Surgery Today

, Volume 27, Issue 6, pp 483–490 | Cite as

Cellular DNA content and histopathological analysis in hepatocellular carcinoma with multiple nodules

  • Nobutaka Ichikawa
  • Jiro Fujimoto
  • Eizo Okamoto
  • Naoki Yamanaka
  • Takashi Nishigami


Multiple tumors within the liver are a characteristic feature of hepatocellular carcinoma (HCC). This study investigated alterations in the histologic type and DNA content of multiple nodules of HCC. Both a pathologic examination and flow cytometric DNA analysis were performed on 49 resected specimens of multinodular HCC. The results showed that 35 cases had multiple metastatic satellite nodules around the main tumor (group 1), while 14 had two solitary nodules in different segments without satellite nodules (group 2). In group 1, 28 out of 35 (80.0%) showed a single DNA index while 7 (20.0%) revealed two different DNA contents in the main tumor. The histological type, cytological grade, and DNA index were equivalent between the main and satellite tumors in 100%, 88.6%, and 97.1% of the cases, respectively. In group 2, all tumors showed a single histological type, cytological grade, and DNA index in each nodule. The histological type was identical in 85.7% of the pairs of nodules, but the cytological grade and DNA index were different in 42.9% and 85.7%, respectively. The patients in group 2 showed a significantly higher 5-year survival rate than that in group I (64.8%vs 27.2%,P<0.05). This study thus indicates that the cytological grade and DNA content are useful in distinguishing multicentric occurrence from intrahepatic metastasis in HCC.

Key Words

hepatocellular carcinoma DNA ploidy multiple nodules 


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  1. 1.
    World Health Organization scientific group on prevention and control of hepatocellular carcinoma (1983) Prevention of primary liver cancer: Report on a meeting of a WHO scientific group. Lancet 1:463–465Google Scholar
  2. 2.
    Chiu JH, Kao HW, Wu LH, Chang HM, Lui WY (1983) Prediction of relapse or survival after resection in human hepatomas by DNA flow cytometry. J Clin Invest 89:539–545Google Scholar
  3. 3.
    Okada S, Shimada K, Yamamoto J, Takayama T, Kosuge T, Yamasaki S, Sakamoto M, Hirohashi S (1994) Predictive factors for postoperative recurrence of hepatocellular carcinoma. Gastroenterology 106:1618–1624PubMedGoogle Scholar
  4. 4.
    Fujimoto J, Okamoto E, Yamanaka N, Toyosaka A, Mitsunobu M (1991) Flow cytometric DNA analysis of hepatocellular carcinoma. Cancer 67:939–944PubMedGoogle Scholar
  5. 5.
    Okuda K, Ohtsuki T, Obata H (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56:918–928PubMedGoogle Scholar
  6. 6.
    Castells A, Bruix J, Bru C, Fuster J, Vilana R, Navasa R, Ayuso M, Boix L, Visa J, Rodes J (1993) Treatment of small hepatocellular carcinoma in cirrhotic patients: a cohort study comparing surgical resection and percutaneus ethanol injection. Hepatology 18:1121–1126CrossRefPubMedGoogle Scholar
  7. 7.
    Hartwell LH, Kastan MB (1994) Cell cycle control and cancer. Science 266:1821–1828PubMedGoogle Scholar
  8. 8.
    Look AT, Melvin SL, Williams DL, Brodeur GH, Kalwinsky GV, Murphy SB, Mauer AM (1982) Aneuploidy and percentage of s-phase cells determined by flow cytometry correrate with cell phenotype in childhood acute leukemia. Blood 60:959–967PubMedGoogle Scholar
  9. 9.
    Healey JE, Schroy PC (1953) Anatomy of the biliary ducts within the human liver. Arch Surg 66:599–616Google Scholar
  10. 10.
    Liver Cancer Study Group in Japan (1992) The general rules for the clinical and pathological study of primary liver cancer. 3rd edn. Kanehara, Tokyo, pp 26–35Google Scholar
  11. 11.
    Gibson JB, Sobin LH (1978) Histological typing of tumors of the liver, biliary tract and pancreas (International histological classification of tumors, no 20). World Health Organization, GenevaGoogle Scholar
  12. 12.
    Hedley DW, Friendlander ML, Taylor IW, Ruga CA, Musgrove EA (1984) DNA flow cytometry of paraffin-embedded tissue. Cytometry 5:660CrossRefPubMedGoogle Scholar
  13. 13.
    Vindelov LL, Christensen IJ, Nissen NI (1983) A detergenttripsin method for preparation of nuclei for flow cytometric DNA analysis. Cytometry 3:232–237Google Scholar
  14. 14.
    Hiddemann W, Schmann J, Andreef M (1984) Convention of nomenclature for DNA cytometry. Cytometry 5:445–446CrossRefGoogle Scholar
  15. 15.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481Google Scholar
  16. 16.
    Esteban JM, Shaibani K, Owens M, Joyce J, Bailey A, Battifora H (1991) Effects of fixatives and fixation conditions on DNA ploidy analysis. A need for strict internal DNA standards. Am J Clin Pathol 95:460–466PubMedGoogle Scholar
  17. 17.
    Fidler IJ (1990) Critical factors in the biology of human cancer metastasis: Twenty-eighth G.H.A. Clowes Memorial Award Lecture. Cancer Res 50:6130–6138PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Nobutaka Ichikawa
    • 1
  • Jiro Fujimoto
    • 1
  • Eizo Okamoto
    • 1
  • Naoki Yamanaka
    • 1
  • Takashi Nishigami
    • 2
  1. 1.First Department of SurgeryHyogo College of MedicineNishinomiyaJapan
  2. 2.Second Department of PathologyHyogo College of MedicineNishinomiyaJapan

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