EXPRESSION OF PROLIFERATION-ASSOCIATED ANTIGENS AND DETECTION OF NUMERICAL CHROMOSOME-ABERRATIONS IN PRIMARY HUMAN LIVER-TUMORS - RELEVANCETO TUMOR CHARACTERISTICS AND PROGNOSIS

Aims-To assess cell proliferation and the presence of numerical chromo some aberrations involving chromosomes 1 and 8 in benign and malignant liver tumours. Methods-Cell proliferation was studied immunohistochem ically in paraffin wax embedded material from 62 primary liver tumours (20 hepatocellular carcinomas, 16 cholangiocellular carcinomas, 15 li ver cell adenomas, 11 focal nodular hyperplasias), and the results wer e compared with histological characteristics and clinical data. Copy n umbers of chromosomes 1 and 8 were assessed by interphase fluorescence in situ hybridisation (FISH) with satellite probes in fresh tumour ma terial. Results-The expression of proliferation associated antigen Ki6 7, using the monoclonal antibody MIB-1, and proliferating cell nuclear antigen (PCNA), using the antibody PC10, was found to be significantl y higher in malignant versus benign liver tumours. Neither Ki67 nor PC NA expression were independent prognostic parameters. However, there w as a tendency for a worse outcome (survival < 12 months) for patients with a high MIB-1 labelling index (> 20%) compared with patients havin g the same tumour stage and a low MIB-1 index. Aneusomy for chromosome s 1 and 8 was demonstrated by FISH in malignant tumours (six of seven hepatocellular carcinomas, four of five cholangiocellular carcinomas) but not in benign tumours (none of nine) or non-neoplastic liver (none of nine). Conclusion-Both the determination of the proliferating cell fraction and FISH analysis are useful for distinguishing hepatocellul ar carcinoma from liver cell adenoma or focal nodular hyperplasia; hig h fractions of proliferating cells are predictive of an early relapse.