Genomic heterogeneity in synchronous hepatocellular carcinomas

Background-Hepatocellular carcinoma (HCC) arising in cirrhosis is frequentl y multifocal. Whether HCC develops monoclonally or multiclonally is an unre solved question. Of the multiple tumour nodules present in many patients, i t has not been established whether the smaller lesions represent intrahepat ic metastases or de novo cancers. Aims-To assess the degree of genomic heterogeneity in synchronous HCCs in c irrhosis. Methods-The arbitrarily primed polymerase chain reaction technique was util ised to compare the DNA fingerprint of HCCs and regenerative nodules (RNs) removed from cirrhotic explant livers. Results-Polymorphic genomic heterogeneity was noted in 54 HCCs and 31 RNs m icrodissected. Even satellite nodules in close proximity within the same se gment of the liver were found to have distinct genomic patterns. Conclusion-Such genomic heterogeneity in synchronous HCCs may explain poor patient survival after surgical resection. If the smaller tumours are de no vo lesions rather than metastases (as these data suggest), then current con cepts regarding liver resection as a curative treatment modality for HCC ma y require reassessment.