Patterns of methylation profiles as diagnostic markers for multiple hepatocellular carcinomas

Abstract

Background: Hepatocellular carcinoma often displays multiple tumor nodules, thus posing a problem for differential diagnosis between cancers of both multifocal and metastatic origin. Conventionally, pathological criteria have been used for this purpose, but these are largely subjective. In order to facilitate a more objective differential diagnosis of multiple HCCs, we used the patterns of methylation of p16 ^INK4a , p14 ^ARF , and GSTP1 genes as markers for each tumor nodule. Methods: Sixty‐seven nodules from 30 cases of multiple or recurrent HCCs were examined using methylation‐specific PCR (MSP) analysis for the detection of methylation profiles. Results: Hypermethylation was detected in 56.7%, 43.3% and 17.9% of the cases for p16 ^INK4a , p14 ^ARF , and GSTP1 genes, respectively. At the genetic level the inter‐nodule methylation profiles were heterogeneous in 23 of the cases and homogeneous in another 7, enabling a multifocal origin to be diagnosed in the former and metastatic origin in the latter. Conclusions: Methylation profiling seems to be useful in differentiating the clonal origins of multiple cancers, as the information yielded by this method is essentially objective.

• Clonality
• GSTP1
• hepatocellular carcinoma
• hypermethylation
• p14ARF
• p16INK4a