Skip to main content
SpringerLink
Log in
Book cover

Biliary Tract and Gallbladder Cancer pp 99–115Cite as

Molecular Profiling

  • Chapter
  • First Online:

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

Molecular studies concerning cholangiocarcinoma (CCA) or gallbladder cancer are only at the beginning, and the epidemiologic, biologic, and pathological heterogeneity of these cancers constitutes a challenge for the future. Recent studies, in fact, highlighted how CCA is composed of different clinical–pathological subtypes with different cells of origin, pathogenesis, and risk factors. In this chapter, we discuss recent studies regarding the molecular profiling of CCA and gallbladder cancer, which aimed to clarify tumor etiopathogenesis, support diagnosis, and target treatments. Published studies have been critically analyzed taking into consideration the geographic and racial variability, and the pathologic features of the CCA.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Nakanuma Y, Sripa B, Vatanasapt V et al (2000) Intrahepatic cholangiocarcinoma. In: Hamilton SR, Aaltonen LA (eds) World Health Organization classification of tumours: pathology and genetics of tumours of the digestive system. IARC Press, Lyon, pp 173–180

    Google Scholar 

  2. Blechacz B, Komuta M, Roskams T et al (2011) Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 8:512–522

    Article  PubMed Central  PubMed  Google Scholar 

  3. Razumilava N, Gores GJ (2013) Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol 11(13–21):e1

    PubMed  Google Scholar 

  4. Cardinale V, Carpino G, Reid L et al (2012) Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity. World J Gastrointest Oncol 4:94–102

    Article  PubMed Central  PubMed  Google Scholar 

  5. Fabris L, Alvaro D (2012) The prognosis of perihilar cholangiocarcinoma after radical treatments. Hepatology 56:800–802

    Article  PubMed  Google Scholar 

  6. Fabris L, Cadamuro M, Moserle L et al (2011) Nuclear expression of S100A4 calcium-binding protein increases cholangiocarcinoma invasiveness and metastasization. Hepatology 54:890–899

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Cardinale V, Semeraro R, Torrice A et al (2010) Intra-hepatic and extra-hepatic cholangiocarcinoma: new insight into epidemiology and risk factors. World J Gastrointest Oncol 2:407–416

    Article  PubMed Central  PubMed  Google Scholar 

  8. Bragazzi MC, Cardinale V, Carpino G et al (2012) Cholangiocarcinoma: epidemiology and risk factors. Transl Gastrointest Cancer 1:21–32. doi:10.3978/j.issn.2224-4778.2011.11.04

    Google Scholar 

  9. Khan SA, Davidson BR, Goldin RD et al (2012) Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut 61:1657–1669

    Article  PubMed  CAS  Google Scholar 

  10. Nault JC, Zucman-Rossi J (2011) Genetics of hepatobiliary carcinogenesis. Semin Liver Dis 31:173–187

    Article  PubMed  CAS  Google Scholar 

  11. Gatto M, Alvaro D (2010) New insights on cholangiocarcinoma. World J Gastrointest Oncol 2:136–145

    Article  PubMed Central  PubMed  Google Scholar 

  12. Chen CP, Haas-Kogan D (2010) Neoplasms of the hepatobiliary system: clinical presentation, molecular pathways and diagnostics. Expert Rev Mol Diagn 10:883–895

    Article  PubMed  CAS  Google Scholar 

  13. Alvaro D (2011) Progranulin and cholangiocarcinoma: another bad boy on the block! Gut 61:170–171

    Article  PubMed  Google Scholar 

  14. Hainsworth JD, Rubin MS, Spigel DR et al (2013) Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah cannon research institute. J Clin Oncol 31:217–223

    Article  PubMed  CAS  Google Scholar 

  15. Ismael G, de Azambuja E, Awada A (2006) Molecular profiling of a tumor of unknown origin. N Engl J Med 355:1071–1072

    Article  PubMed  CAS  Google Scholar 

  16. Ioannidis JP (2007) Is molecular profiling ready for use in clinical decision making? Oncologist 12:301–311

    Article  PubMed  Google Scholar 

  17. Kumar M, Zhao X, Wang XW et al (2012) Molecular carcinogenesis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: one step closer to personalized medicine? Hepatology 56:800–802

    Article  Google Scholar 

  18. Khan SA, Thomas HC, Toledano MB et al (2005) p53 Mutations in human cholangiocarcinoma: a review. Liver Int 25:704–716

    Article  PubMed  CAS  Google Scholar 

  19. Kamikawa T, Amenomori M, Itoh T et al (1999) Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast. Radiat Res 152:S118–S124

    Article  PubMed  CAS  Google Scholar 

  20. Kiba T, Tsuda H, Pairojkul C et al (1993) Mutations of the p53 tumor suppressor gene and the ras gene family in intrahepatic cholangiocellular carcinomas in Japan and Thailand. Mol Carcinog 8:312–318

    Article  PubMed  CAS  Google Scholar 

  21. Petmitr S, Pinlaor S, Thousungnoen A et al (1998) K-ras oncogene and p53 gene mutations in human cholangiocarcinoma from Thai patients. Southeast Asian J Trop Med Public Health 29:71–75

    PubMed  CAS  Google Scholar 

  22. Sturm PD, Baas IO, Clement MJ et al (1998) Alterations of the p53 tumor-suppressor gene and K-ras oncogene in perihilar cholangiocarcinomas from a high-incidence area. Int J Cancer 78:695–698

    Article  PubMed  CAS  Google Scholar 

  23. Jonas S, Springmeier G, Tauber R et al (1998) p53 mutagenesis in Klatskin tumors. Hum Pathol 29:955–960

    Article  PubMed  CAS  Google Scholar 

  24. Kang YK, Kim WH, Lee HW et al (1999) Mutation of p53 and K-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma. Lab Invest 79:477–483

    PubMed  CAS  Google Scholar 

  25. Furubo S, Harada K, Shimonishi T et al (1999) Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma. Histopathology 35:230–240

    Article  PubMed  CAS  Google Scholar 

  26. Della Torre G, Pasquini G, Pilotti S et al (2000) TP53 mutations and mdm2 protein overexpression in cholangiocarcinomas. Diagn Mol Pathol 9:41–46

    Article  PubMed  CAS  Google Scholar 

  27. Tullo A, D’Erchia AM, Honda K et al (2000) New p53 mutations in hilar cholangiocarcinoma. Eur J Clin Invest 30:798–803

    Article  PubMed  CAS  Google Scholar 

  28. Momoi H, Itoh T, Nozaki Y et al (2001) Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma. J Hepatol 35:235–244

    Article  PubMed  CAS  Google Scholar 

  29. Liu XF, Zhang H, Zhu SG et al (2006) Correlation of p53 gene mutation and expression of P53 protein in cholangiocarcinoma. World J Gastroenterol 12:4706–4709

    PubMed  CAS  Google Scholar 

  30. Imai Y, Oda H, Arai M et al (1996) Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hepatocellular-cholangiocellular carcinomas. Jpn J Cancer Res 87:1056–1062

    Article  PubMed  CAS  Google Scholar 

  31. Itoi T, Takei K, Shinohara Y et al (1999) K-ras codon 12 and p53 mutations in biopsy specimens and bile from biliary tract cancers. Pathol Int 49:30–37

    Article  PubMed  CAS  Google Scholar 

  32. Lai GH, Zhang Z, Shen XN et al (2005) erbB-2/neu transformed rat cholangiocytes recapitulate key cellular and molecular features of human bile duct cancer. Gastroenterology 129:2047–2057

    Article  PubMed  CAS  Google Scholar 

  33. Aishima SI, Taguchi KI, Sugimachi K et al (2002) c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma. Histopathology 40:269–278

    Article  PubMed  Google Scholar 

  34. Andersen JB, Thorgeirsson SS (2012) Genetic profiling of intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol 28:266–272

    Article  PubMed  CAS  Google Scholar 

  35. Tada M, Omata M, Ohto M (1992) High incidence of ras gene mutation in intrahepatic cholangiocarcinoma. Cancer 69:1115–1118

    Article  PubMed  CAS  Google Scholar 

  36. Ohashi K, Nakajima Y, Kanehiro H et al (1995) Ki-ras mutations and p53 protein expressions in intrahepatic cholangiocarcinomas: relation to gross tumor morphology. Gastroenterology 109:1612–1617

    Article  PubMed  CAS  Google Scholar 

  37. Tannapfel A, Benicke M, Katalinic A et al (2000) Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver. Gut 47:721–727

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Ahrendt SA, Rashid A, Chow JT et al (2000) p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer. J Hepatobiliary Pancreat Surg 7:426–431

    Article  PubMed  CAS  Google Scholar 

  39. Xu RF, Sun JP, Zhang SR et al (2011) KRAS and PIK3CA but not BRAF genes are frequently mutated in Chinese cholangiocarcinoma patients. Biomed Pharmacother 65:22–26

    Article  PubMed  CAS  Google Scholar 

  40. Rashid A, Ueki T, Gao YT et al (2002) K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China. Clin Cancer Res 8:3156–3163

    PubMed  CAS  Google Scholar 

  41. Isa T, Tomita S, Nakachi A et al (2002) Analysis of microsatellite instability, K-ras gene mutation and p53 protein overexpression in intrahepatic cholangiocarcinoma. Hepato-gastroenterology 49(45):604–608

    Google Scholar 

  42. Komori J, Marusawa H, Machimoto T et al (2008) Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. Hepatology 47:888–896

    Article  PubMed  CAS  Google Scholar 

  43. Borger DR, Tanabe KK, Fan KC et al (2012) Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 17:72–79

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Isomoto H, Mott JL, Kobayashi S et al (2007) Sustained IL-6/STAT-3 signaling in cholangiocarcinoma cells due to SOCS-3 epigenetic silencing. Gastroenterology 132:384–396

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Sandhu DS, Shire AM, Roberts LR (2008) Epigenetic DNA hypermethylation in cholangiocarcinoma: potential roles in pathogenesis, diagnosis and identification of treatment targets. Liver Int 28:12–27

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  46. Isomoto H, Kobayashi S, Werneburg NW et al (2005) Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells. Hepatology 42:1329–1338

    Article  PubMed  CAS  Google Scholar 

  47. Kobayashi S, Werneburg NW, Bronk SF et al (2005) Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells. Gastroenterology 128:2054–2065

    Article  PubMed  CAS  Google Scholar 

  48. Kim SH, Ricci MS, El-Deiry WS (2008) Mcl-1: a gateway to TRAIL sensitization. Cancer Res 68:2062–2064

    Article  PubMed  CAS  Google Scholar 

  49. Frampton G, Invernizzi P, Bernuzzi F et al (2012) Interleukin-6- driven progranulin expression increases cholangiocarcinoma growth by an Akt dependent mechanism. Gut 61:268–277

    Article  PubMed  CAS  Google Scholar 

  50. Endo K, Yoon BI, Pairojkul C et al (2002) ERBB-2 overexpression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions. Hepatology 36:439–450

    Article  PubMed  CAS  Google Scholar 

  51. Jaiswal M, LaRusso NF, Burgart LJ et al (2000) Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 60:184–190

    PubMed  CAS  Google Scholar 

  52. Alvaro D, Barbaro B, Franchitto A et al (2006) Estrogens and insulin-like growth factor 1 modulate neoplastic cell growth in human cholangiocarcinoma. Am J Pathol 169:877–888

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Mancino A, Mancino MG, Glaser SS et al (2009) Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor. Dig Liver Dis 41:156–163

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Alvaro D, Macarri G, Mancino MG et al (2007) Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. Ann Intern Med 147:451–459

    Article  PubMed  Google Scholar 

  55. McKay SC, Unger K, Pericleous S et al (2011) Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma. HPB (Oxford) 13:309–319

    Article  Google Scholar 

  56. Seol MA, Chu IS, Lee MJ et al (2011) Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma. BMC Cancer 11:78. doi: 10.1086/1471-2407-11-78

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  57. Andersen JB, Spee B, Blechacz BR et al (2012) Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors. Gastroenterology 142:1021–1031

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  58. Kipp BR, Fritcher EG, Clayton AC et al (2010) Comparison of KRAS mutation analysis and FISH for detecting pancreatobiliary tract cancer in cytology specimens collected during endoscopic retrograde cholangiopancreatography. J Mol Diagn 12:780–786

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Huang L, Frampton G, Liang LJ et al (2010) Aberrant DNA methylation profile in cholangiocarcinoma. World J Gastrointest Pathophysiol 1:23–29

    Article  PubMed Central  PubMed  Google Scholar 

  60. Huang L, Frampton G, Rao A et al (2012) Monoamine oxidase a expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events. Lab Invest 92:1451–1460

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Sakoda LC, Gao YT, Chen BE et al (2006) Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China. Carcinogenesis 27:1251–1256

    Article  PubMed  CAS  Google Scholar 

  62. Sripa B, Kaewkes S, Sithithaworn P et al (2007) Liver fluke induces cholangiocarcinoma. PLoS Med 4:e201

    Article  PubMed Central  PubMed  Google Scholar 

  63. Jinawath N, Chamgramol Y, Furukawa Y et al (2006) Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma. Hepatology 44:1025–1038

    Article  PubMed  CAS  Google Scholar 

  64. Wang X, Chen W, Huang Y et al (2011) The draft genome of the carcinogenic human liver fluke Clonorchis sinensis. Genome Biol 12:R107

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Young ND, Campbell BE, Hall RS et al (2010) Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini. PLoS Negl Trop Dis 4:e719. doi:10.1371/journal.pntd.0000719

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Sriraksa R, Zeller C, El-Bahrawy MA et al (2011) CpG-island methylation study of liver fluke-related cholangiocarcinoma. Br J Cancer 104:1313–1318

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  67. Melum E, Karlsen TH, Schrumpf E et al (2008) Cholangiocarcinoma in primary sclerosing cholangitis is associated with NKG2D polymorphisms. Hepatology 47:90–96

    Article  PubMed  CAS  Google Scholar 

  68. Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nature Rev Genetics 10(1):57–63

    Article  CAS  Google Scholar 

  69. Hansel DE, Rahman A, Hidalgo M et al (2003) Identification of novel cellular targets in biliary tract cancers using global gene expression technology. Am J Pathol 163(1):217–229

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  70. Obama K, Ura K, Li M et al (2005) Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma. Hepatology 41:1339–1348

    Article  PubMed  CAS  Google Scholar 

  71. Hass HG, Nehls O, Jobst J et al (2008) Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: detection by oligonucleotide microarray and real-time PCR analysis. World J Gastroenterol 14:2501–2510

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  72. Carpino G, Cardinale V, Reid L et al (2012) Cells of origin and cancer stem cells in cholangiocarcinoma. Transl Gastrointest Cancer 1:33–43

    Google Scholar 

  73. Roskams T (2006) Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene 25:3818–3822

    Article  PubMed  CAS  Google Scholar 

  74. Tannapfel A, Sommerer F, Benicke M et al (2003) Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma. Gut 52:706–712

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Tan FL, Ooi A, Huang D et al (2010) p38delta/MAPK13 as a diagnostic marker for cholangiocarcinoma and its involvement in cell motility and invasion. Int J Cancer 126:2353–2361

    PubMed  CAS  Google Scholar 

  76. Terada T, Nakanuma Y (1996) Expression of apoptosis, proliferating cell nuclear antigen, and apoptosis-related antigens (bcl-2, c-myc, Fas, Lewis(y) and p53) in human cholangiocarcinomas and hepatocellular carcinomas. Pathol Int 46:764–770

    Article  PubMed  CAS  Google Scholar 

  77. Chapman MH, Tidswell R, Dooley JS et al (2011) Whole genome RNA expression profiling of endoscopic biliary brushings provides data suitable for biomarker discovery in cholangiocarcinoma. Genome Biol 12:R107

    Article  CAS  Google Scholar 

  78. Finkelstein SD, Bibbo M, Loren DE et al (2012) Molecular analysis of centrifugation supernatant fluid from pancreaticobiliary duct samples can improve cancer detection. Acta Cytol 56:439–447

    Article  PubMed  CAS  Google Scholar 

  79. Malouf G, Dreyer C, Guedj N et al (2009) Prognosis factors of cholangiocarcinoma: contribution of recent molecular biology tools. Bull Cancer 96:405–415

    PubMed  CAS  Google Scholar 

  80. Utispan K, Thuwajit P, Abiko Y et al (2010) Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker. Mol Cancer 9:13

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  81. Murakawa K, Tada M, Takada M et al (2004) Prediction of lymph node metastasis and perineural invasion of biliary tract cancer by selected features from cDNA array data. J Surg Res 122:184–194

    Article  PubMed  CAS  Google Scholar 

  82. Sia D, Hoshida Y, Villanueva A et al (2013) Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes. Gastroenterology. doi:10.1053/j.gastro.2013.01.001

    PubMed  PubMed Central  Google Scholar 

  83. Oikawa T, Kamiya A, Zeniya M et al (2012) SALL4, a stem cell biomarker in liver cancers. Hepatology. doi:10.1002/hep.26147

  84. Oishi N, Kumar MR, Roessler S et al (2012) Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma. Hepatology 56:1792–1803

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. He XR, Wu XP (2008) et al Difference in biological characteristics and sensitivity to chemotherapy and radiotherapy between intrahepatic and extrahepatic cholangiocarcinoma cells in vitro. Chin Med Sci J 23:54–59

    Article  PubMed  CAS  Google Scholar 

  86. Guedj N, Zhan Q, Perigny M (2009) et al. Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas. J Hepatol 51:93–101

    Article  PubMed  CAS  Google Scholar 

  87. Karamitopoulou E, Tornillo L, Zlobec I et al (2008) Clinical significance of cell cycle- and apoptosis-related markers in biliary tract cancer: a tissue microarray-based approach revealing a distinctive immunophenotype for intrahepatic and extrahepatic cholangiocarcinomas. Am J Clin Pathol 130:780–786

    Article  PubMed  CAS  Google Scholar 

  88. Miller G, Socci ND, Dhall D et al (2009) Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract. J Exp Clin Cancer Res 28:62

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  89. Yang B, House MG, Guo M et al (2005) Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol 18:412–420

    Article  PubMed  CAS  Google Scholar 

  90. Nakanuma Y, Sato Y, Harada K et al (2010) Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol 2:419–427

    Article  PubMed Central  PubMed  Google Scholar 

  91. Komuta M, Govaere O, Vandecaveye V et al (2012) Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology 55:1876–1888

    Article  PubMed  CAS  Google Scholar 

  92. Ueno Y, Alpini G, Yahagi K et al (2003) Evaluation of differential gene expression by microarray analysis in small and large cholangiocytes isolated from normal mice. Liver Int 23:449–459

    Article  PubMed  CAS  Google Scholar 

  93. Schmelzer E, Zhang L, Bruce A et al (2007) Human hepatic stem cells from fetal and postnatal donors. J Exp Med 204:1973–1987

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  94. Turner R, Lozoya O, Wang Y et al (2011) Human hepatic stem cell and maturational liver lineage biology. Hepatology 53:1035–1045

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  95. Cardinale V, Wang Y, Carpino G et al (2011) Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets. Hepatology 54:2159–2172

    Article  PubMed  CAS  Google Scholar 

  96. Cardinale V, Wang Y, Carpino G et al (2012) The biliary tree—a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 9(4):231–240

    Article  PubMed  CAS  Google Scholar 

  97. Aishima S, Kuroda Y, Nishihara Y et al (2007) Proposal of progression model for intrahepatic cholangiocarcinoma: clinicopathologic differences between hilar type and peripheral type. Am J Surg Pathol 31:1059–1067

    Article  PubMed  Google Scholar 

  98. Lee JS, Heo J, Libbrecht L et al (2006) A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 12:410–416

    Article  PubMed  CAS  Google Scholar 

  99. Komuta M, Spee B, Vander Borght S et al (2008) Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology 47:1544–1556

    Article  PubMed  CAS  Google Scholar 

  100. Yokoyama N, Hitomi J, Watanabe H et al (1998) Mutations of p53 in gallbladder carcinomas in high-incidence areas of Japan and Chile. Cancer Epidemiol Biomarkers Prev 7:297–301. doi: 10.1186/1471-2407-11-78

    PubMed  CAS  Google Scholar 

  101. Nigam P, Misra U, Negi TS et al (2010) Alterations of p53 gene in gallbladder cancer patients of North India. Trop Gastroenterol 31:96–100

    PubMed  Google Scholar 

  102. Kim YT, Kim J, Jang YH et al (2001) Genetic alterations in gallbladder adenoma, dysplasia and carcinoma. Cancer Lett 169:59–68

    Article  PubMed  CAS  Google Scholar 

  103. Nagahashi M, Ajioka Y, Lang I et al (2008) Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary. World J Gastroenterol 14:70–75

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  104. Imai M, Hoshi T, Ogawa K (1994) K-ras codon 12 mutations in biliary tract tumors detected by polymerase chain reaction denaturing gradient gel electrophoresis. Cancer 73:2727–2733

    Article  PubMed  CAS  Google Scholar 

  105. Ajiki T, Fujimori T, Onoyama H et al (1996) K-ras gene mutation in gall bladder carcinomas and dysplasia. Gut 38:426–429

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  106. Hanada K, Tsuchida A, Iwao T et al (1999) Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct. Am J Gastroenterol 94:1638–1642

    Article  PubMed  CAS  Google Scholar 

  107. Saetta AA, Papanastasiou P, Michalopoulos NV et al (2004) Mutational analysis of BRAF in gallbladder carcinomas in association with K-ras and p53 mutations and microsatellite instability. Virchows Arch 445:179–182

    Article  PubMed  CAS  Google Scholar 

  108. Parwani AV, Geradts J, Caspers E et al (2003) Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions. Mod Pathol 16:299–308

    Article  PubMed  Google Scholar 

  109. Pai RK, Mojtahed K, Pai RK et al (2011) Mutations in the RAS/RAF/MAP kinase pathway commonly occur in gallbladder adenomas but are uncommon in gallbladder adenocarcinomas. Appl Immunohistochem Mol Morphol 19:133–140

    Article  PubMed  CAS  Google Scholar 

  110. Pramanik V, Sarkar BN, Kar M et al (2011) A novel polymorphism in codon 25 of the KRAS gene associated with gallbladder carcinoma patients of the eastern part of India. Genet Test Mol Biomarkers 15:431–434

    Article  PubMed  CAS  Google Scholar 

  111. Kimura Y, Furuhata T, Mukaiya M et al (2011) Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma. Frequent beta-catenin alteration in gallbladder carcinomas. BMC Cancer 11:60

    Article  Google Scholar 

  112. Tan Y, Meng HP, Wu Q et al (2010) Proteomic study of gallbladder cancer, with special reference on the expression and significance of annexin A3. Zhonghua Bing Li Xue Za Zhi 39:382–386

    PubMed  CAS  Google Scholar 

  113. Alvarez H, Corvalan A, Roa JC et al (2008) Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer. Clin Cancer Res 14:2631–2638

    Article  PubMed  CAS  Google Scholar 

  114. Ikeda T, Nakayama Y, Hamada Y et al (2009) FU-MK-1 expression in human gallbladder carcinoma: an antigenic prediction marker for a better postsurgical prognosis. Am J Clin Pathol 132:111–117

    Article  PubMed  CAS  Google Scholar 

  115. Shi C, Tian R, Wang M et al (2010) CD44+ CD133+ population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. Cancer Biol Ther 10:1182–1190

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medico-Surgical Sciences and Biotechnologies, Pontino, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University of Rome, Viale dell’Università 37, 00185, Rome, Italy

    Domenico Alvaro & Vincenzo Cardinale

Authors
  1. Domenico Alvaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincenzo Cardinale
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Domenico Alvaro .

Editor information

Editors and Affiliations

  1. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland, USA

    Joseph M. Herman

  2. Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA

    Timothy M. Pawlik

  3. Department of Radiation Oncology, Oregon Health and Science University, Portland, Oregon, USA

    Charles R. Thomas, Jr.

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Alvaro, D., Cardinale, V. (2014). Molecular Profiling. In: Herman, J., Pawlik, T., Thomas, Jr., C. (eds) Biliary Tract and Gallbladder Cancer. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40558-7_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-40558-7_7

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-40557-0

  • Online ISBN: 978-3-642-40558-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation