CA 19-9: Handle with care

Clinical Chemistry and Laboratory Medicine

Volumn 51, Issue 7, 2013, Pages 1369-1383

  Galli, Claudio ^a   Basso, Daniela ^b   Plebani, Mario ^b  

^a ABBOTT DIAGNOSTICS   (Italy)

^b UNIVERSITY HOSPITAL OF PADOVA   (Italy)

Author keywords

CA 19 9; interference; monoclonal antibodies; neoplastic diseases; pancreatic cancer; tumor markers

Indexed keywords

BILIRUBIN; CA 19-9 ANTIGEN; CAPECITABINE; EPIDERMAL GROWTH FACTOR; FERRITIN; GEMCITABINE; HETEROPHILE ANTIBODY; OXALIPLATIN; RHEUMATOID FACTOR;

ACUTE PHASE RESPONSE; BILE DUCT CARCINOMA; BILIRUBIN BLOOD LEVEL; BLOOD GROUP LEWIS SYSTEM; BRONCHIECTASIS; BRONCHIOLITIS; CANCER ADJUVANT THERAPY; CANCER EPIDEMIOLOGY; CANCER PATIENT; CANCER SURGERY; CLINICAL PRACTICE; COHORT ANALYSIS; COLORECTAL CANCER; COMPUTER ASSISTED TOMOGRAPHY; CYTOTOXICITY; DIAGNOSTIC IMAGING; EARLY DIAGNOSIS; EMPHYSEMA; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; ENZYME IMMUNOASSAY; EXTRAHEPATIC BILE DUCT OBSTRUCTION; FALSE POSITIVE RESULT; FIBROSING ALVEOLITIS; FOLLOW UP; GALLBLADDER CARCINOMA; HEPATITIS C; HOMOZYGOSITY; HOSPITAL ADMISSION; HUMAN; INCIDENTAL FINDING; INTERMETHOD COMPARISON; JAUNDICE; LIVER CIRRHOSIS; LIVER FUNCTION; LIVER METASTASIS; NUCLEAR MAGNETIC RESONANCE IMAGING; OBSERVATIONAL STUDY; OVERALL SURVIVAL; PANCREAS CANCER; PANCREATIC NEUROENDOCRINE TUMOR; PATIENT MONITORING; PERIOPERATIVE PERIOD; PHENOTYPE; POSITRON EMISSION TOMOGRAPHY; PREDICTIVE VALUE; PREOPERATIVE PERIOD; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; RADIOIMMUNOASSAY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEIVER OPERATING CHARACTERISTIC; RECURRENCE RISK; REVIEW; SENSITIVITY AND SPECIFICITY; STOMACH ADENOCARCINOMA; SYSTEMIC THERAPY; TREATMENT DURATION; TREATMENT FAILURE; TREATMENT RESPONSE;

ANTIBODIES, MONOCLONAL; CA-19-9 ANTIGEN; FALSE POSITIVE REACTIONS; GASTROINTESTINAL NEOPLASMS; HUMANS; IMMUNOENZYME TECHNIQUES; PANCREATIC NEOPLASMS; RADIOIMMUNOASSAY; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY; TUMOR MARKERS, BIOLOGICAL;

EID: 84882965728     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/cclm-2012-0744     Document Type: Review

References (73)

1. Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 1979;5:957-71. (Pubitemid 10132218)
2. Magnani JL, Steplewski Z, Koprowski H, Ginsburg V. 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 1983;43:5489-92. (Pubitemid 14230170)
3. Goonnetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 2007;33:266-70. (Pubitemid 46488663)
4. Duffy MG, Sturgeon C, Lamerz R, Haglund C, Holubec VL, Klaptor R, et al. Tumor markers in pancreatic cancer: A European Group on Tumor Markers (EGTM) status report. Ann Oncol 2010;21:441-7.
5. Klapdor R, Aronsson AC, Duffy MJ, Nilsson O, Sturpeou C, Topolcau O, et al. Tumor markers in gastrointestinal cancers, EGTM recommendations. Anticancer Res 1999;19:2785-820.
6. Trap è J, Filella X, Alsina-Donadieu M, Juan-Pereira L, Bosch-Ferrers A, Rigo-Bonnin R. Increased plasma concentrations of tumour markers in the absence of neoplasia. Clin Chem Lab Med 2011;49:1605-20.
7. Sturgeon CM, Viljoen A. Analytical error and interference in immunoassay: Minimizing risk. Ann Clin Biochem 2011;48: 418-32.
8. Inoue K, Okada K, Taki Y, Goto R, Kinomura S, Kaneta T, et al. Increase of serum CA 19-9 level without an evident lesion on conventional imaging is insufficient for justification of 18 FDPET examination. Hepatogastroenterology 2008;55:46-9. (Pubitemid 351462160)
9. Basso D, Meggiato T, Fabris C, Plebani M, Fogar P, Panozzo MP, et al. Alterations in bilirubin metabolism during extra-and intrahepatic cholestasis. Clin Investig 1992;70:49-54.
10. Fabris C, Basso D, Piccoli A, Meggiato T, Del Favero G, Fogar P, et al. Role of local and systemic factors in increasing serum glycoprotein markers of pancreatic cancer. J Med 1991;22: 145-56.
11. Basso D, Fabris C, Del Favero G, Piccoli A, Angonese C, Pasquali C, et al. How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? Ital J Gastroenterol 1990;22:1-6. (Pubitemid 20123649)
12. Kim HR, Lee CH, Kim YW, Han SK, Shim YS, Yim JJ. Increased CA 19-9 level in patients without malignant disease Clin Chem Lab Med 2009;47:750-4.
13. Bertino G, Ardiri AM, Boemi P, Bruno CM, Valenti M, Mazzarino MC, et al. Meaning of elevated CA 19-9 serum levels in chronic hepatitis and HCV-related cirrhosis. Minerva Gastroenterol Dietol 2007;53:305-9. (Pubitemid 351169824)
14. Molina V, Visa L, Conill C, Navarro S, Escudero JM, Auge JM, et al. CA 19-9 in pancreatic cancer: Retrospective evaluation of patients with suspicion of pancreatic cancer. Tumor Biol 2012;33:799-807.
15. Berth M, Bosmans E, Everaert J, Dierick J, Schiettekatte J, Anckaert E, et al. Rheumatoid factor interference in the determination of carbohydrate antigen 19-9 (CA 19-9). Clin Chem Lab Med 2006;44:1137-9. (Pubitemid 44370937)
16. Liang Y, Yang Z, Ye W, Yang J, He M, Zhong R. Falsely elevated carbohydrate antigen 19-9 level due to heterophilic antibody interference but not rheumatoid factor: A case report. Clin Chem Lab Med 2009;47:116-7.
17. Passerini R, Cassatella MC, Boveri S, Salvatici M, Radice D, Zorzino L, et al. The pitfalls of CA 19-9: Routine testing and comparison of two automated immunoassays in a reference oncology center. Am J Clin Pathol 2012;138:281-7.
18. Osswald BR, Klee FE, Wysocki S. The reliability of highly elevated CA 19-9 levels. Dis Markers 1993;11:275-8. (Pubitemid 24171604)
19. 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;4:357-63.
20. Kim BJ, Lee KT, Moon TG, Kang P, Lee JK, Kim JJ, et al. How do we interpret an elevated carbohydrated antigen CA 19-9 level in asymptomatic subjects? Dig Liver Dis 2009;41:364-9.
21. Kannagi R. Carbohydrate antigen sialyl Lewis a-its pathophysiological significance and induction mechanism in cancer progression. Chang Gung Med 2007;30:189-209. (Pubitemid 47235445)
22. Partyka K, Maupin KA, Brand RE, Haab BB. Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretation. Proteomics 2012;12:2212-20.
23. .ørntoft TF, Holmes EH, Johnson PH, Hakomori S-I, Clausen H. Differential tissue expression of the Lewis blood group antigens: Enzymatic, immunohistologic, and immunochemical evidence for Lewis a and b antigen expression in Le(a2b2) individuals. Blood 1991;77:1389-96.
24. Hamada E, Taniguchi T, Baba S, Maekawa M. Investigation of unexpected CA 19-9 elevation in Lewis-negative cancer patients. Ann Clin Biochem 2012;49:266-72.
25. Narimatsu H, Iwasaki H, Nakayama F, Ikehara Y, Kudo T, Nishihara S, et al. Lewis and Secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients. Cancer Res 1998;58:512-8. (Pubitemid 28087416)
26. Passerini R, Riggio D, Salvatici M, Zorzino L, Radice D, Sandri MT. Interchangeability of measurements of CA 19-9 in serum with four frequently used assays: An update. Clin Chem Lab Med 2007;45:100-4. (Pubitemid 46155569)
27. Láulu SL, Roberts WL. Performance characteristics of five automated CA 19-9 assays. Am J Clin Pathol 2007;127: 436-40. (Pubitemid 46806338)
28. Hotakainen K, Tanner P, Alfthan H, Haglund K, Stenman U-H. Comparison of three immunoassays for CA 19-9. Clin Chim Acta 2009;400:123-7.
29. Zur B, Holdenrieder S, Albers E, Waldenbach-Bruenagel G, Stoffel-Wagner B. Method comparison for CA 15-3, CA 19-9, and CA 125 determination using the new loci technique of Dimension Vista 1500 and Immulite 2000 XPI. J Immunoassay Immunochem 2012;33:435-45.
30. Plebani M, Giacomini A, Beghi L, De Paoli M, Roveroni G, Galeotti F, et al. Serum tumor markers in monitoring patients: Interpretation of results using analytical and biological variation. Anticancer Res 1996;16:2249-52. (Pubitemid 26265573)
31. Duffy MJ. Role of tumor markers in patients with solid cancers: A critical review. Eur J Intern Med 2007;18:175-84. (Pubitemid 46628757)
32. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30. (Pubitemid 40310185)
33. Tzeng CW, Fleming JB, Lee JE, Wang X, Pisters PW, Vauthey J-N, et al. Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy. HPB (Oxford) 2012,14:365-72.
34. Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006;24:5313-27. (Pubitemid 46631379)
35. Yip D, Karapetis C, Strickland A, Steer CB, Goldstein D. Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer [review]. Cochrane Database Syst Rev 2006;3:CD002093.
36. Halm U, Schumann T, Schiefke I, Witzigmann H, Mössner J, Keim V. Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer. Br J Cancer 2000;82:1013-6. (Pubitemid 30128852)
37. Stemmler J, Stieber P, Szymala AM, Schalhorn A, Schermuly MM, Wilkowski R, et al. Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin? Onkologie 2003;26:462-7. (Pubitemid 37409891)
38. Ko AH, Hwang J, Venook AP, Abbruzzese JL, Bergsland EK, Tempero MA. Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer. Br J Cancer 2005;93:195-9. (Pubitemid 41133205)
39. Hess V, Glimelius B, Grawe P, Dietrich D, Bodoky G, Ruhstaller T, et al. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. Lancet Oncol 2008;9:132-8.
40. Klapdor R, Bahlo M, Babinski A, Klapdor S. CA 19-9 serum concentrations-analysis of the serum kinetics during first-line therapy of pancreatic cancer in relation to overall survival. Anticancer Res 2010;30:1869-74.
41. Tian F, Appert HE, Myles J, Howard JM. Prognostic value of serum CA 19-9 levels in pancreatic adenocarcinoma. Ann Surg 1992;215:350-5.
42. Lundin J, Roberts PJ, Kuusela P, Haglund C. The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients with pancreatic cancer. Br J Cancer 1994;69:515-9. (Pubitemid 24076471)
43. Ishii H, Okada S, Nose H, Yoshimori M, Aoki K, Okusaka T. Prognostic factors in patients with advanced pancreatic cancer treated with systemic chemotherapy. Pancreas 1996;12:267-71. (Pubitemid 26092764)
44. Ziske C, Schlie C, Gorschlueter M, Glasmacher A, Mey U, Strehl J, et al. Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine. Br J Cancer 2003;89:1413-7. (Pubitemid 37386593)
45. Haas M, Laubender RP, Stieber P, Holdenrieder R, Bruns CJ, Wilkowski R, et al. Prognostic relevance of CA 19-9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer. Tumor Biol 2010;31:251-7.
46. Hallemeier CL, Botros M, Corsini MM, Haddock MG, Gunderson LL, Miller RC. Preoperative CA 19-9 level is an important prognostic factor in patients with pancreatic adenocarcinoma treated with surgical resection and adjuvant concurrent chemoradiotherapy. Am J Clin Oncol 2011;34:567-72.
47. Buenger S, Laubert T, Roblick UJ, Habermann JK. Serum biomarkers for improved diagnostic of pancreatic cancer: A current overview. J Cancer Res Clin Oncol 2011;137:375-89.
48. Berger AC, Meszoely IM, Ross EA, Watson JC, Hoffman JP. Undetectable preoperative levels of serum CA 19-9 correlate with improved survival for patients with resectable pancreatic adenocarcinoma. Ann Surg Oncol 2004;11:644-9. (Pubitemid 40486698)
49. Kang CM, Kim JY, Choi GH, Kim KS, Choi JS, Lee WJ, et al. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res 2007;140:31-5. (Pubitemid 46669540)
50. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012;3:105-19.
51. Hata S, Sakamoto Y, Yamamoto Y, Nara S, Esaki M, Shimada K, et al. Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer. Ann Surg Oncol 2012;19: 636-41.
52. Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, et al. for the NSW Pancreatic Cancer Network. The prognostic and predictive value of serum CA 19.9 in pancreatic cancer. Ann Oncol 2012;23:1713-22.
53. Goldstein D, Spry N, Cummins MM, Brown C, van Hazel GA, Carroll S, et al. on behalf of the Australasian Gastro-Intestinal Trials Group. The GOFURTGO Study: AGITG Phase II Study of fixed dose rate gemcitabine-oxaliplatin integrated with concomitant 5FU and 3-D conformal radiotherapy for the treatment of localized pancreatic cancer. Br J Cancer 2012;106:61-9.
54. Rustin GJ, Nelstrop AE, McClean P, Brady MF, McGuire WP, Hoskins WJ, et al. Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125. J Clin Oncol 1996;14:1545-51. (Pubitemid 26134212)
55. Altwegg R, Ychou M, Guillaumon V, Thezenas S, Senesse P, Flori N, et al. Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer. World J Gastroenterol 2012;18:1357-64.
56. Sugiura T, Uesaka K, Kanemoto H, Mizuno T, Sasaki K, Furukawa H, et al. Serum CA 19-9 is significant predictor among preoperative parameters for early recurrence after resection of pancreatic adenocarcinoma. J Gastronintest Surg 2012;16: 977-85.
57. Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom K, 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:e1-48.
58. Kwon OK, Yu W, Chung H. Prognostic value of postoperative CA19-9 normalization in patients with advanced gastric cancer. Hepato-Gastroenterology 2012;60: DOI: 10.5754/hge12585.
59. Takahashi Y, Takeuchi T, Sakamoto J, Touge T, Mai M, Ohkura H, et al. The usefulness of CEA and/or CA 19-9 in monitoring for recurrence in gastric cancer patients: A prospective clinical study. Gastric Cancer 2003;6:142-5. (Pubitemid 37221564)
60. Kim HJ, Lee K-W, Kim YJ, Oh D-Y, Kim JH, Im S-A, et al. Chemotherapy-induced transient CEA and CA 19-9 surges in patients with metastatic or recurrent gastric cancer. Acta Oncol 2009;48:395-0.
61. Qiu MZ, Lin JZ, Wang ZQ, Wang FH, Pan ZZ, Luo HY, 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;24:258-64.
62. Choi SR, Jang JS, Lee JH, Roh MH, Kim MC, Lee WS, et al. Role of serum tumor markers in monitoring for recurrence of gastric cancer following radical gastrectomy. Dig Dis Sci 2006;51:2081-6. (Pubitemid 44832595)
63. Li Y, Yang Y, Lu M, Shen L. Predictive value of serum CEA, CA19-9 and CA72.4 in early diagnosis of recurrence after radical resection of gastric cancer. Hepato-Gastroenterol 2011;58:2166-70.
64. Kim DH, Oh SJ, Oh CA, Choi MG, Noh JH, Sohn TS, et al. The relationships between perioperative CEA, CA 19-9, and CA 72-4 and recurrence in gastric cancer patients after curative radical gastrectomy. J Surg Oncol 2011;104:585-91.
65. Ward U, Primrose JN, Finan PJ, Perren TJ, Selby P, Purves DA, et al. The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer. Br J Cancer 1993;67:1132-5. (Pubitemid 23147517)
66. Yang X-Q, Chen C, Wang F-B, Penc C-W, Li Y. Preoperative serum carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125 as prognostic factors for recurrencefree survival in colorectal cancer. Asian Pacific J Cancer Prev 2011;12:1251-6.
67. Lumachi F. Marino F, Orlando R, Chiara GB, Basso SM. Simultaneous multianalyte immunoassay measurement of five serum tumor markers in the detection of colorectal cancer. Anticancer Res 2012;32:985-8.
68. de Haas RJ, Wichters DA, Flores E, Ducreux M, Lé vi F, Paule B, et al. Tumor marker evolution: Comparison with imaging for assessment of response to chemotherapy in patients with colorectal liver metastases. Ann Surg Oncol 2010;17:1010-23.
69. Holdenrieder S, Stieber P, Liska V, Treska V, Topolcan O, Dreslerova J, et al. Cytokeratin serum biomarkers in patients with colorectal cancer. Anticancer Res 2012;32:1971-6.
70. Petrioli R, Licchetta A, Roviello G, Pascucci A, Francini E, Bargagli G, and the Multidisciplinary Oncology Group on Gastrointestinal Tumors. CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab. Cancer Invest 2012;30:65-71.
71. Lin P-C, Lin J-K, Lin C-C, Wang H-S, Yang S-H, Jiang J-K, et al. Carbohydrate antigen 19-9 is a valuable prognostic factor in colorectal cancer patients with normal levels of carcinoembryonic antigen and may help predict lung metastasis. Int J Colorectal Dis 2012;27:1333-8.
72. Vestergaard EM, Hein HO, Meyer H, Grunnet N, Joergensen J, Wolf H, et al. Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem 1999;45:54-61. (Pubitemid 29036385)
73. Erden G, Barazi AO, Tezcan G, Yildirimkaya MM. Biological variation and reference change values of CA 19-9, CEA, AFP in serum of healthy individuals. Scand J Clin Lab Invest 2008;68:212-8. (Pubitemid 351630827)