Whole-genome DASL gene expression profiling of hepatocellular carcinoma sub-populations isolated by laser microdissection on formalin-fixed and paraffin-embedded liver tissue samples.

In the last ten years, a multitude of studies focusing on gene expression profiling have attempted to shed light on the molecular and genomic mechanisms leading to hepatocarcinogenesis. One of the downsides of the technology available until recently was that it was limited to RNA extracted from fresh/frozen tissue or cell cultures. Recent advances have made it possible to obtain good quality RNA from formalin-fixed paraffin-embedded (FFPE) tissue, allowing access to a virtually limitless archival resource to be available for retrospective and long-term prospective clinico-pathological studies. Laser-capture microdissection allows the isolation of specific cell populations or of specific microscopic areas of interest from tissue samples. This allows the selective evaluation of gene expression of targeted cell clusters, especially in a very heterogeneous environment as the malignant tissue. In our study, we demonstrated that by laser microdissecting the areas of interest from FFPE tissue we could obtain gene expression signals by running the purified RNA through the Whole Genome DASL assay. A large number of genes were expressed in both subpopulations of hepatocellular carcinoma (classical HCC and cholangiocellular differentiation) as well as in the cirrhotic and non-cirrhotic liver background.