Serum and bile markers for cholangiocarcinoma

Seminars in Liver Disease

Volumn 24, Issue 2, 2004, Pages 139-154

  Nehls, Oliver ^a   Gregor, Michael ^a   Klump, Bodo ^a  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

Author keywords

Bile marker; Cholangiocarcinogenesis; Cholangiocarcinoma; Serum marker

Indexed keywords

CA 19-9 ANTIGEN; CYTOKINE; INTERLEUKIN 6; K RAS PROTEIN; LACTIC ACID; PANCREAS POLYPEPTIDE; PEPTIDE; PROTEIN P14ARF; PROTEIN P16; PROTEIN P53; PROTEINASE; TRYPSINOGEN; TUMOR ANTIGEN; TUMOR MARKER;

BILE; BILE DUCT CARCINOMA; BIOCHEMISTRY; CARCINOGENESIS; DIAGNOSTIC ACCURACY; DNA METHYLATION; EARLY DIAGNOSIS; GENE MUTATION; HIGH RISK POPULATION; HUMAN; PRIORITY JOURNAL; REVIEW; SERUM;

ANTIGENS, NEOPLASM; BILE DUCT NEOPLASMS; BILE DUCTS, INTRAHEPATIC; CHOLANGIOCARCINOMA; CYTOKINES; GENETIC MARKERS; HUMANS; TUMOR MARKERS, BIOLOGICAL;

EID: 2942530868     PISSN: 02728087     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-828891     Document Type: Review

References (138)

1. Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001;33:1353-1357.
2. Taylor-Robinson SD, Toledano MB, Arora S, et al. Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales, 1968-1998. Gut 2001;48:816-820
3. Khan SA, Taylor-Robinson SD, Toledano MB, et al. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol 2002;37:806-813
4. Davillla JA, El-Serag HB. Cholangiocarcinoma: the "other" liver cancer on the rise. Am J Gastroenterol 2002;97:3199-3200
5. Yamamoto J, Kosuge T, Takayama T, et al. Surgical treatment of intrahepatic cholangiocarcinoma: four patients surviving more than five years. Surgery 1992;111:617-622
6. Gores GJ. Cholangiocarcinoma: current concepts and insights. Hepatology 2003;37:961-969
7. Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis 2004;24:115-126
8. Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study. Scand J Gastroenterol 1997;32:1042-1045
9. Marsh JW, Iwatsuki S, Makowka L, et al. Orthotopic liver transplantation for primary sclerosing cholangitis. Ann Surg 1988;207:21-25
10. Stieber AC, Marino IR, Iwatsuki S, Starzl TE. Cholangiocarcinoma in sclerosing cholangitis. The role of liver transplantation. Int Surg 1989;74:1-3
11. Farrant JM, Hayllar KM, Wilkinson ML, et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991;100:1710-1717
12. Miros M, Kerlin P, Walker N, et al. Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before liver transplantation. Gut 1991;32:1369-1373
13. Nashan B, Schlitt HJ, Tusch G, et al. Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation. Hepatology 1996;23:1105-1111
14. Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996;38:610-615
15. Aadland E, Schrumpf E, Fausa O, et al. Primary sclerosing cholangitis: a long-term follow-up study. Scand J Gastroenterol 1987;22:655-664
16. Rosen CB, Nagomey DM. Cholangiocarcinoma complicating primary sclerosing cholangitis. Semin Liver Dis 1991;11:26-30
17. Wiesner RH, Porayko MK, Dickson ER, et al. Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 1992;16:1290-1299
18. Jarnagin WR, Fong Y, deMatteo RP, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 2001;234:507-519
19. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin 1996;46:5-27
20. Hejna M, Pruckmayer M, Raderer M. The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature. Eur J Cancer 1998;34:977-986
21. De Groen PC, Gores GJ, LaRusso NF, et al. Biliary tract cancers. N Engl J Med 1999;341:1368-1378
22. Campbell WL, Ferris JV, Holbert BL, et al. Biliary tract carcinoma complicating sclerosing cholangitis: evaluation with CT, cholangiography, US, and MR imaging. Radiology 1998;207:41-50
23. Foutch PG. Endobiliary cytotechniques for cancer diagnosis. Endoscopy 1996;28:712-717
24. Howell DA, Parsons WG, Jones MA, et al. Complete tissue sampling of biliary strictures at ERCP using a new device. Gastrointest Endosc 1996;43:498-501
25. de Groen PC. Cholangiocarcinoma in primary sclerosing cholangitis: who is at risk and how do we screen. Hepatology 2000;31:247-248
26. Kim H-J, Kim M-H, Myung S-J, et al. A new strategy for the application of CA 19-9 in the differentiation of pancreaticobiliary cancer: analysis using a receiver operating characteristic curve. Am J Gastroenterol 1999;94:1941-1946
27. Rashid A. Cellular and molecular biology of biliary tract cancers. Surg Oncol Clin N Am 2002;11:995-1009
28. Koprowaski H, Steplewski Z, Mitchell K, et al. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 1979;5:957-972
29. Mangani 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;43:5489-5492
30. Vestergaard EM, Hein HO, Meyer 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
31. Steinberg W. The clinical utility of the CA 19-9 tumor-associated antigen. Am J Gastroenterol 1990;85:350-355
32. Rhodes JM. Usefullness of novel tumour markers. Ann Oncol 1999;10(Suppl):S118-S121
33. Duffy MJ. CA 19-9 as a marker for gastrointestinal cancers: a review. Ann Clin Biochem 1998;35:364-370
34. Lamerz R. Role of tumour markers, cytogenetics. Ann Oncol 1999;10(Suppl):145-149
35. Akdogan M, Sazmaz N, Kyhan B, et al. Extraordinarily elevated CA 19-9 in benign conditions: a case report and review of the literature. Tumori 2001;87:337-339
36. Albert MB, Steinberg WM, Henry JP. Elevated serum levels of tumor markers CA 19-9 in acute cholangitis. Dig Dis Sci 1988;33:1223-1225
37. Patel AH, Harnois DM, Klee GG, et al. The utilità of CA 19-9 in the diagnosis of cholangiocarcinoma in patients without primary sclerosing cholangits. Am J Gastroenterol 2000;95:204-207
38. Siqueira E, Schoen RE, Silverman W, et al. Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. Gastrointest Endosc 2002;56:40-47
39. Chalasani N, Baluyut A, Ismail A, et al. Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology 2000;31:7-11
40. Lindberg B, Arnelo U, Bergquist A, et al. Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis. Endoscopy 2002;34:909-916
41. Björnsson E, Kilander A, Olsson R, et al. CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis. Liver 1999;19:501-508
42. Ramage JK, Donaghy A, Farrant JM, et al. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterology 1995;108:865-869
43. Nichols JC, Gores GJ, LaRusso NF, et al. Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis. Mayo Clin Proc 1993;68:874-879
44. Buffet C, Fourreé C, Altman C, et al. Bile levels in carcinoembryonic antigen in patients with hepatopancreaticobiliary disease. Eur J Gastroenterol Hepatol 1996;8:131-134
45. Hultcrantz R, Olsson R, Danielsson A, et al. A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. J Hepatol 1999;30:669-673
46. Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem 2001;47:624-630
47. Torzilli G, Makuushi M, Ferrero A, et al. Accuracy of the preoperafive determination of tumor markers in the differentiation of liver mass lesions in surgical patients. Hepatogastroenterology 2002;49:740-745
48. Strom BL, Iliopoulos D, Atkinson B, et al. Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease. J Natl Cancer Inst 1989;81:1575-1580
49. Ker CG, Chen JS, Lee KT, Sheen PC, Wu CC. Assessment of serum and bile levels of CA 19-9 and CA 125 in cholangitis and bile duct carcinoma. J Gastroenterol Hepatol 1991;6:505-508
50. Chen CY, Shiesh SC, Tsao HC, Lin XZ. The assessment of biliary CA 125, CA 19-9 and CEA in diagnosing cholangiocarcinoma-the influence of sampling time and hepatolithiasis. Hepatogastroenterology 2002;49:616-620
51. Ohshio G, Manabe T, Watanabe Y, et al. Comparative studies of DU-PAN-2, carcinoembryonic antigen, and CA 19-9 in the serum and bile of patients with pancreatic and biliary tract diseases: evaluation of the influence of obstructive jaundice. Am J Gastroenterol 1990;85:1370-1376
52. Tatsuta M, Iishi H, Ischii M, et al. Values of carcinoembryonic antigen, elastase 1, and carbohydrate antigen determinant in aspirated pancreatic cystic fluid in the diagnosis of cysts of the pancreas. Cancer 1986;57:1836-1839
53. Nakeeb A, Lipsett PA, Lillemoe KD, et al. Biliary carcinoembryonic antigen levels are a marker for cholangiocarcinoma. Am J Surg 1996;171:147-153
54. Akiyama H, Yamamoto M, Sumiyoshi H, Tahara E, Iwamori S. Carcinoembryonic antigen (CEA) in gallbladder bile and mucosa in cholecystolithiasis. Acta Chir Scand 1986;152:509-513
55. Plebani M, Basso D, Panozzo MP, et al. Tumor markers in the diagnosis, monitoring and therapy of pancreatic cancer: state of the art. Int J Biol Markers 1995;10:189-199
56. Kuusela P, Haglund C, Roberts PJ. Comparison of a new tumor marker CA 242 with CA 19-9, CA 50 and carcinoembryonic antigen (CEA) in digestive tract diseases. Br J Cancer 1991;63:636-640
57. Haglund C, Lindgren J, Roberts PJ, Nordling S. Difference in tissue expression of tumor markers CA 19-9 and CA 50 in hepatocellular carcinoma and cholangiocarcinoma. Br J Cancer 1991;63:386-389
58. Carpelan-Holmstróm M, Louhimo J, Stenman UH, et al. CEA, CA 19-9 and CA 72-4 improve the diagnostic accuracy in gastrointestinal cancers. Anticancer Res 2002;22:2311-2316
59. Bhargava AK, Petrelli NJ, Karna A, et al. Serum levels of cancer-associated antigen CA 195 in gastrointestinal cancers and its comparison with CA 19-9. J Clin Lab Anal 1989;3:370-377
60. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 1982;31:11-24
61. Van Eyken P, Desmet VJ. Cytokeratin expression in hepatocellular carcinoma and cholangiocarcinoma. Liver 1993;13:113-122
62. Kashihara T, Ohki A, Kobayashi T, et al. Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 levels. J Gastroenterol 1998;33:447-453
63. Uenishi T, Kubo S, Hirohashi K, et al. Cyterkeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer. Br J Cancer 2003;88:1894-1899
64. Enjoji M, Nakashima M, Nishi H, et al. The tumor associated antigen, RCAS1, can be expressed in immune-mediated diseases as well as in carcinomas of the biliary tract. J Hepatol 2002;36:786-792
65. Noguchi K, Enjoji M, Nakamuta M, et al. Expression of a tumor associated antigen RCAS1 in hepatocellular carcinoma. Cancer Lett 2001;168:197-202
66. Watanabe H, Enjoji M, Nakashima M, et al. Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma. J Hepatol 2003;39:559-563
67. Liebman HA, Furie BC, Tong MJ, et al. Des-γ-carboxy (abnormal) prothrombin as a serum marker for primary hepatocellular carcinoma. N Engl J Med 1984;310:1427-1431
68. Nakao A, Taniguchi K, Inoue S, et al. Clinical application of a new monoclonal antibody (19B7) against PIVKA-II in the diagnosis of hepatocellular carcinoma and pancreaticobiliary malignancies. Am J Gastroenterol 1997;92:1031-1034
69. Korner T, Kopf J, Hackler R, et al. Fibronectin in human bile fluid for diagnosis of malignant biliary diseases. Hepatology 1996;23:423-428
70. Chen CY, Lin XZ, Tsao HC, Shiesh SC. The value of biliary fibronectin for diagnosis of cholangiocarcinoma. Hepatogastroenterology 2003;50:924-927
71. Haglund C, Ylätupa S, Mertariemi P, Partanen P. Cellular fibronectin concentration in the plasma of patients with malignant and benign diseases: acomparison with CA-19-9 and CEA. Br J Cancer 1997;76:777-783
72. Park J, Tadlock L, Gores LJ, Patel T. Inhibition of interleukin-6 mediated mitogen-activated protein kinase activation attenuates growth of a cholangicarcinoma cell line. Hepatology 1999;30:1128-1133
73. Sugawara H, Yasoshima M, Katayanagi K, et al. Relationship between interleukin-6 and proliferation and differentiation in cholangiocarcinoma. Histopathology 1998;33:145
74. Goydos JS, Brumfield AM, Frezza E, et al. Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma. Ann Surg 1998;227:398-404
75. 1-antitrypsin in serum. Clin Chem 1994;40:1761-1765
76. 1-antitrypsin complex in malignant and benign digestive-tract diseases. Preferential elevation in patients with cholangiocarcinomas. Int J Cancer 1996;66:326-331
77. Nathan JD, Liddle RA. Neurohormonal control of pancreatic exocrine secretion. Curr Opin Gastroenterol 2002;18:536-544
78. Bruckner H, Chesser M, Mandeli J, Farber LA, DiGiovanni G. Circulating pancreatic polypeptide in patients with adenocarcinoma of the bile duct. Acta Oncol 1993;32:627-629
79. Haug H, Schramm C. Metabolic pattern of free amino acids, glucose, lactic acid, pyruvic acid, fatty acids, BUN, uric acid, etc. in serum of 21 healthy persons and 24 patients with malignant tumors. Clin Chem 1975;21:1025
80. Ohsaka A, Yoshikawa K, Matsuhashi T, et al. Detection by proton nuclear magnetic resonance of elevated lactate concentration in serums from patients with malignant tumors. Jpn J Med Sci Biol 1979;32:305-309
81. Nishijima T, Nishina M, Fujiwara K. Measurement of lactate levels in serum and bile using proton nuclear magnetic resonance in patients with hepatobiliary diseases: its utility in detection of malignancies. Jpn J Clin Oncol 1997;27:13-17
82. Barbacid M. Ras genes. Annu Rev Biochem 1987;56:779-827
83. Kang YK, Kim WH, Lee HW, et al. Mutation of p53 and k-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma. Lab Invest 1999;79:477-483
84. Isa T, Tomita S, Nakachi A, et al. Analysis of microsatellite instability, K-ras gene mutation and p53 protein overexpression in intrahepatic cholangiocarcinoma. Hepatogastroenterology 2002;49:604-608
85. Ohashi K, Nakajima Y, Kanehiro H, et al. Ki-ras mutations and p53 protein expressions in intrahepatic cholangiocarcinomas: relation to gross tumor morphology. Gastroenterology 1995;109:1612-1617
86. Tada M, Omata M, Ohto M. High incidence of ras gene mutation in intrahepatic cholangiocarcinoma. Cancer 1992;69:1115-1118
87. Furobo S, Harada K, Shimonishi T, et al. Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma. Histopathology 1999;35:230-240
88. Levi S, Urbano-Ispizua A, Gill R, et al. Multiple K-ras codon 12 mutations in cholangiocarcinoma demonstrated with a sensitive polymerase chain reaction technique. Cancer Res 1991;51:3497-3502
89. Watanabe M, Asaka M, Tanaka J, et al. Point mutation of K-ras gene codon 12 in biliary tract tumors. Gastroenterology 1994;107:1147-1153
90. Imai M, Hoshi T, Ogawa K. K-ras codon 12 mutations in biliary tract tumors detected by polymerase chain reaction denaturing gradient gel electrophoresis. Cancer 1994;73:2727-2733
91. Ohashi K, Tsutsumi M, Nakajima Y, et al. High rates of ki-ras point mutation in both intra- and extra-hepatic cholangiocarcinomas. Jpn J Clin Oncol 1994;24:305-310
92. Wattanasirichaigoon S, Tasanakhajorn U, Jesadapatarakul S. The incidence of K-ras codon 12 mutations in cholangiocarcinoma detected by polymerase chain reaction technique. J Med Assoc Thai 1998;81:316-323
93. Lee JC, Lin PW, Lin YJ, et al. Analysis of K-ras gene mutations in periampullary cancers, gallbladder cancers and cholangiocarcinomas from paraffin-embedded tissue sections. J Formos Med Assoc 1995;94:719-723
94. Tannapfel A, Benicke M, Katalinic A, et al. Frequency of p16ink4A alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver. Gut 2000;47:721-727
95. Boberg KM, Schrumpf E, Bergquist A, et al. Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations anf Tp53 dysfunction are implicated in neoplastic development. J Hepatol 2000;32:374-380
96. Kubicka S, Kühnel F, Flemming P, et al. K-ras mutations in the bile of patients with primary sclerosing cholangitis. Gut 2001;48:403-408
97. Tada M, Omata M, Kawai S, et al., Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res 1993;53:2472-2474
98. Itoi T, Takei K, Shinohara Y, et al. K-ras con 12 and p53 mutations in biopsy specimens and bile from biliary tract cancers. Pathol Int 1999;49:30-37
99. Ito R, Tamuara K, Ashida H, et al. Usefulness of k-ras gene mutation at codon 12 in bile for diagnosing biliary strictures. Int J Oncol 1998;12:1019-1023
100. Van Laethem J-L, Bourgeois V, Parma J, et al. Relative contribution of ki-ras gene analysis and brush cytology during ERCP for the diagnosis of biliary and pancreatic diseases. Gastrointest Endosc 1998;47:479-485
101. Sturm PDJ, Rauws EAJ, Hruban RH, et al. Clinical value of K-ras codon 12 analysis and endobiliary brush cytology for the diagnosis of malignant extrahepatic bile duct stenosis. Clin Cancer Res 1999;5:629-635
102. Van Heek NT, Rauws EAJ, Caspers E, et al. Long-term follow-up of patients with clinically benign extrahepatic biliary stenosis and K-ras mutation in endobiliary brush cytology. Gastrointest Endosc 2002;55:883-888
103. Wang Y, Yasushi Y, Watanabe H, et al. Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K-ras mutation. J Gastroenterol 2002;37:831-839
104. Saurin JC, Joly-Pharaboz MO, Pernas P, et al. Detection of ki-ras point mutations in bile specimens for the differential diagnosis of malignant and benign biliary strictures. Gut 2000;47:357-361
105. Müller P, Ostwald C, Püschel K, et al. Low frequency of p53 and ras mutations in bile of patients with hepato-biliary disease: a prospective study in more than 100 patients. Eur J Clin Invest 2001;31:240-247
106. Yamashita K, Yoshiki K, Shinoda H, et al. K-ras mutations in the supernatants of pancreatic juice and bile are reliable for diagnosis of pancreas and biliary tract carcinomas complementary to cytologic examination. Jpn J Cancer Res 1999;90:240-248
107. Lee JG, Leung JW, Cotton PB, et al. Diagnostic utility of k-ras mutational analysis on bile obtained by endoscopic retrograde cholangiopancreatography. Gastrointest Endosc 1995;42:317-320
108. Levine AJ, Momand J, Finlay CA. The p53 tumor suppressor gene. Nature 1991;351:453-456
109. Harris CC, Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993;329:1318-1327
110. Chang F, Syrjanen S, Syrjanen K. Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 1995;13:1009-1022
111. Tannapfel A, Sommerer F, Benicke M, et al. Genetic and epigenetic alterations of the INK4a-ARF pathway in cholangiocarcinoma. J Pathol 2002;197:624-631
112. Suto T, Habano W, Sugai T, et al. Aberrations of the K-ras, p53, and APC genes in extrahepatic bile duct cancer. J Surg Oncol 2000;73:158-163
113. Laurent-Puig P, Lubin R, Semhoun-Ducloux S, et al. Antibodies against p53 protein in serum of patients with benign or malignant pancreatic and biliary diseases. Gut 1995;36:455-458
114. Sherr CJ. Tumour surveillance via the ARF-p53 pathway. Genes Dev 1998;12:2984-2991
115. ARF. Cell 1997;91:649-659
116. Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation an all common human cancers. Cancer Res 1995;55:4525-4530
117. Liggett WH, Sidransky D. Role of the p16 tumor suppressor gene in cancer. J Clin Oncol 1998;16:1197-1206
118. Sherr CJ. Cancer cell cycles. Science 1996;276:1672-1677
119. Merlo A, Herman JG, Mao L, et al. 5′CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/CDKN2/ MTS1 in human cancers. Nat Med 1995;7:686-692
120. Kamb A. Cell-cycle regulators and cancer. Trends Genet 1995;11:136-140
121. Herman JG, Merlo A, Mao L, et al. Inactivation of the CDK/N2/p16/MTS1 gene is frequently associated with aberrant methylation in all common human cancers. Cancer Res 1995;55:4525-4530
122. Caca K, Feisthammel J, Klee K, et al. Inactivation of the INK/ARF locus and p53 in sporadic extrahepatic bile duct cancers and bile duct cancer cell lines. Int J Cancer 2002;97:481-488
123. Klump B, Hsieh C-J, Holzmann K, et al. Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barett's esophagus. Gastroenterology 1998;115:1381-1386
124. Hsieh CJ, Klump B, Holzmann K, et al. Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis. Cancer Res 1998;58:3942-3945
125. INK4 is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA 1998;95:11891-11896
126. Esteller M, Sanchez-Cespedes M, Resell R, et al. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell cancer patients. Cancer Res 1999;59:67-70
127. Carnero A, Hudson JD, Price CM, Beach DH. p16INK4 and p19ARF act in overlapping pathways in cellular immortalization. Nat Cell Biol 2000;2:148-155
128. Klump B, Hsieh CJ, Dette S, et al. Promoter methylation of INKa/ARF as detected in bile-significance for differential diagnosis in biliary disease. Clin Cancer Res 2003;9:1773-1778
129. INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma. Gastroenterology 2002;123:1090-1098
130. Rew D. Significance of aneuploidy. Br J Surg 1994;81:1416-1422
131. Rickaert F, Gelin M, van Gansbeke D, et al. Computerized morhonuclear characterisitcs and DNA content of adenocarcinoma of the pancreas, chronic pancreatitis, and normal tissues: relationship with histopathologic grading. Hum Pathol 1992;23:1210-1215
132. Ryan ME, Baldauf MC. Comparison of flow cytometry for DNA content and brush cytology for detection of malignancy in pancreaticobiliary strictures. Gastrointest Endosc 1994;40:133-139
133. Rumalla A, Baron TH, Leontovich O, et al. Improved diagnostic yield of endoscopic biliary brush cytology by digital image analysis. Mayo Clin Proc 2001;76:29-33
134. Yeaton P, Kiss R, Deviere J, et al. Use of cell image analysis in the detection of cancer from specimens obtained during endoscopic retrograde cholangiopanacreatography. Am J Clin Pathol 1993;100:497-501
135. Sears RJ, Duckworth CW, Decaestecker C, et al. Image cytometry as a discriminant tool for cytologic specimens obtained by endoscopic retrograde cholangiopancreatography. Cancer 1998;84:119-126
136. Chen XQ, Stroun M, Magnenat JL, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med 1996;2:1033-1035
137. Chang YC, Ho CL, Chen HHW, et al. Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum. Br J Cancer 2002;87:1449-1453
138. Su W-C, Shiesh S-C, Liu H-S. Expression of oncogene products HER2/Neu and ras and fibrosis-related growth factors bFGF, TGF-β, and PDGF in bile from biliary malignancies and inflammatory disorders. Dig Dis Sci 2001;46:1387-1392