Z Gastroenterol 2010; 48 - P2_75
DOI: 10.1055/s-0029-1246454

Lipid droplet-associated PAT-proteins show frequent and differential expression in neoplastic steatogenesis

BK Straub 1, E Herpel 1, S Singer 1, LM Pawella 2, R Zimbelman 3, K Breuhahn 4, S Macher-Goeppinger 4, A Warth 5, J Lehmann-Koch 1, T Longerich 1, H Heid 3, P Schirmacher 4
  • 1Pathologisches Institut der Universität Heidelberg, Heidelberg, Heidelberg
  • 2Institut für Pathologie, Heidelberg, Heidelberg
  • 3Abteilung Zellbiologie, DKFZ, Heidelberg
  • 4Uniklinik Heidelberg, Institut für Pathologie, Heidelberg
  • 5Institut für Pathologie, Universitätsklinik Heidelberg, Heidelberg

In many human cancers, lipogenic pathways are activated; in some tumors, such as hepatocellular carcinoma (HCC), this is reflected by the presence of visible lipid droplets (LDs). Yet, the biology of steatogenesis in malignant tumors is largely unknown. We have recently demonstrated that LD-associated proteins of the PAT-family, named after their constituents perilipin, adipophilin, and TIP47, are differentially expressed in hepatic steatogenesis.

We have comprehensively investigated PAT-expression in neoplastic steatogenesis as well as in respective normal tissues with immunohistology and electron microscopy as well as protein biochemical and molecular biological methods. By staining for PAT-proteins, LD-accumulation was found to be a frequent phenomenon of carcinoma cells. Whereas adipophilin and TIP47 stained almost ubiquitously the rim of LDs in various tumor types, especially those with clear cell phenotype, perilipin was restricted to LDs of hepatocellular, sebaceous, and lipomatous tumors. In HCC, perilipin, adipophilin, and TIP47 were coexpressed, and showed regional heterogeneity with a predominantly mutually exclusive localization pattern. In stepwise carcinogenesis, adipophilin expression correlated with the proliferation rate and was upregulated during early tumorigenesis, whereas perilipin was often lost during hepatocarcinogenesis.

In conclusion, expression analysis of PAT-proteins demonstrated that by far more carcinomas of hepatocellular and other origin contain (PAT-positive) LDs than expected by conventional light microscopy. PAT-proteins are differentially expressed in different tumor types and thus may support diagnostic considerations; for instance perilipin may help establish hepatocellular origin in metastases of unknown primary. Since inhibition of lipogenesis has been shown to exert anti-neoplastic effects, PAT-proteins may represent targets for interventive strategies.

adipophilin - hepatocellular carcinoma - lipid droplet - perilipin - steatogenesis