Digestive Diseases

Review Article

Pathology and Pathogenesis of Hepatocellular Carcinoma

Röcken C. · Carl-McGrath S.

Author affiliations

Department of Pathology, Otto-von-Guericke-University of Magdeburg, Germany

Related Articles for ""

Dig Dis 2001;19:269–278

Log in to MyKarger to check if you already have access to this content.


Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!


If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.

Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select
* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Review Article

Published online: March 27, 2002
Issue release date: 2001

Number of Print Pages: 10
Number of Figures: 2
Number of Tables: 3

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and among the most common cancers worldwide. The distribution pattern of HCC shows geographical variation and its pathogenesis is multifactorial. Environmental, infectious, nutritional, metabolic, and endocrine factors contribute directly or indirectly to hepatocarcinogenesis. The synchronous occurrence of different risk factors, such as chronic viral hepatitis B and C, aflatoxin exposure, alcohol consumption or iron overload, in a single patient or patient population further increases the risk. HCC is commonly associated with chronic hepatitis and liver cirrhosis. Different genes have been implicated in the pathogenesis of HCC, and may be divided into four major groups: genes regulating DNA damage response; genes involved in cell cycle control; genes involved in growth inhibition and apoptosis, and genes responsible for cell–cell interaction and signal transduction. Hepatocarcinogenesis is mediated by loss of heterozygosity, somatic mutation, de novo methylation, and/or functional inactivation. As yet, there is no evidence for an ordered sequence of genomic events leading to hepatocarcinogenesis. The pattern of genomic alterations shows great variability, often between two different HCCs from a single patient. HCC evolves from precancerous lesions, and well-differentiated HCC further progresses to a less differentiated form. However, there is still great need for the definition of objective morphological, phenotypic and genetic markers for the progression of HCC.

© 2002 S. Karger AG, Basel




Related Articles:


References

  1. Hamilton SR, Aaltonen LA (eds): Pathology and Genetics of Tumours of the Digestive System. Lyon, IARC Press, 2000.
  2. Anthony PP: Hepatocellular carcinoma: An overview. Histopathology 2001;39:109–118.
    External Resources
  3. Tannapfel A, Benicke M, Markwarth A, Katalanic A, Wittekind Ch: Multicentric or metastatic origin of hepatocellular carcinoma. Pathol Res Pract 2001;197:314.
  4. Shimada M, Hamatsu T, Yamashita Y, Rikimaru T, Taguchi K, Utsunomiya T, Shirabe K, Sugimachi K: Characteristics of multicentric hepatocellular carcinomas: Comparison with intrahepatic metastasis. World J Surg 2001;25:991–995.
    External Resources
  5. Ariizumi S, Takasaki K, Yamamoto M, Ohtsubo T, Saito A, Nakano M: Multicentric hepatocellular carcinomas tend to grow in more damaged segments of the liver. J Gastroenterol 2000;35:441–444.
    External Resources
  6. Kojiro M: Pathology of hepatocellular carcinoma; in Okuda K, Tabor E (eds): Liver Cancer. New York, Churchill Livingstone, 1997, pp 165–187.
  7. Ishak KG, Goodman ZD, Stocker JT: Tumors of the liver and intrahepatic bile ducts. Washington, Armed Forces Institute of Pathology, 2001.
  8. D’Errico A, Baccarini P, Fiorentino M, Ceccarelli C, Bonazzi C, Ponzetto A, Scoazec JY, Mancini AM, Grigioni WF: Histogenesis of primary liver carcinomas: Strengths and weaknesses of cytokeratin profile and albumin mRNA detection. Hum Pathol 1996;27:599–604.
  9. Hurlimann J, Gardiol D: Immunohistochemistry in the differential diagnosis of liver carcinomas. Am J Surg Pathol 1991;15:280–288.
  10. Ma CK, Zarbo RJ, Frierson HF Jr, Lee MW: Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. Am J Clin Pathol 1993;99:551–557.
  11. Minervini MI, Demetris AJ, Lee RG, Carr BI, Madariaga J, Nalesnik MA: Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors. Mod Pathol 1997;10:686–692.
  12. Oliveira AM, Erickson LA, Burgart LJ, Lloyd RV: Differentiation of primary and metastatic clear cell tumors in the liver by in situ hybridization for albumin messenger RNA. Am J Surg Pathol 2000;24:177–182.
  13. Borscheri N, Roessner A, Röcken C: Canalicular immunostaining of Neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas. Am J Surg Pathol 2001;25:1297–1303.
  14. International Working Party: Terminology of nodular hepatocellular lesions. Hepatology 1995;22:983–993.
  15. Hytiroglou P, Theise ND: Differential diagnosis of hepatocellular nodular lesions. Semin Diagn Pathol 1998;15:285–299.
  16. Lee RG, Tsamandas AC, Demetris AJ: Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: Matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology 1997;26:1415–1422.
  17. Borzio M, Bruno S, Roncalli M, Mels GC, Ramella G, Borzio F, Leandro G, Servida E, Podda M: Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: A prospective study. Gastroenterology 1995;108:812–817.
  18. Ganne-Carrie N, Chastang C, Chapel F, Munz C, Pateron D, Sibony M, Deny P, Trinchet JC, 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. Hepatology 1996;23:1112–1118.
  19. Kondo Y: Pathology of early hepatocellular carcinoma and preneoplastic lesions in the liver; in Okuda K, Tabor E (eds): Liver Cancer. New York, Churchill Livingstone, 1997, pp 135–154.
  20. Le Bail B, Bernard PH, Carles J, Balabaud C, Bioulac-Sage P: Prevalence of liver cell dysplasia and association with HCC in a series of 100 cirrhotic liver explants. J Hepatol 1997;27:835–842.
  21. Ueno Y, Moriyama M, Uchida T, Arakawa Y: Irregular regeneration of hepatocytes is an important factor in the hepatocarcinogenesis of liver disease. Hepatology 2001;33:357–362.
  22. Bralet MP, Regimbeau JM, Pineau P, Dubois S, Loas G, Degos F, Valla D, Belghiti J, Degott C, Terris B: Hepatocellular carcinoma occurring in nonfibrotic liver: Epidemiologic and histopathologic analysis of 80 French cases. Hepatology 2000;32:200–204.
  23. Grando-Lemaire V, Guettier C, Chevret S, Beaugrand M, Trinchet JC: Hepatocellular carcinoma without cirrhosis in the West: Epidemiological factors and histopathology of the non-tumorous liver. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. J Hepatol 1999;31:508–513.
  24. Colombo M: Hepatitis C virus and hepatocellular carcinoma. Semin Liver Dis 1999;19:263–269.
  25. Ray RB, Ray R: Hepatitis C virus core protein: Intriguing properties and functional relevance. FEMS Microbiol Lett 2001;202:149–156.
  26. Shimotohno K: Hepatitis C virus and its pathogenesis. Semin Cancer Biol 2000;10:233–240.
    External Resources
  27. Bannasch P, Zerban H: Experimental chemical hepatocarcinogenesis; in Okuda K, Tabor E (eds): Liver Cancer. New York, Churchill Livingstone, 1997, pp 213–253.
  28. Wogan GN: Impacts of chemicals on liver cancer risk. Semin Cancer Biol 2000;10:201–210.
    External Resources
  29. Zhou H, Ortiz-Pallardo ME, Ko Y, Fischer HP: Is heterozygous alpha-1-antitrypsin deficiency type PIZ a risk factor for primary liver carcinoma? Cancer 2000;88:2668–2676.
  30. Fracanzani AL, Conte D, Fraquelli M, Taioli E, Mattioli M, Losco A, Fargion S: Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology 2001;33:647–651.
  31. Deugnier Y, Turlin B: Iron and hepatocellular carcinoma. J Gastroenterol Hepatol 2001;16:491–494.
    External Resources
  32. Ozturk M: Genetic aspects of hepatocellular carcinogenesis. Semin Liver Dis 1999;19:235–242.
  33. Sobin LH, Wittekind Ch (eds): TNM Classification of Malignant Tumours, ed 5. New York, Wiley, 1997.
  34. Hamada K, Koyama T, Shimizu K, Ikawa S, Kawate S, Yokota J, Ohwada S, Morishita Y: Absence of p51 mutation in human hepatocellular carcinoma. Cancer Lett 2000;148:161–164.
    External Resources
  35. Mihara M, Nimura Y, Ichimiya S, Sakiyama S, Kajikawa S, Adachi W, Amano J, Nakagawara A: Absence of mutation of the p73 gene localized at chromosome 1p36.3 in hepatocellular carcinoma. Br J Cancer 1999;79:164–167.
  36. Peng CY, Tsai SL, Yeh CT, Hung SP, Chen MF, Chen TC, Chu CM, Liaw YF: Genetic alternations of p73 are infrequent but may occur in early stage hepatocellular carcinoma. Anticancer Res 2000;20:1487–1492.
  37. Kawate S, Ohwada S, Hamada K, Koyama T, Takenoshita S, Morishita Y, Hagiwara K: Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma. Int J Mol Med 2001;8:49–52.
    External Resources
  38. Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y: AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nature Genet 2000;24:245–250.
  39. Park WS, Dong SM, Kim SY, Na EY, Shin MS, Pi JH, Kim BJ, Bae JH, Hong YK, Lee KS, Lee SH, Yoo NJ, Jang JJ, Pack S, Zhuang Z, Schmidt L, Zbar B, Lee JY: Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res 1999;59:307–310.
    External Resources
  40. Yano M, Asahara T, Dohi K, Mizuno T, Iwamoto KS, Seyama T: Close correlation between a p53 or hMSH2 gene mutation in the tumor and survival of hepatocellular carcinoma patients. Int J Oncol 1999;14:447–451.
    External Resources
  41. Jihua C, Xisheng L, Shengli C, Zongxian C, Guang C, Ruyu D: Detection of point mutations of BCL10 gene in hepatocellular carcinoma tissues: Report of 46 cases. Hum Mutat 2000;15:482–483.
    External Resources
  42. Fujiwara Y, Hoon DS, Yamada T, Umeshita K, Gotoh M, Sakon M, Nishisho I, Monden M: PTEN/MMAC1 mutation and frequent loss of heterozygosity identified in chromosome 10q in a subset of hepatocellular carcinomas. Jpn J Cancer Res 2000;91:287–292.
  43. Yao YJ, Ping XL, Zhang H, Chen FF, Lee PK, Ahsan H, Chen CJ, Lee PH, Peacocke M, Santella RM, Tsou HC: PTEN/MMAC1 mutations in hepatocellular carcinomas. Oncogene 1999;18:3181–3185.
    External Resources
  44. Lin KH, Shieh HY, Chen SL, Hsu HC: Expression of mutant thyroid hormone nuclear receptors in human hepatocellular carcinoma cells. Mol Carcinog 1999;26:53–61.

Article / Publication Details

First-Page Preview
Abstract of Review Article

Published online: March 27, 2002
Issue release date: 2001

Number of Print Pages: 10
Number of Figures: 2
Number of Tables: 3

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
TOP