[Clinical implications of spontaneous and iatrogenic dissemination of tumor cells in patients with primary liver cancer].

Abstract

Prognosis of patients with primary liver cancer (PLC) often depends on tumor recurrence and development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test detecting both spontaneous circulation of tumor cells and spread of liver cells due to chemoembolization and alcoholization. By RT-PCR we looked for cells expressing alphafetoprotein (AFP) mRNA in peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers and 37 healthy individuals). By spiking blood of healthy volunteers with HepG2 cells we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leucocytes. All 102 controls scored negative. In contrast, 28 patients (33.3%) with PLC scored positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, one hour and 24 hours after loco-regional therapy: 9 scored positive either one or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful to evaluate the risk of developing extrahepatic metastases. Finally, we are developing new strategies to characterize cells iatrogenically spread into the blood and to define their metastatic potential.