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Gene Expression Analysis Offers Unique Advantages to Histopathology in Liver Biopsy Evaluations

¹ National Center for Toxicogenomics and
² Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Correspondence: Address correspondence to: Richard S. Paules, Director, NIEHS Microarray Group, National Institute of Environmental Health Sciences, 111 Alexander Drive, Mail Drop D2-03, P.O. Box 12233, Research Triangle Park, NC 27709-2233, USA; e-mail:paules{at}niehs.nih.gov

Liver diseases that induce nonuniform lesions often give rise to greatly varying histopathology results in needle biopsy samples from the same patient. This study examines whether gene expression analysis of such biopsies could provide a more representative picture of the overall condition of the liver. We utilized acetaminophen (APAP) as a model hepatotoxicant that gives a multifocal pattern of necrosis following toxic doses. Rats were treated with a single toxic or subtoxic dose of APAP and sacrificed 6, 24, or 48 hours after exposure. Left liver lobes were harvested, and both gene expression and histopathological analysis were performed on biopsy-sized samples. While histopathological evaluation of such small samples revealed significant sample to sample differences after toxic doses of APAP, gene expression analysis provided a very homogeneous picture and allowed clear distinction between subtoxic and toxic doses. The main biological function differentiating animals that received sub-toxic from those that had received toxic doses was an acute stress response at 6 hours and signs of energy depletion at later time points. Our results suggest that the use of genomic analysis of biopsy samples together with histopathological analysis could provide a more precise representation of the overall condition of a patient’s liver than histopathological evaluation alone.

Key Words: Histopathology • toxicogenomics • liver • microarray • biopsy • acetaminophen

Abbreviations: APAP, acetaminophen • DEGs, Differentially Expressed Genes • H&E, hematoxylin and eosin • PCA, Principal Component Analysis • PC1, Principal Component 1 • PC2, Principal Component 2

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