User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Preneoplastic lesions in human hepatocarcinogenesis

Primary tabs

Libbrecht, Louis [UCL] Desmet, Valeer Roskams, Tania

The early stages of hepatocarcinogenesis in human chronic liver diseases are characterized by the emergence of preneoplastic lesions of which some will eventually develop into hepatocellular carcinoma (HCC). Basic studies on the genetic and epigenetic alterations of these preneoplastic lesions may eventually lead to new therapeutic strategies. Clinicopathological studies are also important in order to determine optimal management of patients with a preneoplastic lesion. This article aims to provide a comprehensive review of the current concepts of preneoplastic lesion in chronic liver diseases. The microscopical small-cell dysplastic focus is the smallest morphologically recognizable precursor lesion of HCC and therefore is a logical target of study to elucidate the earliest events in hepatocarcinogenesis. In contrast, large-cell dysplasia is not a precursor lesion, but appears to be of clinical value because of its good predictive value for development of HCC. Dysplastic nodules (DNs) are macroscopically recognizable precursor lesions of HCC and high-grade DNs (HGDNs) have a risk of malignant transformation. Detection of DNs and correct differentiation from small HCC (<2 cm) is sometimes difficult, especially when only imaging techniques are used. Additional clinicopathological studies on identification and optimal treatment of DNs are necessary. Molecular studies on HGDNs and small HCCs may yield much information on the genetic mechanisms involved in the transition from severe dysplasia to early malignancy. In contrast, currently available data indicate that (large) regenerative nodules do not represent a distinct step in hepatocarcinogenesis. Animal models will be helpful in the further unravelling of human HCC development, provided that studies are performed on models that are good representatives of human hepatocarcinogenesis. We propose three criteria by which good mimickers can be identified.

Document type Article de périodique (Journal article) – Synthèse de littérature
Access type Accès restreint
Publication date 2005
Language Anglais
Journal information "Liver International" - Vol. 25, no.1, p. 16-27 (2005)
Peer reviewed yes
Publisher Wiley-Blackwell Publishing, Inc. ((United States) Malden, MA)
issn 1478-3223
e-issn 1478-3231
Publication status Publié
Affiliation [KUL]
MESH Subject Animals ; Carcinoma, Hepatocellular ; Cell Proliferation ; Disease Models, Animal ; Hepatocytes ; Humans ; Liver Neoplasms ; Precancerous Conditions
Links
  1. Llovet Josep M, Burroughs Andrew, Bruix Jordi, Hepatocellular carcinoma, 10.1016/s0140-6736(03)14964-1
  2. Russo Mark W., Wei Jeffrey T., Thiny Michelle T., Gangarosa Lisa M., Brown Alphonso, Ringel Yehuda, Shaheen Nicholas J., Sandler Robert S., Digestive and liver diseases statistics, 2004, 10.1053/j.gastro.2004.01.025
  3. Yeh Shiou–Hwei, Chen Pei–Jer, Shau Wen–Yi, Chen Ya–Wen, Lee Po–Huang, Chen Jung–Ta, Chen Ding–Shinn, Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma, 10.1053/gast.2001.27211
  4. Inoue H, Seitz H K, Viruses and alcohol in the pathogenesis of primary hepatic carcinoma : , 10.1097/00008469-200102000-00016
  5. Macarthur M., Inflammation and Cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy, 10.1152/ajpgi.00475.2003
  6. Laurent–Puig Pierre, Legoix Patricia, Bluteau Olivier, Belghiti Jacques, Franco Dominique, Binot Frederic, Monges Geneviève, Thomas Gilles, Bioulac–Sage Paulette, Zucman–Rossi Jessica, Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis, 10.1053/gast.2001.24798
  7. Feitelson Mark A, Sun Bill, Lale Satiroglu Tufan N, Liu Jie, Pan Jingbo, Lian Zhaorui, Genetic mechanisms of hepatocarcinogenesis, 10.1038/sj.onc.1205434
  8. Pitot Henry C, Pathways of progression in hepatocarcinogenesis, 10.1016/s0140-6736(01)06038-x
  9. Chen Xin, Cheung Siu Tim, So Samuel, Fan Sheung Tat, Barry Christopher, Higgins John, Lai Kin-Man, Ji Jiafu, Dudoit Sandrine, Ng Irene O.L., van de Rijn Matt, Botstein David, Brown Patrick O., Gene Expression Patterns in Human Liver Cancers, 10.1091/mbc.02-02-0023
  10. Saeki Rieko, Nagai Hisaki, Kaneko Shuichi, Unoura Masashi, Yamanaka Naoki, Okamoto Eiso, Kobayashi Kenichi, Matsubara Kenichi, Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning, 10.1016/s0168-8278(00)80165-8
  11. Su, phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia, 431, 391 (1997)
  12. Borzio Mauro, Roncalli Massimo, Treré Davide, Derenzini Massimo, Preneoplastic cellular changes in liver : Preneoplastic Cellular Changes in Liver, 10.1002/hep.510280538
  13. Libbrecht L, Craninx M, Nevens F, Desmet V, Roskams T, Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis, 10.1046/j.1365-2559.2001.01172.x
  14. Thorgeirsson Snorri S., Grisham Joe W., Molecular pathogenesis of human hepatocellular carcinoma, 10.1038/ng0802-339
  15. Borzio Mauro, Fargion Silvia, Borzio Franco, Fracanzani Anna Ludovica, Croce Anna Maria, Stroffolini Tommaso, Oldani Silvia, Cotichini Rodolfo, Roncalli Massimo, Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development, 10.1016/s0168-8278(03)00190-9
  16. Watanabe S., Okita K., Harada T., Kodama T., Numa Y., Takemoto T., Takahashi T., Morphologic studies of the liver cell dysplasia, 10.1002/1097-0142(19830615)51:12<2197::aid-cncr2820511208>3.0.co;2-5
  17. Anthony, a premalignant condition, 26, 217 (1973)
  18. Le Bail Brigitte, Bernard Pierre-Henri, Carles Jacques, Balabaud Charles, Bioulac-Sage Paulette, Prevalence of liver cell dysplasia and association with HCC in a series of 100 cirrhotic liver explants, 10.1016/s0168-8278(97)80321-2
  19. Blanc Jean Frédéric, Ledinghen Victor De, Trimoulet Pascale, Bail Brigitte Le, Bernard Pierre-Henri, Saric Jean, Balabaud Charles, Bioulac-Sage Paulette, Premalignant lesions and hepatocellular carcinoma in a non-cirrhotic alcoholic patient with iron overload and normal transferrin saturation, 10.1016/s0168-8278(99)80080-4
  20. Marchio A, Chromosomal abnormalities in liver cell dysplasia detected by comparative genomic hybridisation, 10.1136/mp.54.4.270
  21. Libbrecht, correlation with putative progenitor cells, 33, 76 (2000)
  22. Libbrecht Louis, De Vos Rita, Cassiman David, Desmet Valeer, Aerts Raymond, Roskams Tania, Hepatic Progenitor Cells in Hepatocellular Adenomas : , 10.1097/00000478-200111000-00006
  23. Dumble, oval cells give rise to hepatocellular carcinoma, 23, 435 (2002)
  24. Libbrecht Louis, Roskams Tania, Hepatic progenitor cells in human liver diseases, 10.1016/s1084952102001258
  25. Roncalli M., Borzio M., Brando B., Colloredo G., Servida E., Abnormal DNA content in liver-cell dysplasia: A flow cytometric study, 10.1002/ijc.2910440203
  26. Thomas, a DNA aneuploid lesion with distinct morphologic features, 23, 496 (1992)
  27. Lee, matched case-control study, pathological analysis, and pathogenetic hypothesis, 26, 1415 (1997)
  28. Santoni-Rugiu, Am J Pathol, 149, 407 (1996)
  29. Libbrecht, European J Cancer Prevent, 9, 444 (2000)
  30. Ferrell, cirrhosis, hepatitis, and primary liver tumors. update and diagnostic problems, 13, 679 (2000)
  31. Borzio Mauro, Bruno Savino, Roncalli Massimo, Colloredo Mels Guido, Ramella Giorgio, Borzio Franco, Leandro Gioacchino, Servida Ernesto, Podda Mauro, Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: A prospective study, 10.1016/0016-5085(95)90455-7
  32. Ganne-Carrie N, Chastang C, Chapel F, Munz C, Pateron D, Sibony M, Deny P, Trinchet J, Callard P, Guettier C, Beaugrand M, Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis, 10.1002/hep.510230527
  33. Degos, time to occurrence of hepatocellular carcinoma and death, 47, 131 (2000)
  34. Donato M, High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity, 10.1053/jhep.2001.26820
  35. Eguchi Akira, Nakashima Osamu, Okudaira Sadayuki, Sugihara Shigetaka, Kojiro Masamichi, Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma, 10.1002/hep.1840150516
  36. Kaji, Am J Gastroenterol, 89, 903 (1994)
  37. Arakawa Masahiro, Kage Masayoshi, Sugihara Shigetaka, Nakashima Toshiro, Suenaga Masahiro, Okuda Kunio, Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver, 10.1016/0016-5085(86)90458-0
  38. Takayama T, Kosuge T, Yamazaki S, Hasegawa H, Okazaki N, Takayasu K, Hirohashi S, Sakamoto M, Makuuchi M, Motoo Y, Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma, 10.1016/0140-6736(90)92768-d
  39. International Working Party., Gastroenterology, 22, 983 (1995)
  40. Maggioni M, Molecular Changes in Hepatocellular Dysplastic Nodules on Microdissected Liver Biopsies, 10.1053/jhep.2000.18425
  41. Sun, loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region, 33, 1415 (2001)
  42. Tornillo, high-grade dysplastic nodules represent early stages of hepatocellular carcinoma, 82, 547 (2002)
  43. Roncalli, implications for diagnosis and classification, 30, 1174 (1999)
  44. Seki, a clinicopathological study, 6, 3469 (2000)
  45. Lencioni Riccardo, Caramella D., Bartolozzi C., Mazzeo S., Coscio G. Di, Percutaneous ethanol injection therapy of adenomatous hyperplastic nodules in cirrhotic liver disease, 10.3109/02841859409172351
  46. Ishikawa, Hepato-Gastroenterology, 49, 1591 (2002)
  47. Burrel, an explant correlation, 38, 1034 (2003)
  48. Krinsky, sensitivity of magnetic resonance imaging, 8, 1156 (2002)
  49. Libbrecht, pathological evaluation and accuracy of pretransplantation imaging examinations, 8, 749 (2002)
  50. De Ledinghen, spiral computed tomography or magnetic resonance imaging? A prospective study of 88 nodules in 34 patients, 14, 159 (2002)
  51. Quaglia A, Tibballs J, Grasso A, Prasad N, Nozza P, Davies S E, Burroughs A K, Watkinson A, Dhillon A P, Focal nodular hyperplasia-like areas in cirrhosis, 10.1046/j.1365-2559.2003.01550.x
  52. Verslype C., Libbrecht L., Nevens F., Bielen D., Vanbeckevoort D., Fevery J., Pirenne J., Roskams T., Relevance of detecting additional small HCC lesions prior to liver transplantation, 10.1016/s0168-8278(03)80569-x
  53. Hayashi Paul H., Trotter James F., Forman Lisa, Kugelmas Marcelo, Steinberg Tracy, Russ Paul, Wachs Michael, Bak Thomas, Kam Igal, Everson Gregory T., Impact of pretransplant diagnosis of hepatocellular carcinoma on cadveric liver allocation in the era of MELD, 10.1002/lt.20020
  54. Llovet, diagnosis, staging, and treatment of hepatocellular carcinoma, 10, 115 (2004)
  55. Huang Guan-Tarn, Sheu Jin-Chuan, Yang Pei-Ming, Lee Hsuan-Shu, Wang Teh-Hong, Chen Ding-Shinn, Ultrasound-guided cutting biopsy for the diagnosis of hepatocellular carcinoma — a study based on 420 patients, 10.1016/s0168-8278(96)80120-6
  56. Quaglia A, Bhattacharjya S, Dhillon A P, Limitations of the histopathogical diagnosis and prognostic assessment of hepatocellular carcinoma, 10.1046/j.1365-2559.2001.01000.x
  57. Roncalli, focus on diagnostic criteria on liver biopsy. A Western experience, 2004, 9 (2004)
  58. Ryder S D, Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults, 10.1136/gut.52.suppl_3.iii1
  59. Bruix Jordi, Sherman Morris, Llovet Josep M, Beaugrand Michel, Lencioni Riccardo, Burroughs Andrew K, Christensen Erik, Pagliaro Luigi, Colombo Massimo, Rodés Juan, Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference, 10.1016/s0168-8278(01)00130-1
  60. Caturelli, the hepatologist's point of view, 10, 26 (2004)
  61. Torzilli, validation and extension of an Eastern approach in a Western community hospital, 10, 30 (2004)
  62. Paradis Valérie, Bièche Ivan, Dargère Delphine, Laurendeau Ingrid, Laurent Christophe, Bioulac Sage Paulette, Degott Claude, Belghiti Jacques, Vidaud Michel, Bedossa Pierre, Molecular Profiling of Hepatocellular Carcinomas (HCC) Using a Large-Scale Real-Time RT-PCR Approach, 10.1016/s0002-9440(10)63700-5
  63. Quaglia A., Dhillon A., Colombari R., Togni R., Dalla Palma P., Michelis F., Bioulac-Sage P., Balabaud C., Winnock M., Burroughs A.K., Dhillon A.P., A novel scoring sytem for the histological diagnosis of hepatocellular carcinoma in cirrhotic liver, 10.1016/s0168-8278(01)81252-6
  64. Hytiroglou Prodromos, Kotoula Vassiliki, Thung Swan N., Tsokos Maria, Fiel M. Isabel, Papadimitriou Constantine S., Telomerase activity in precancerous hepatic nodules, 10.1002/(sici)1097-0142(19980515)82:10<1831::aid-cncr4>3.0.co;2-q
  65. Oh Bong-Kyeong, Jo Chae Kwang, Park Chanil, Kim Kyungsik, Jung Lee Woo, Han Kwang-hyub, Nyun Park Young, Telomere shortening and telomerase reactivation in dysplastic nodules of human hepatocarcinogenesis, 10.1016/s0168-8278(03)00395-7
  66. Millward-Sadler, Pathology of the Liver, 397 (1994)
  67. Aihara Tomohiko, Noguchi Shinzaburo, Sasaki Yo, Nakano Hiroshi, Imaoka Shingi, Clonal analysis of regenerative nodules in hepatitis C virus-induced liver cirrhosis, 10.1016/0016-5085(94)90824-9
  68. Paradis Valerie, Laurendeau Ingrid, Vidaud Michel, Bedossa Pierre, , Clonal analysis of macronodules in cirrhosis, 10.1002/hep.510280409
  69. Diallo Raihanatou, Schaefer Karl-Ludwig, Poremba Christopher, Shivazi Nazli, Willmann Vivian, Buerger Horst, Dockhorn-Dworniczak Barbara, Boecker Werner, Monoclonality in normal epithelium and in hyperplastic and neoplastic lesions of the breast, 10.1002/1096-9896(2000)9999:9999<::aid-path747>3.0.co;2-h
  70. Shiojiri Nobuyoshi, Sano Masayuki, Inujima Sachiko, Nitou Miho, Kanazawa Masaki, Mori Masataka, Quantitative Analysis of Cell Allocation During Liver Development, Using the spfash-Heterozygous Female Mouse, 10.1016/s0002-9440(10)64707-4
  71. Ochiai Toshiya, Urata Yoji, Yamano Takeshi, Yamagishi Hisakazu, Ashihara Tsukasa, Clonal expansion in evolution of chronic hepatitis to hepatocellular carcinoma as seen at an X-chromosome locus, 10.1002/hep.510310311
  72. Tiniakos, a comparative study, 19, 58 (1999)
  73. Anders Robert A., Yerian Lisa M., Tretiakova Maria, Davison Jon M., Quigg Richard J., Domer Peter H., Hoberg Jamie, Hart John, cDNA Microarray Analysis of Macroregenerative and Dysplastic Nodules in End-Stage Hepatitis C Virus-Induced Cirrhosis, 10.1016/s0002-9440(10)63893-x
  74. Colombat Magali, Paradis Valérie, Bièche Ivan, Dargère Delphine, Laurendeau Ingrid, Belghiti Jacques, Vidaud Michel, Degott Claude, Bedossa Pierre, Quantitative RT-PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesis : Gene expression in cirrhotic nodules, 10.1002/path.1451
  75. Roncalli, correlations with hepatocellular carcinoma development during follow-up, 31, 846 (2000)
  76. Hirota, Hepato-Gastroenterology, 29, 49 (1982)
  77. Deugnier, Hepatology, 18, 1363 (1993)
  78. Libbrecht Louis, Meerman Leo, Kuipers Folkert, Roskams Tania, Desmet Valeer, Jansen Peter, Liver pathology and hepatocarcinogenesis in a long-term mouse model of erythropoietic protoporphyria, 10.1002/path.1257
  79. Guyader Dominique, Gandon Yves, Sapey Thierry, Turlin Bruno, Mendler Michel H., Brissot Pierre, Deugnier Yves, Magnetic resonance iron-free nodules in genetic hemochromatosis, 10.1111/j.1572-0241.1999.932_c.x
  80. Krinsky, no increased frequency of dysplastic nodules and hepatocellular carcinoma, 218, 47 (2001)
  81. Lefkowitch Jay H, Yee Herman T, Sweeting Joseph, Green Peter H.R, Magun Arthur M, Iron-rich foci in chronic viral hepatitis, 10.1016/s0046-8177(98)90219-2
  82. Morphological Changes of Early Human Hepatocarcinogenesis, 10.1055/s-2004-823097
  83. Krinsky, regenerative or dysplastic?, 24, 773 (2000)
  84. Terada Tadashi, Kadoya Masumi, Nakanuma Yasuni, Matsui Osamu, Iron-accumulating adenomatous hyperplastic nodule with malignant foci in the cirrhotic liver histopathologic, quantitative iron, and magnetic resonance imaging in vitro studies, 10.1002/1097-0142(19900501)65:9<1994::aid-cncr2820650919>3.0.co;2-b
  85. Shuto, Hepato-Gastroenterology, 46, 2439 (1999)
  86. Kato Kazuki, Ozaki Daisuke, Zheng Kefei, Kondo Fukuo, Urashima Tetsuro, Asano Takehide, Ochiai Takenori, Suzuki Yoshio, Ebara Masaaki, Saisho Hiromitsu, Kondo Yoichiro, Characterization of hyperplastic foci observed in surgical specimens of hepatocellular carcinoma, 10.1046/j.1440-1827.2001.01149.x
  87. Shibata Minoru, Morizane Toshio, Uchida Toshikazu, Yamagami Tomoyuki, Onozuka Yasushi, Nakano Masayuki, Mitamura Keiji, Ueno Yukihisa, Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in chronic hepatitis and cirrhosis with hepatitis-C-virus infection, 10.1016/s0140-6736(97)08002-1
  88. Bannasch, preneoplastic phenotypes mimic responses to insulin and thyroid hormone, 29, 303 (1997)
  89. Lefkowitch Jay H., Arborgh Bengt Å. M., Scheuer Peter J., Oxyphilic Granular Hepatocytes: Mitochondrion-rich Liver Cells in Hepatic Disease, 10.1093/ajcp/74.4.432
  90. Dombrowski, Am J Pathol, 150, 1071 (1997)
  91. Chang, Pathol Annu, 27, 263 (1992)
  92. Muller-Hocker J, Aust D, Rohrbach H, Napiwotzky J, Reith A, Link T A, Seibel P, Holzel D, Kadenbach B, Defects of the respiratory chain in the normal human liver and in cirrhosis during aging, 10.1002/hep.510260324
  93. Mandel, ultrastructural changes in liver biopsies, 34, 776 (2001)
  94. Tanji Kurenai, Bhagat Govind, Vu Tuan H, Monzon Lailani, Bonilla Eduardo, Lefkowitch Jay H, Mitochondrial DNA dysfunction in oncocytic hepatocytes, 10.1034/j.1478-3231.2003.00864.x
  95. Klotz Luisa, Hacker Hans Jörg, Klingmüller Dietrich, Bannasch Peter, Pfeifer Ulrich, Dombrowski Frank, Hepatocellular Alterations after Intraportal Transplantation of Ovarian Tissue in Ovariectomized Rats, 10.1016/s0002-9440(10)65033-x
  96. Sola J., Pardo-Mindán F. J., Zozaya J., Quiroga J., Sangro B., Prieto J., Liver changes in patients with hyperthyroidism, 10.1111/j.1600-0676.1991.tb00516.x
  97. Bayraktar, Hepato-Gastroenterology, 44, 1614 (1997)
  98. Grisham, implications for cancer risk assessment, 18, 59 (1997)
  99. Factor V. M., Laskowska D., Jensen M. R., Woitach J. T., Popescu N. C., Thorgeirsson S. S., Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model, 10.1073/pnas.040428797
  100. Murata M, Accumulation of β-catenin in the cytoplasm and the nuclei during the early hepatic tumorigenesis, 10.1016/s1386-6346(01)00116-4
  101. Harada Naomoto, Oshima Hiroko, Katoh Masahiro, Tamai Yositaka, Oshima Masanobu, Taketo Makoto M., Hepatocarcinogenesis in Mice with β-Catenin and Ha-Ras Gene Mutations, 10.1158/0008-5472.can-03-2123
  102. Calvisi Diego F., Factor Valentina M., Ladu Sara, Conner Elizabeth A., Thorgeirsson Snorri S., Disruption of β-catenin pathway or genomic instability define two distinct categories of liver cancer in transgenic mice, 10.1053/j.gastro.2004.02.014
Bibliographic reference Libbrecht, Louis ; Desmet, Valeer ; Roskams, Tania. Preneoplastic lesions in human hepatocarcinogenesis. In: Liver International, Vol. 25, no.1, p. 16-27 (2005)
Permanent URL http://hdl.handle.net/2078/187263