGoogle Scholar
  227. 227.
    Mroczko B, Groblewska M, Lukaszewicz-Zajac M, Bandurski R, Kedra B, Szmitkowski M. Pre-treatment serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in gastric cancer patients. Clin Chem Lab Med. 2009;47(9):1133–1139.PubMedCrossRefGoogle Scholar
  228. 228.
    Wang CS, Wu TL, Tsao KC, Sun CF. Serum TIMP-1 in gastric cancer patients: a potential prognostic biomarker. Ann Clin Lab Sci. 2006;36(1):23–30.PubMedGoogle Scholar
  229. 229.
    Jin B, Wang X, Jin Y, et al. Detection of serum gastric cancer-associated MG7-Ag from gastric cancer patients using a sensitive and convenient ELISA method. Cancer Invest. 2009;27(2):227–233.PubMedCrossRefGoogle Scholar
  230. 230.
    Xia HH, Yang Y, Chu KM, et al. Serum macrophage migration-inhibitory factor as a diagnostic and prognostic biomarker for gastric cancer. Cancer. 2009;115(23):5441–5449.PubMedCrossRefGoogle Scholar
  231. 231.
    Kumar Y, Tapuria N, Kirmani N, Davidson BR. Tumour M2-pyruvate kinase: a gastrointestinal cancer marker. Eur J Gastroenterol Hepatol. 2007;19(3):265–276.PubMedCrossRefGoogle Scholar
  232. 232.
    Thong-Ngam D, Tangkijvanich P, Lerknimitr R, Mahachai V, Theamboonlers A, Poovorawan Y. Diagnostic role of serum interleukin-18 in gastric cancer patients. World J Gastroenterol. 2006;12(28):4473–4477.PubMedGoogle Scholar
  233. 233.
    Xu Y, Zhang L, Hu G. Potential application of alternatively glycosylated serum MUC1 and MUC5AC in gastric cancer diagnosis. Biologicals. 2009;37(1):18–25.PubMedCrossRefGoogle Scholar
  234. 234.
    Hao Y, Yu Y, Wang L, et al. IPO-38 is identified as a novel serum biomarker of gastric cancer based on clinical proteomics technology. J Proteome Res. 2008;7(9):3668–3677.PubMedCrossRefGoogle Scholar
  235. 235.
    Chung HW, Kim JW, Lee JH, et al. Comparison of the validity of three biomarkers for gastric cancer screening: carcinoembryonic antigen, pepsinogens, and high sensitive C-reactive protein. J Clin Gastroenterol. 2009;43(1):19–26.PubMedCrossRefGoogle Scholar
  236. 236.
    Chong PK, Lee H, Zhou J, et al. ITIH3 is a potential biomarker for early detection of gastric cancer. J Proteome Res. 2010;9(7):3671–3679.PubMedCrossRefGoogle Scholar
  237. 237.
    Ashizawa T, Okada R, Suzuki Y, et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer. 2005;8(2):124–131.PubMedCrossRefGoogle Scholar
  238. 238.
    Oue N, Sentani K, Noguchi T, et al. Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients. Int J Cancer. 2009;125(10):2383–2392.PubMedCrossRefGoogle Scholar
  239. 239.
    Chan AO, Chu KM, Lam SK, et al. Early prediction of tumor recurrence after curative resection of gastric carcinoma by measuring soluble E-cadherin. Cancer. 2005;104(4):740–746.PubMedCrossRefGoogle Scholar
  240. 240.
    Kammerer R, Zimmermann W. Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families. BMC Biol. 2012;8:12.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pathology & Cell BiologyColumbia UniversityNew YorkUSA

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