Recent advances in cytogenetics and molecular biology of adult hepatocellular tumors: Implications for imaging and management

Radiology

Volumn 258, Issue 3, 2011, Pages 673-693

  Shanbhogue, Alampady K ^a   Prasad, Srinivasa R ^a   Takahashi, Naoki ^b   Vikram, Raghunandan ^c   Sahani, Dushyant V ^d  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^b MAYO CLINIC   (United States)

^c UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; ANGIOPOIETIN; BEVACIZUMAB; BRIVANIB; CETUXIMAB; CIXUTUMUMAB; DASATINIB; ECHOVIST; ERLOTINIB; EVEROLIMUS; FERUCARBOTRAN; FLAVOPIRIDOL; GADOBENATE DIMEGLUMINE; GADOXETIC ACID; GEFITINIB; IMATINIB; LAPATINIB; OBLIMERSEN; RAPAMYCIN; SELUMETINIB; SORAFENIB; SUNITINIB; VANDETANIB;

ADULT; ANTINEOPLASTIC ACTIVITY; CANCER INCIDENCE; CHEMOEMBOLIZATION; COMPUTER ASSISTED TOMOGRAPHY; CYTOGENETICS; DIFFERENTIAL DIAGNOSIS; ECHOGRAPHY; FIBROLAMELLAR HEPATOCELLULAR CARCINOMA; GENE MUTATION; GENETIC ASSOCIATION; HEPATOGRAPHY; HUMAN; LIVER ADENOMA; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER FOCAL NODULAR HYPERPLASIA; LIVER SURGERY; LIVER TUMOR; METABOLIC SYNDROME X; MOLECULAR BIOLOGY; MOLECULARLY TARGETED THERAPY; NUCLEAR MAGNETIC RESONANCE IMAGING; ONCOGENE; PRIORITY JOURNAL; PROGNOSIS; RADIOFREQUENCY ABLATION; REVIEW; RISK FACTOR; TUMOR CLASSIFICATION;

ADENOMA, LIVER CELL; ADULT; ANTINEOPLASTIC AGENTS; BENZENESULFONATES; CARCINOMA, HEPATOCELLULAR; CYTOGENETIC ANALYSIS; FOCAL NODULAR HYPERPLASIA; GENETIC ASSOCIATION STUDIES; HUMANS; LIVER NEOPLASMS; MAGNETIC RESONANCE IMAGING; MUTATION; PYRIDINES; TOMOGRAPHY, X-RAY COMPUTED;

EID: 79952287151     PISSN: 00338419     EISSN: 15271315     Source Type: Journal    
DOI: 10.1148/radiol.10100376     Document Type: Review

References (155)

1. Zucman-Rossi J, Jeannot E, Nhieu JT, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology 2006;43(3):515-524.
2. Bioulac-Sage P, Laumonier H, Couchy G, et al. Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology 2009;50(2):481-489.
3. Boyault S, Rickman DS, de Reyniès A, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 2007;45(1):42-52. (Pubitemid 46144363)
4. Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 1991;350(6317):429-431. (Pubitemid 21912246)
5. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378-390.
6. Vilgrain V. Focal nodular hyperplasia. Eur J Radiol 2006;58(2):236-245.
7. Mathieu D, Vilgrain V, Mahfouz AE, Anglade MC, Vullierme MP, Denys A. Benign liver tumors. Magn Reson Imaging Clin N Am 1997;5(2):255-288. (Pubitemid 27214857)
8. Cherqui D, Rahmouni A, Charlotte F, et al. Management of focal nodular hyperplasia and hepatocellular adenoma in young women: a series of 41 patients with clinical, radiological, and pathological correlations. Hepatology 1995;22(6):1674-1681.
9. Di Stasi M, Caturelli E, De Sio I, Salmi A, Buscarini E, Buscarini L. Natural history of focal nodular hyperplasia of the liver: an ultrasound study. J Clin Ultrasound 1996;24(7):345-350. (Pubitemid 26274780)
10. Kehagias D, Moulopoulos L, Antoniou A, et al. Focal nodular hyperplasia: imaging findings. Eur Radiol 2001;11(2):202-212. (Pubitemid 32755437)
11. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997;277(5322):55-60. (Pubitemid 27450643)
12. Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996;87(7):1171-1180. (Pubitemid 27010101)
13. Wanless IR, Sapp H, Guindi M, Olshansky D, Takayama A. The pathogenesis of focal nodular hyperplasia: an hypothesis based on histologic review of 20 lesions including 3 occurring in early biliary cirrhosis [abstr]. Hepatology 2006;44(4):491A.
14. Ijichi H, Taketomi A, Yoshizumi T, et al. Hyperbaric oxygen induces vascular endothelial growth factor and reduces liver injury in regenerating rat liver after partial hepatectomy. J Hepatol 2006;45(1):28-34. (Pubitemid 43850611)
15. Sato Y, Harada K, Ikeda H, et al. Hepatic stellate cells are activated around central scars of focal nodular hyperplasia of the liver - a potential mechanism of central scar formation. Hum Pathol 2009;40(2):181-188.
16. Mathieu D, Kobeiter H, Maison P, et al. Oral contraceptive use and focal nodular hyperplasia of the liver. Gastroenterology 2000;118(3):560-564. (Pubitemid 30140854)
17. Rebouissou S, Bioulac-Sage P, Zucman-Rossi J. Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma. J Hepatol 2008;48(1):163-170.
18. Rebouissou S, Couchy G, Libbrecht L, et al. The beta-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules. J Hepatol 2008;49(1):61-71.
19. Mortelé KJ, Praet M, Van Vlierberghe H, Kunnen M, Ros PR. CT and MR imaging findings in focal nodular hyperplasia of the liver: radiologic-pathologic correlation. AJR Am J Roentgenol 2000;175(3):687-692.
20. Zech CJ, Grazioli L, Breuer J, Reiser MF, Schoenberg SO. Diagnostic performance and description of morphological features of focal nodular hyperplasia in Gd-EOB-DTPA-enhanced liver magnetic resonance imaging: results of a multicenter trial. Invest Radiol 2008;43(7):504-511.
21. Rosenberg L. The risk of liver neoplasia in relation to combined oral contraceptive use. Contraception 1991;43(6):643-652.
22. Nime F, Pickren JW, Vana J, Aronoff BL, Baker HW, Murphy GP. The histology of liver tumors in oral contraceptive users observed during a national survey by the American College of Surgeons Commission on Cancer. Cancer 1979;44(4):1481-1489.
23. González A, Canga F, Cárdenas F, et al. An unusual case of hepatic adenoma in a male. J Clin Gastroenterol 1994;19(2):179-181. (Pubitemid 24267582)
24. Carrasco D, Barrachina M, Prieto M, Berenguer J. Clomiphene citrate and liver-cell adenoma. N Engl J Med 1984;310(17):1120-1121. (Pubitemid 14131510)
25. Dokmak S, Paradis V, Vilgrain V, et al. A single-center surgical experience of 122 patients with single and multiple hepatocellular adenomas. Gastroenterology 2009;137(5):1698-1705.
26. Vázquez JJ, Marigil MA. Liver-cell adenoma in an epileptic man on barbiturates. Histol Histopathol 1989;4(3):301-303. (Pubitemid 19177947)
27. Zucman-Rossi J. Genetic alterations in hepatocellular adenomas: recent findings and new challenges. J Hepatol 2004;40(6):1036-1039. (Pubitemid 38670142)
28. Bioulac-Sage P, Laumonier H, Laurent C, Zucman-Rossi J, Balabaud C. Hepatocellular adenoma: what is new in 2008. Hepatol Int 2008;2(3):316-321.
29. Bioulac-Sage P, Rebouissou S, Thomas C, et al. Hepatocellular adenoma subtype classifi cation using molecular markers and immunohistochemistry. Hepatology 2007;46(3):740-748.
30. Rebouissou S, Amessou M, Couchy G, et al. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours. Nature 2009;457(7226):200-204.
31. Spannbauer MM, Trautwein C. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumors. Hepatology 2009;49(4):1387-1389.
32. Laumonier H, Bioulac-Sage P, Laurent C, Zucman-Rossi J, Balabaud C, Trillaud H. Hepatocellular adenomas: magnetic resonance imaging features as a function of molecular pathological classification. Hepatology 2008;48(3):808-818.
33. Shih DQ, Bussen M, Sehayek E, et al. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet 2001;27(4):375-382. (Pubitemid 32268417)
34. Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D. Estrogens as endogenous genotoxic agents - DNA adducts and mutations. J Natl Cancer Inst Monogr 2000(27):75-93.
35. Rebouissou S, Imbeaud S, Balabaud C, et al. HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation. J Biol Chem 2007;282(19):14437-14446. (Pubitemid 47100455)
36. Yamagata K, Furuta H, Oda N, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 1996;384(6608):458-460. (Pubitemid 26414661)
37. Bacq Y, Jacquemin E, Balabaud C, et al. Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation. Gastroenterology 2003;125(5):1470-1475. (Pubitemid 37409767)
38. Chen ZM, Crone KG, Watson MA, Pfeifer JD, Wang HL. Identification of a unique gene expression signature that differentiates hepatocellular adenoma from well-differentiated hepatocellular carcinoma. Am J Surg Pathol 2005;29(12):1600-1608.
39. Lee PJ. Glycogen storage disease type I: pathophysiology of liver adenomas. Eur J Pediatr 2002;161(suppl 1):S46-S49.
40. Kishnani PS, Chuang TP, Bali D, et al. Chromosomal and genetic alterations in human hepatocellular adenomas associated with type Ia glycogen storage disease. Hum Mol Genet 2009;18(24):4781-4790.
41. De Souza AT, Hankins GR, Washington MK, Fine RL, Orton TC, Jirtle RL. Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. Oncogene 1995;10(9):1725-1729.
42. Yamada T, De Souza AT, Finkelstein S, Jirtle RL. Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis. Proc Natl Acad Sci U S A 1997;94(19):10351-10355. (Pubitemid 27407045)
43. Cassiman D, Libbrecht L, Verslype C, et al. An adult male patient with multiple adenomas and a hepatocellular carcinoma: mild glycogen storage disease type Ia. J Hepatol 2010;53(1):213-217.
44. Flejou JF, Barge J, Menu Y, et al. Liver adenomatosis. An entity distinct from liver adenoma? Gastroenterology 1985;89(5):1132-1138.
45. Lewin M, Handra-Luca A, Arrivé L, et al. Liver adenomatosis: classification of MR imaging features and comparison with pathologic findings. Radiology 2006;241(2):433-440. (Pubitemid 44632889)
46. Greaves WO, Bhattacharya B. Hepatic adenomatosis. Arch Pathol Lab Med 2008;132(12):1951-1955.
47. Veteläinen R, Erdogan D, de Graaf W, et al. Liver adenomatosis: re-evaluation of aetiology and management. Liver Int 2008;28(4):499-508. (Pubitemid 351411136)
48. Erdogan D, Busch OR, van Delden OM, Ten Kate FJ, Gouma DJ, van Gulik TM. Management of spontaneous haemorrhage and rupture of hepatocellular adenomas. A single centre experience. Liver Int 2006;26(4):433-438.
49. Stoot JH, van der Linden E, Terpstra OT, Schaapherder AF. Life-saving therapy for haemorrhaging liver adenomas using selective arterial embolization. Br J Surg 2007;94(10):1249-1253. (Pubitemid 47584774)
50. Terkivatan T, de Wilt JH, de Man RA, van Rijn RR, Tilanus HW, IJzermans JN. Treatment of ruptured hepatocellular adenoma. Br J Surg 2001;88(2):207-209. (Pubitemid 32142706)
51. Marini P, Vilgrain V, Belghiti J. Management of spontaneous rupture of liver tumours. Dig Surg 2002;19(2):109-113. (Pubitemid 34458055)
52. van der Sluis FJ, Bosch JL, Terkivatan T, de Man RA, Ijzermans JN, Hunink MG. Hepatocellular adenoma: cost-effectiveness of different treatment strategies. Radiology 2009;252(3):737-746.
53. Longerich T, Schirmacher P. A new link between cancer and inflammation? J Hepatol 2009;51(1):230-232.
54. Ribeiro A, Burgart LJ, Nagorney DM, Gores GJ. Management of liver adenomatosis: results with a conservative surgical approach. Liver Transpl Surg 1998;4(5):388-398. (Pubitemid 28413240)
55. Chiche L, Dao T, Salamé E, et al. Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature. Ann Surg 2000;231(1):74-81. (Pubitemid 30043942)
56. Leese T, Farges O, Bismuth H. Liver cell adenomas. A 12-year surgical experience from a specialist hepato-biliary unit. Ann Surg 1988;208(5):558-564.
57. Cobey FC, Salem RR. A review of liver masses in pregnancy and a proposed algorithm for their diagnosis and management. Am J Surg 2004;187(2):181-191. (Pubitemid 38183430)
58. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139(10):817-823.
59. Blum HE. Hepatocellular carcinoma: therapy and prevention. World J Gastroenterol 2005;11(47):7391-7400. (Pubitemid 43126017)
60. Coleman WB. Mechanisms of human hepatocarcinogenesis. Curr Mol Med 2003;3(6):573-588. (Pubitemid 37168599)
61. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001;37(suppl 8):S4-S66.
62. Freeman AJ, Dore GJ, Law MG, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 2001;34(4 pt 1):809-816.
63. Wong R, Corley DA. Racial and ethnic variations in hepatocellular carcinoma incidence within the United States. Am J Med 2008;121(6):525-531. (Pubitemid 351694349)
64. El-Serag HB. Epidemiology of hepatocellular carcinoma in USA. Hepatol Res 2007;37(suppl 2):S88-S94.
65. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127(5 suppl 1):S35-S50. (Pubitemid 39423368)
66. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130(3):678-686. (Pubitemid 43374518)
67. Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 2000;31(3):777-782. (Pubitemid 30118650)
68. Paradis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 2009;49(3):851-859.
69. Satyanarayana A, Manns MP, Rudolph KL. Telomeres, telomerase and cancer: an endless search to target the ends. Cell Cycle 2004;3(9):1138-1150. (Pubitemid 40268632)
70. Plentz RR, Caselitz M, Bleck JS, et al. Hepatocellular telomere shortening correlates with chromosomal instability and the development of human hepatoma. Hepatology 2004;40(1):80-86. (Pubitemid 38868926)
71. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115(2):209-218. (Pubitemid 40385459)
72. Mise K, Tashiro S, Yogita S, et al. Assessment of the biological malignancy of hepatocellular carcinoma: relationship to clinicopathological factors and prognosis. Clin Cancer Res 1998;4(6):1475-1482. (Pubitemid 28265231)
73. Hainaut P, Hernandez T, Robinson A, et al. IARC Database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualisation tools. Nucleic Acids Res 1998;26(1):205-213. (Pubitemid 28291534)
74. Parada LA, Hallén M, Tranberg KG, et al. Frequent rearrangements of chromosomes 1, 7, and 8 in primary liver cancer. Genes Chromosomes Cancer 1998;23(1):26-35.
75. Macdonald GA, Greenson JK, Saito K, Cherian SP, Appelman HD, Boland CR. Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis. Hepatology 1998;28(1):90-97. (Pubitemid 28299990)
76. Sicklick JK, Li YX, Melhem A, et al. Hedge-hog signaling maintains resident hepatic progenitors throughout life. Am J Physiol Gastrointest Liver Physiol 2006;290(5):G859-G870.
77. Kaposi-Novak P, Lee JS, Gòmez-Quiroz L, Coulouarn C, Factor VM, Thorgeirsson SS. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype. J Clin Invest 2006;116(6):1582-1595.
78. Shachaf CM, Kopelman AM, Arvanitis C, et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 2004;431(7012):1112-1117. (Pubitemid 39472236)
79. Bartosch B, Thimme R, Blum HE, Zoulim F. Hepatitis C virus-induced hepatocarcinogenesis. J Hepatol 2009;51(4):810-820.
80. Thompson MD, Monga SP. WNT/beta-catenin signaling in liver health and disease. Hepatology 2007;45(5):1298-1305. (Pubitemid 46775794)
81. Tan X, Behari J, Cieply B, Michalopoulos GK, Monga SP. Conditional deletion of beta-catenin reveals its role in liver growth and regeneration. Gastroenterology 2006;131(5):1561-1572. (Pubitemid 44708943)
82. Benhamouche S, Decaens T, Perret C, Colnot S. Wnt/beta-catenin pathway and liver metabolic zonation: a new player for an old concept [in French]. Med Sci (Paris) 2006;22(11):904-906.
83. Cieply B, Zeng G, Proverbs-Singh T, Geller DA, Monga SP. Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin gene. Hepatology 2009;49(3):821-831.
84. Laurent-Puig P, Zucman-Rossi J. Genetics of hepatocellular tumors. Oncogene 2006;25(27):3778-3786. (Pubitemid 43980473)
85. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 2002;36(6):1349-1354.
86. Roskams T, Yang SQ, Koteish A, et al. Oxidative stress and oval cell accumulation in mice and humans with alcoholic and non-alcoholic fatty liver disease. Am J Pathol 2003;163(4):1301-1311. (Pubitemid 37175079)
87. Hu W, Feng Z, Eveleigh J, et al. The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. Carcinogenesis 2002;23(11):1781-1789. (Pubitemid 35355927)
88. Bruix J, Sherman M;Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005;42(5):1208-1236.
89. Farinati F, Marino D, De Giorgio M, et al. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol 2006;101(3):524-532. (Pubitemid 43340928)
90. Liu XE, Desmyter L, Gao CF, et al. Nglycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus. Hepatology 2007;46(5):1426-1435. (Pubitemid 350155524)
91. Capurro M, Wanless IR, Sherman M, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 2003;125(1):89-97. (Pubitemid 36799110)
92. Marrero JA, Romano PR, Nikolaeva O, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005;43(6):1007-1012. (Pubitemid 41627986)
93. Tateishi R, Shiina S, Yoshida H, et al. Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology 2006;44(6):1518-1527. (Pubitemid 44953657)
94. Fujiyama S, Tanaka M, Maeda S, Ashihara H, Hirata R, Tomita K. Tumor markers in early diagnosis, follow-up and management of patients with hepatocellular carcinoma. Oncology 2002;62(suppl 1):57-63. (Pubitemid 34702021)
95. Colli A, Fraquelli M, Casazza G, et al. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 2006;101(3):513-523. (Pubitemid 43340927)
96. Kim SH, Kim SH, Lee J, et al. Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am J Roentgenol 2009;192(6):1675-1681.
97. Lee JY, Kim SH, Jeon YH, et al. Ferucarbotran-enhanced magnetic resonance imaging versus gadoxetic acid-enhanced magnetic resonance imaging for the preoperative detection of hepatocellular carcinoma: initial experience. J Comput Assist Tomogr 2010;34(1):127-134.
98. Marin D, Di Martino M, Guerrisi A, et al. Hepatocellular carcinoma in patients with cirrhosis: qualitative comparison of gadobenate dimeglumine-enhanced MR imaging and multiphasic 64-section CT. Radiology 2009;251(1):85-95.
99. Ooi LP, Crawford DH, Gotley DC, et al. Evidence that "myofibroblast- like" cells are the cellular source of capsular collagen in hepatocellular carcinoma. J Hepatol 1997;26(4):798-807. (Pubitemid 27145702)
100. Ng IO, Lai EC, Ng MM, Fan ST. Tumor encapsulation in hepatocellular carcinoma. A pathologic study of 189 cases. Cancer 1992;70(1):45-49.
101. Lim JH, Kim EY, Lee WJ, et al. Regenerative nodules in liver cirrhosis: findings at CT during arterial portography and CT hepatic arteriography with histopathologic correlation. Radiology 1999;210(2):451-458. (Pubitemid 29055315)
102. Willatt JM, Hussain HK, Adusumilli S, Marrero JA. MR Imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies. Radiology 2008;247(2):311-330.
103. Hytiroglou P, Park YN, Krinsky G, Theise ND. Hepatic precancerous lesions and small hepatocellular carcinoma. Gastroenterol Clin North Am 2007;36(4):867-887, vii.
104. Borzio M, Fargion S, Borzio F, et al. Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development. J Hepatol 2003;39(2):208-214. (Pubitemid 36920556)
105. Kudo M. Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol 2009;44(suppl 19):112-118.
106. Kudo M. The 2008 Okuda lecture: Management of hepatocellular carcinoma: from surveillance to molecular targeted therapy. J Gastroenterol Hepatol 2010;25(3):439-452.
107. van Montfoort JE, Stieger B, Meijer DK, Weinmann HJ, Meier PJ, Fattinger KE. Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1. J Pharmacol Exp Ther 1999;290(1):153-157. (Pubitemid 29302315)
108. Pascolo L, Petrovic S, Cupelli F, et al. Abc protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles. Biochem Biophys Res Commun 2001;282(1):60-66. (Pubitemid 32924345)
109. Narita M, Hatano E, Arizono S, et al. Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol 2009;44(7):793-798.
110. Sun HY, Lee JM, Shin CI, et al. Gadoxetic acid-enhanced magnetic resonance imaging for differentiating small hepatocellular carcinomas (< or =2 cm in diameter) from arterial enhancing pseudolesions: special emphasis on hepatobiliary phase imaging. Invest Radiol 2010;45(2):96-103.
111. Huppertz A, Haraida S, Kraus A, et al. Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT - initial observations. Radiology 2005;234(2):468-478. (Pubitemid 40139918)
112. Forner A, Vilana R, Ayuso C, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008;47(1):97-104. (Pubitemid 351171046)
113. Choi D, Mitchell DG, Verma SK, et al. Hepatocellular carcinoma with indeterminate or false-negative findings at initial MR imaging: effect on eligibility for curative treatment initial observations. Radiology 2007;244(3):776-783. (Pubitemid 47292088)
114. Saborido BP, Díaz JC, de Los Galanes SJ, et al. Does preoperative fine needle aspiration-biopsy produce tumor recurrence in patients following liver transplantation for hepatocellular carcinoma? Transplant Proc 2005;37(9):3874-3877.
115. Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008;48(4):1312-1327.
116. Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100(10):698-711.
117. Cance WG, Stewart AK, Menck HR. The National Cancer Data Base Report on treatment patterns for hepatocellular carcinomas: improved survival of surgically resected patients, 1985-1996. Cancer 2000;88(4):912-920.
118. Dufour JF, Johnson P. Liver cancer: from molecular pathogenesis to new therapies: summary of the EASL single topic conference. J Hepatol 2010;52(2):296-304.
119. Suzuki T, Yano H, Nakashima Y, Nakashima O, Kojiro M. Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process. J Gastroenterol Hepatol 2002;17(9):994-1000.
120. Tien LT, Ito M, Nakao M, et al. Expression of beta-catenin in hepatocellular carcinoma. World J Gastroenterol 2005;11(16):2398-2401.
121. Laurent-Puig P, Legoix P, Bluteau O, et al. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 2001;120(7):1763-1773. (Pubitemid 32523494)
122. Ashida K, Kishimoto Y, Nakamoto K, et al. Loss of heterozygosity of the retinoblastoma gene in liver cirrhosis accompanying hepatocellular carcinoma. J Cancer Res Clin Oncol 1997;123(9):489-495. (Pubitemid 27436008)
123. Zhang XL, Shi JQ, Zuo SH. A comparative study of the expression of ras oncogenic protein P21 and oncofetal protein AFP, CEA in human hepatocellular carcinoma (HCC) [in Chinese]. Zhonghua Bing Li Xue Za Zhi 1994;23(3):155-158.
124. Honda K, Sbisà E, Tullo A, et al. p53 mutation is a poor prognostic indicator for survival in patients with hepatocellular carcinoma undergoing surgical tumour ablation. Br J Cancer 1998;77(5):776-782. (Pubitemid 28077466)
125. Hayashi H, Sugio K, Matsumata T, Adachi E, Takenaka K, Sugimachi K. The clinical significance of p53 gene mutation in hepatocellular carcinomas from Japan. Hepatology 1995;22(6):1702-1707.
126. Määttä M, Soini Y, Liakka A, Autio-Harmainen H. Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in hepatocellular and pancreatic adenocarcinoma: implications for tumor progression and clinical prognosis. Clin Cancer Res 2000;6(7):2726-2734.
127. Wang W, Yang LY, Huang GW, et al. Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis. Br J Cancer 2004;90(12):2349-2355. (Pubitemid 38961899)
128. Wang W, Yang LY, Yang ZL, Huang GW, Lu WQ. Expression and significance of RhoC gene in hepatocellular carcinoma. World J Gastroenterol 2003;9(9):1950-1953. (Pubitemid 37168419)
129. Chen JS, Wang Q, Fu XH, et al. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9. Hepatol Res 2009;39(2):177-186.
130. Chiang DY, Villanueva A, Hoshida Y, et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 2008;68(16):6779-6788.
131. Matsui O, Kadoya M, Kameyama T, et al. Benign and malignant nodules in cirrhotic livers: distinction based on blood supply. Radiology 1991;178(2):493-497.
132. Choi BI, Han JK, Hong SH, et al. Dysplastic nodules of the liver: imaging findings. Abdom Imaging 1999;24(3):250-257. (Pubitemid 29215356)
133. Hayashi M, Matsui O, Ueda K, et al. Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium. AJR Am J Roentgenol 1999;172(4):969-976. (Pubitemid 29505622)
134. Vullierme MP, Paradis V, Chirica M, et al. What is new in the management of hepatocellular carcinoma complicating cirrhosis? [in French]. J Chir (Paris) 2009 Jul 28. [Epub ahead of print]
135. Christofori G, Naik P, Hanahan D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature 1994;369(6479):414-418.
136. Mínguez B, Tovar V, Chiang D, Villanueva A, Llovet JM. Pathogenesis of hepatocellular carcinoma and molecular therapies. Curr Opin Gastroenterol 2009;25(3):186-194.
137. Edmondson HA. Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood. AMA J Dis Child 1956;91(2):168-186.
138. Torbenson M. Review of the clinicopathologic features of fibrolamellar carcinoma. Adv Anat Pathol 2007;14(3):217-223. (Pubitemid 46659192)
139. Berman MA, Burnham JA, Sheahan DG. Fibrolamellar carcinoma of the liver: an immunohistochemical study of nineteen cases and a review of the literature. Hum Pathol 1988;19(7):784-794.
140. El-Serag HB, Davila JA. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology 2004;39(3):798-803. (Pubitemid 38337660)
141. Liu S, Chan KW, Wang B, Qiao L. Fibrolamellar hepatocellular carcinoma. Am J Gastroenterol 2009;104(10):2617-2624; quiz 2625.
142. Vivekanandan P, Micchelli ST, Torbenson M. Anterior gradient-2 is overexpressed by fibrolamellar carcinomas. Hum Pathol 2009;40(3):293-299
143. Marchio A, Pineau P, Meddeb M, et al. Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients. Oncogene 2000;19(33):3733-3738. (Pubitemid 30621178)
144. Orsatti G, Hytiroglou P, Thung SN, Ishak KG, Paronetto F. Lamellar fibrosis in the fibrolamellar variant of hepatocellular carcinoma: a role for transforming growth factor beta. Liver 1997;17(3):152-156. (Pubitemid 27363867)
145. Li W, Tan D, Zenali MJ, Brown RE. Constitutive activation of nuclear factor-kappa B (NF-kB) signaling pathway in fibrolamellar hepatocellular carcinoma. Int J Clin Exp Pathol 2010;3(3):238-243.
146. Zenali MJ, Tan D, Li W, Dhingra S, Brown RE. Stemness characteristics of fibrolamellar hepatocellular carcinoma: immunohistochemical analysis with comparisons to conventional hepatocellular carcinoma. Ann Clin Lab Sci 2010;40(2):126-134.
147. Ichikawa T, Federle MP, Grazioli L, Madariaga J, Nalesnik M, Marsh W. Fibrolamellar hepatocellular carcinoma: imaging and pathologic findings in 31 recent cases. Radiology 1999;213(2):352-361. (Pubitemid 29510577)
148. Craig JR, Peters RL, Edmondson HA, Omata M. Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features. Cancer 1980;46(2):372-379. (Pubitemid 10085954)
149. Stevens WR, Johnson CD, Stephens DH, Nagorney DM. Fibrolamellar hepatocellular carcinoma: stage at presentation and results of aggressive surgical management. AJR Am J Roentgenol 1995;164(5):1153-1158.
150. Stipa F, Yoon SS, Liau KH, et al. Outcome of patients with fibrolamellar hepatocellular carcinoma. Cancer 2006;106(6):1331-1338. (Pubitemid 43363911)
151. Maniaci V, Davidson BR, Rolles K, et al. Fibrolamellar hepatocellular carcinoma: prolonged survival with multimodality therapy. Eur J Surg Oncol 2009;35(6):617-621.
152. Sirivatanauksorn Y, Sirivatanauksorn V, Lemoine NR, Williamson RC, Davidson BR. Genomic homogeneity in fibrolamellar carcinomas. Gut 2001;49(1):82-86. (Pubitemid 32601883)
153. Pinna AD, Iwatsuki S, Lee RG, et al. Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation. Hepatology 1997;26(4):877-883. (Pubitemid 27413652)
154. Sirivatanauksorn Y, Sirivatanauksorn V, Bhattacharya S, et al. Genomic heterogeneity in synchronous hepatocellular carcinomas. Gut 1999;45(5):761-765. (Pubitemid 29492154)
155. Kakar S, Burgart LJ, Batts KP, Garcia J, Jain D, Ferrell LD. Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis. Mod Pathol 2005;18(11):1417-1423. (Pubitemid 41509395)