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CA 19-9: Biochemical and Clinical Aspects

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Book cover Advances in Cancer Biomarkers

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 867))

Abstract

CA19-9 (carbohydrate antigen 19-9, also called cancer antigen 19-9 or sialylated Lewis a antigen) is the most commonly used and best validated serum tumor marker for pancreatic cancer diagnosis in symptomatic patients and for monitoring therapy in patients with pancreatic adenocarcinoma. Normally synthesized by normal human pancreatic and biliary ductal cells and by gastric, colon, endometrial and salivary epithelia, CA 19-9 is present in small amounts in serum, and can be over expressed in several benign gastrointestinal disorders. Importantly, it exhibits a dramatic increase in its plasmatic levels during neoplastic disease. However, several critical aspects for its clinical use, such as false negative results in subjects with Lewis a-b- genotype and false positive elevation, occasional and transient, in patients with benign diseases, together with its poor positive predictive value (72.3 %), do not make it a good cancer-specific marker and renders it impotent as a screening tool. In the last years a large number of putative biomarkers for pancreatic cancer have been proposed, most of which is lacking of large scale validation. In addition, none of these has showed to possess the requisite sensitivity/specificity to be introduced in clinical use. Therefore, although with important limitations we well-know, CA 19-9 continues being the only pancreatic cancer marker actually in clinical use.

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References

  1. Duffy MG, Sturgeon C, Lamerz R et al (2010) Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol 21:441–447

    Article  CAS  PubMed  Google Scholar 

  2. Koprowski H, Steplewski Z, Mitchell K et al (1979) Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 5:957–971

    Article  CAS  PubMed  Google Scholar 

  3. Koprowski H, Herlyn M, Steplewski Z, Sears HF (1981) Specific antigen in serum of patients with colon carcinoma. Science 212:53–55

    Article  CAS  PubMed  Google Scholar 

  4. Magnani JL, Brockhaus M, Smith DF et al (1981) A monosialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma. Science 212:55–56

    Article  CAS  PubMed  Google Scholar 

  5. Magnani JL, Steplewski Z, Koprowski H, Ginsburg V (1983) Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res 43:5489–5492

    CAS  PubMed  Google Scholar 

  6. Uhlenbruck G, van Meensel-Maene U, Hanisch FG, Dienst C (1984) Unexpected occurrence of the Ca 19-9 tumor marker in normal human seminal plasma. Hoppe Seylers Z Physiol Chem 365:613–617

    Article  CAS  PubMed  Google Scholar 

  7. Goonetilleke KS, Siriwardena AK (2007) Systematic review of carbohydrate antigen (CA 19–9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 33:266–270

    Article  CAS  PubMed  Google Scholar 

  8. Daniels G (1995) Human blood groups. Blackwell Science Ltd., Oxford

    Google Scholar 

  9. Kannagi R (2002) Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes. Curr Opin Struct Biol 12:599–608

    Article  CAS  PubMed  Google Scholar 

  10. Liu FT, Rabinovich GA (2010) Galectins: regulators of acute and chronic inflammation. Ann N Y Acad Sci 1183:158–182

    Article  CAS  PubMed  Google Scholar 

  11. Crocker PR, Paulson JC, Varki A (2007) Siglecs and their roles in the immune system. Nat Rev Immunol 7:255–266

    Article  CAS  PubMed  Google Scholar 

  12. Hakomori S (1983) Tumor-associated glycolipid antigens defined by monoclonal antibodies. Bull Cancer 70:118–126

    CAS  PubMed  Google Scholar 

  13. Hakomori S (1986) Tumor-associated glycolipid antigens, their metabolism and organization. Chem Phys Lipids 42:209–233

    Article  CAS  PubMed  Google Scholar 

  14. Hakomori S, Kannagi R (1983) Glycosphyngolipids as tumor-associated and differentiation markers. J Natl Cancer Inst (Bethesda) 71:231–251

    CAS  Google Scholar 

  15. Itai S, Nishikata J, Yoneda T et al (1991) Tissue distribution of sialyl 2–3 and 2–6 Lewis a antigens and the significance of serum 2-3/2-6 sialyl Lewis a antigen ratio for the differential diagnosis of malignant and benign disorders of the digestive tract. Cancer (Phila) 67:1576–1587

    Article  CAS  Google Scholar 

  16. Miyazaki K, Ohmori K, Izawa M et al (2004) Loss of disialyl Lewis a, the ligand for lymphocyte inhibitory receptor siglec-7, associated with increased sialyl Lewis a expression on human colon cancers. Cancer Res 64:4498–4505

    Article  CAS  PubMed  Google Scholar 

  17. Izawa M, Kumamoto K, Mitsuoka C et al (2000) Expression of sialyl 6-sulfo Lewis x is inversely correlated with conventional sialyl Lewis x expression in human colorectal cancer. Cancer Res 60:1410–1416

    CAS  PubMed  Google Scholar 

  18. Miyazaki K, Sakuma K, Kawamura YI et al (2012) Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors siglec-7 and -9. J Immunol 188:4690–4700

    Article  CAS  PubMed  Google Scholar 

  19. Galli C, Basso D, Plebani M (2013) CA 19-9: handle with care. Clin Chem Lab Med 51:1369–1383

    Article  CAS  PubMed  Google Scholar 

  20. Basso D, Fabris C, Del Favero G et al (1990) How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? Ital J Gastroenterol 22:1–6

    CAS  PubMed  Google Scholar 

  21. Fabris C, Basso D, Piccoli A et al (1991) Role of local and systemic factors in increasing serum glycoprotein markers of pancreatic cancer. J Med 22:145–156

    CAS  PubMed  Google Scholar 

  22. Basso D, Meggiato T, Fabris C et al (1992) Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis. Clin Investig 70:49–54

    Article  CAS  PubMed  Google Scholar 

  23. Rothenberg ML, Abbruzzese JL, Moore M et al (1996) A rationale for expanding the endpoints for clinical trials in advanced pancreatic carcinoma. Cancer 78:627–632

    Article  CAS  PubMed  Google Scholar 

  24. Albert MB, Steinberg WM, Henry JP (1988) Elevated serum levels of tumor marker CA 19-9 in acute cholangitis. Dig Dis Sci 33:1223–1225

    Article  CAS  PubMed  Google Scholar 

  25. Duffy MJ (2007) Role of tumor markers in patients with solid cancers: a critical review. Eur J Intern Med 18:175–184

    Article  CAS  PubMed  Google Scholar 

  26. Steinberg W (1990) The clinical utility of the CA 19-9 tumor associate antigen. Am J Gastroenterol 85:350–355

    CAS  PubMed  Google Scholar 

  27. Kim JE, Lee KT, Lee JK et al (2004) Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol 19:182–186

    Article  PubMed  Google Scholar 

  28. Chang CY, Huang SP, Chiu HM et al (2006) Low efficacy of serum levels of CA 19-9 in prediction of malignant diseases in asymptomatic population in Taiwan. Hepatogastroenterology 53:1–4

    PubMed  Google Scholar 

  29. Kim HR, Lee CH, Kim YW et al (2009) Increased CA 19-9 level in patients without malignant disease. Clin Chem Lab Med 47:750–754

    Article  CAS  PubMed  Google Scholar 

  30. Kim YC, Kim HJ, Park JH et al (2009) Can preoperative CA19-9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma? J Gastroenterol Hepatol 24:1869–1875

    Article  CAS  PubMed  Google Scholar 

  31. Ventrucci M, Pozzato P, Cipolla A, Uomo G (2009) Persistent elevation of serum CA 19-9 with no evidence of malignant disease. Dig Liver Dis 41:357–363

    Article  CAS  PubMed  Google Scholar 

  32. Sakahara H, Endo K, Nakajima K et al (1986) Serum CA 19-9 concentrations and computed tomography findings in patients with pancreatic carcinoma. Cancer 57:1324–1326

    Article  CAS  PubMed  Google Scholar 

  33. Frebourg T, Bercoff E, Manchon N et al (1988) The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. A prospective study of 866 patients. Cancer 62:2287–2290

    Article  CAS  PubMed  Google Scholar 

  34. Fabris C, Del Favero G, Basso D et al (1988) Serum markers and clinical data in diagnosing pancreatic cancer: a contrastive approach. Am J Gastroenterol 83:549–553

    CAS  PubMed  Google Scholar 

  35. National Health Insurance Corporation (2000) National health insurance statistical yearbook 1999, 21:350–563

    Google Scholar 

  36. La’ulu SL, Roberts WL (2007) Performance characteristics of five automated CA 19-9 assays. Am J Clin Pathol 127:436–440

    Article  PubMed  Google Scholar 

  37. Hotakainen K, Tanner P, Alfthan H et al (2009) Comparison of three immunoassays for CA 19–9. Clin Chim Acta 400:123–127

    Article  CAS  PubMed  Google Scholar 

  38. Deinzer M, Faissner R, Metzger T et al (2010) Comparison of two different methods for CA19-9 antigen determination. Clin Lab 56:319–325

    CAS  PubMed  Google Scholar 

  39. Passerini R, Cassatella MC, Boveri S et al (2012) The pitfalls of CA 19–9: routine testing and comparison of two automated immunoassays in a reference oncology center. Am J Clin Pathol 138:281–287

    Article  CAS  PubMed  Google Scholar 

  40. Sturgeon C, Dati F, Duffy MJ et al (1999) Quality requirements and control: EGTM recommendations. Anticancer Res 19:2785–2820

    Google Scholar 

  41. Biguet B, Habersetzer F, Beaudonnet A et al (1995) Discordant CA 19.9 serum results by microparticle enzyme immunoassay and immunoradiometric assay. Clin Chem 41:1057–1058

    CAS  PubMed  Google Scholar 

  42. Berth M, Bosmans E, Everaert J et al (2006) Rheumatoid factor interference in the determination of carbohydrate antigen 19-9 (CA 19-9). Clin Chem Lab Med 44:1137–1139

    Article  CAS  PubMed  Google Scholar 

  43. Liang Y, Yang Z, Ye W et al (2009) Falsely elevated carbohydrate antigen 19-9 level due to heterophilic antibody interference but not rheumatoid factor: a case report. Clin Chem Lab Med 47:116–117

    Article  CAS  PubMed  Google Scholar 

  44. Troup S (2012) Analyte monographs alongside the National Laboratory Medicine Catalogue. The Association for Clinical Biochemistry and Laboratory Medicine, London

    Google Scholar 

  45. Gillen S, Schuster T, Meyer zum Büschenfelde C et al (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7, e1000267

    Article  PubMed Central  PubMed  Google Scholar 

  46. Brentnall TA, Bronner MP, Byrd DR et al (1999) Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 131:247–255

    Article  CAS  PubMed  Google Scholar 

  47. Canto MIGM, Yeo CJ, Griffin C, Axilbund JE et al (2003) Screening for pancreatic neoplasia in high risk individuals. Clin Gastroenterol Hepatol 2:606–621

    Article  Google Scholar 

  48. Canto MI, Hruban RH, Fishman EK et al (2012) Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology 142:796

    Article  PubMed Central  PubMed  Google Scholar 

  49. Canto MI, Harinck F, Hruban RH et al (2013) International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familiar pancreatic cancer. Gut 62:339

    Article  PubMed Central  PubMed  Google Scholar 

  50. Konstantinou F, Syrigos KN, Saif MW (2013) Pancreatic cancer: what about screening and detection? Highlights from the “2013 ASCO Annual Meeting”, Chicago, 30 May–4 June 2013

    Google Scholar 

  51. Berger AC, Meszoely IM, Ross EA et al (2004) Undetectable preoperative levels of serum CA 19-9 correlate with improved survival for patients with resectable pancreatic adenocarcinoma. Ann Surg Oncol 11:644–649

    Article  PubMed  Google Scholar 

  52. Smith RA, Bosonnet L, Ghaneh P et al (2008) Preoperative CA19-9 levels and lymph node ratio are independent predictors of survival in patients with resected pancreatic ductal adenocarcinoma. Dig Surg 25:226–232

    Article  CAS  PubMed  Google Scholar 

  53. Zhang S, Wang YM, Sun CD et al (2008) Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma. World J Gastroenterol 14:3750–3753

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Waraya M, Yamashita K, Katagiri H et al (2009) Preoperative serum CA19-9 and dissected peripancreatic tissue margin as determiners of long-term survival in pancreatic cancer. Ann Surg Oncol 16:1231–1240

    Article  PubMed  Google Scholar 

  55. Ferrone CR, Finkelstein DM, Thayer SP et al (2006) Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol 24:2897–2902

    Article  CAS  PubMed  Google Scholar 

  56. Kondo N, Murakami Y, Uemura K et al (2010) Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol 17:2321–2329

    Article  PubMed  Google Scholar 

  57. Schlieman MG, Ho HS, Bold RJ et al (2003) Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg 138:951–955

    Article  PubMed  Google Scholar 

  58. Montgomery RC, Hoffman JP, Riley LB et al (1997) Prediction of recurrence and survival by post resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol 4:551–556

    Article  CAS  PubMed  Google Scholar 

  59. Willett CG, Daly WJ, Warshaw AL (1996) CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer. Am J Surg 172:350–352

    Article  CAS  PubMed  Google Scholar 

  60. Halm U, Schumann T, Schiefke I et al (2000) Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer. Br J Cancer 82:1013–1016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Maisey NR, Norman AR, Hill A et al (2005) CA19-9 as a prognostic factor in inoperable pancreatic cancer: the implication for clinical trials. Br J Cancer 93:740–743

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Takahashi H, Ohigashi H, Ishikawa O et al (2010) Serum CA19-9 alterations during preoperative gemcitabine-based chemoradiation therapy for resectable invasive ductal carcinoma of the pancreas as an indicator for therapeutic selection and survival. Ann Surg 251:461–469

    Article  PubMed  Google Scholar 

  63. Bauer TM, El-Rayes BF, Li X et al (2013) Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer 119:285–292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Hernandez JM, Cowgill SM, Al-Saadi S et al (2009) CA 19-9 velocity predicts disease-free survival and overall survival after pancreatectomy of curative intent. J Gastrointest Surg 13:349–353

    Article  PubMed  Google Scholar 

  65. Reni M, Cereda S, Balzano G et al (2009) Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma. Cancer 115:2630–2639

    Article  CAS  PubMed  Google Scholar 

  66. Ballehaninna UK, Chamberlain RS (2012) The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol 3:105–119

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Jancík S, Drábek J, Radzioch D, Hajdúch M (2010) Clinical relevance of KRAS in human cancers. J Biomed Biotechnol 2010:150960

    Article  PubMed Central  PubMed  Google Scholar 

  68. Garcea G, Neal CP, Pattenden CJ et al (2005) Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer 41:2213–2236

    Article  CAS  PubMed  Google Scholar 

  69. Er TK, Chen CC, Bujanda L, Herreros-Villanueva M (2014) Clinical relevance of KRAS mutations in codon 13: where are we? Cancer Lett 343:1–5

    Article  CAS  PubMed  Google Scholar 

  70. Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358:15–16

    Article  CAS  PubMed  Google Scholar 

  71. Talar-Wojnarowska R, Malecka-Panas E (2006) Molecular pathogenesis of pancreatic adenocarcinoma: potential clinical implications. Med Sci Monit 12:RA186–RA193

    CAS  PubMed  Google Scholar 

  72. Wang Y, Gao J, Li Z et al (2007) Diagnostic value of mucins (MUC1, MUC2 and MUC5AC) expression profile in endoscopic ultrasound-guided fine-needle aspiration specimens of the pancreas. Int J Cancer 121:2716–2722

    Article  CAS  PubMed  Google Scholar 

  73. Ringel J, Lohr M (2003) The MUC gene family: their role in diagnosis and early detection of pancreatic cancer. Mol Cancer 2:9

    Article  PubMed Central  PubMed  Google Scholar 

  74. Moniaux N, Andrianifahanana M, Brand RE, Batra SK (2004) Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy. Br J Cancer 91:1633–1638

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Yokoyama S, Kitamoto S, Higashi M et al (2014) Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice. PLoS One 9, e93760

    Article  PubMed Central  PubMed  Google Scholar 

  76. Senapati S, Gnanapragassam VS, Moniaux N (2012) Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells. Oncogene 31:3346–3356

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Lee EJ, Gusev Y, Jiang J et al (2007) Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer 120:1046–1054

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Wang J, Chen J, Chang P et al (2009) MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila) 2:807–813

    Article  CAS  Google Scholar 

  79. Humeau M, Torrisani J, Cordelier P (2013) miRNA in clinical practice: pancreatic cancer. Clin Biochem 46:933–936

    Article  CAS  PubMed  Google Scholar 

  80. Singh S, Chitkara D, Kumar V, Behrman SW, Mahato RI (2013) miRNA profiling in pancreatic cancer and restoration of chemosensitivity. Cancer Lett 334:211–220

    Article  CAS  PubMed  Google Scholar 

  81. Liu J, Gao J, Du Y et al (2012) Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer 131:683–691

    Article  CAS  PubMed  Google Scholar 

  82. Wang WS, Liu LX, Li GP et al (2013) Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer. Cancer Prev Res (Phila) 6:331–338

    Article  CAS  Google Scholar 

  83. Liu R, Chen X, Du Y et al (2012) Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem 58:610–618

    Article  CAS  PubMed  Google Scholar 

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  1. Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo Gemelli 8, 00168, Rome, Italy

    Salvatore Scarà, Patrizia Bottoni & Roberto Scatena

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  1. Salvatore Scarà
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  2. Patrizia Bottoni
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Correspondence to Patrizia Bottoni .

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  1. Institute of Biochemistry and Clinical B, Catholic University School of Medicine, Rome, Italy

    Roberto Scatena

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Scarà, S., Bottoni, P., Scatena, R. (2015). CA 19-9: Biochemical and Clinical Aspects. In: Scatena, R. (eds) Advances in Cancer Biomarkers. Advances in Experimental Medicine and Biology, vol 867. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7215-0_15

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