Clinical relevance of DNA-ploidy for liver transplantation due to hepatocellular carcinoma
General-, Laboratory of Clinical Cytology and DNA-cytometry, Visceral- and Transplantation Surgery, Charité, Campus Virchow-Klinikum, Germany
Introduction: The histomorphological classification of hepatocellular carcinoma (HCC) is difficult, mainly because there is no valid grading system so far, providing reliable and reproducible results. According to previous study, liver transplantation should only be considered as a treatment option for a selected subset of patients suffering from HCC. In a prospective study we investigated the clinical relevance of DNA-ploidy for patients receiving liver transplantation due to HCC. Patients and Methods: Between January 1989 and December 1999 115 patients with HCC received a liver transplantation (LTX) presented HCC in the explanted liver. In a prospective study we enrolled 87 patients for which DNA-ploidy data were available. The follow-up period ranged up to 12 years. DNA-ploidy was determined by means of image cytometry on nuclei isolated from paraffin embedded tumor tissue. Results: The results of DNA analysis were related to survival, tumor stage and histopathological grading. Ten years survival was dependent on DNA ploidy 98% with diploid cells, 83% with polyploidy cells and 18% with aneuploid cells. Patients with diploid tumor had no metastasis and no local tumor progression during the follow up time whereas patients with aneuploid tumors suffered from recurrence and local tumor progression. The difference of tumor progression between diploid and aneuploid tumors were highly significant (P<0.001). Tumors were aneuploid in 36%of stage pT1, in 52% of pT2 and in 70%of pT3. In correlation to the histopathological grading, aneuploid cells were found in 4% in G1 tumors, in 67% in G2 tumors and in 96% in G3 tumors. Conclusion. DNA-ploidy appears to be a prognostic factor predicting the clinical outcome of HCC patients after liver transplantation. Thus, the decision to perform an LTX should depend on the results of DNA ploidy after biopsy. While in patients with diploid tumors the indication for LTX may be extended, in patients with aneuploid tumors may be restricted. Further studies to correlate DNA ploidy with the outcome after adjunctive therapy, e.g. chemoembolisation and the combination with LTX are ongoing.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).