mRNA gene expression correlates with histologically diagnosed chemotherapy-induced hepatic injury
Corresponding Author
Charles H.C. Pilgrim
Division of Cancer Surgery
Departments of Surgery
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Charles Pilgrim, The Alfred Hospital – Upper Gastrointestinal Surgery, Commercial Rd, Melbourne, Vic. 3000, Australia. Tel: +61 3 9076 2000. Fax: +61 3 9076 3902. E-mail: [email protected]Search for more papers by this authorAlan Pham
Department of Pathology, The Alfred Hospital, Melbourne, Victoria, Australia
Search for more papers by this authorMarty Smith
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Search for more papers by this authorVal Usatoff
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Search for more papers by this authorPeter M. Evans
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Search for more papers by this authorSimon Banting
Division of Cancer Surgery
Departments of Surgery
Search for more papers by this authorMichael Michael
Division of Cancer Medicine, Peter MacCallum Cancer Centre
Medicine, University of Melbourne (St. Vincent's Hospital, Melbourne)
Search for more papers by this authorWayne A. Phillips
Division of Cancer Surgery
Departments of Surgery
Search for more papers by this authorCorresponding Author
Charles H.C. Pilgrim
Division of Cancer Surgery
Departments of Surgery
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Charles Pilgrim, The Alfred Hospital – Upper Gastrointestinal Surgery, Commercial Rd, Melbourne, Vic. 3000, Australia. Tel: +61 3 9076 2000. Fax: +61 3 9076 3902. E-mail: [email protected]Search for more papers by this authorAlan Pham
Department of Pathology, The Alfred Hospital, Melbourne, Victoria, Australia
Search for more papers by this authorMarty Smith
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Search for more papers by this authorVal Usatoff
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Search for more papers by this authorPeter M. Evans
Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred Hospital
Search for more papers by this authorSimon Banting
Division of Cancer Surgery
Departments of Surgery
Search for more papers by this authorMichael Michael
Division of Cancer Medicine, Peter MacCallum Cancer Centre
Medicine, University of Melbourne (St. Vincent's Hospital, Melbourne)
Search for more papers by this authorWayne A. Phillips
Division of Cancer Surgery
Departments of Surgery
Search for more papers by this authorThis paper was presented at the AHPBA 2011 meeting in Miami, FL, USA.
Abstract
Introduction: Chemotherapy-induced hepatic injuries (CIHI) are an increasing problem facing hepatic surgeons. It may be possible to predict the risk of developing CIHI by analysis of genes involved in the metabolism of chemotherapeutics, previously established as associated with other forms of toxicity.
Methods: Quantitative reverse transcriptase-polymerase chain reaction methodology (q-RT-PCR) was employed to quantify mRNA expression of nucleotide excision repair genes ERCC1 and ERCC2, relevant in the neutralization of damage induced by oxaliplatin, and genes encoding enzymes relevant to 5-flurouracil metabolism, [thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)] in 233 hepatic resection samples. mRNA expression was correlated with a histopathological injury scored via previously validated methods in relation to steatosis, steatohepatitis and sinusoidal obstruction syndrome.
Results: Low-level DPD mRNA expression was associated with steatosis [odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.53–10.19, P < 0.003], especially when stratified by just those patients exposed to chemotherapy (OR = 4.48, 95% CI = 1.31–15.30 P < 0.02). Low expression of ERCC2 was associated with sinusoidal injury (P < 0.001). There were no further associations between injury patterns and target genes investigated.
Conclusions: Predisposition to the development of CIHI may be predictable based upon individual patient expression of genes encoding enzymes related to the metabolism of chemotherapeutics.
Supporting Information
Table S1 PCR primers.
Table S2 Fresh frozen vs. FFPE target: reference ratio for each target gene.
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| HPB_365_sm_Tab_S1-2.doc38.5 KB | Supporting info item |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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