Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Strobl, P.
Evaluation of c-MET as a predictive marker for response to sorafenib in advanced hepatocellular carcinoma
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2017. pp. 63
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Jahn Stephan
- Lackner Karoline
- Stauber Rudolf
- Altmetrics:
- Abstract:
- Background and aims: Sorafenib is a multikinase inhibitor approved for the treatment of advanced stage hepatocellular carcinoma (HCC). However, its utility is impaired by development of resistance via activation of the met oncogene (c-MET) escape pathways. Treatment response may be related to the expression level of c-MET in HCCs. Furthermore, c-MET expression is also an important predictor of response to the c-MET inhibitor tivantinib, a potential second-line treatment for HCC. Expression of c-MET is usually assessed in a semiquantitative fashion using immunohistochemistry (IHC) and standardised evaluation criteria, a method prone to intra- and interobserver bias. C-MET expression can also be evaluated quantitatively using the mRNA in situ hybridisation assay RNA scope and digital image analysis (morphometry.) In our study, we first aimed to compare c-MET IHC and RNA scope for the assessment of c-MET expression. Second, we wanted to evaluate the utility of c-MET protein and RNA expression as prognostic and predictive markers for patients with advanced HCC. Material and Methods: FFPE (formalin-fixed, paraffin-embedded) samples of 19 HCC patients, BCLC stages C and D, who received treatment with sorafenib were studied. Response to treatment was assessed using the modified response evaluation criteria in solid tumors (m-RECIST). C-MET expression in HCC tissue was assessed by IHC using the CONFIRM anti-Total c-MET antibody and with RNA scope. Protein and RNA expression was analysed semiquantitatively using light microscopy and numerical scores and quantitatively using digital image analysis. Response to treatment with sorafenib and survival of patient groups with low and high c-MET expression was compared by Kaplan-Meier method and log rank -test. Results: The RNA Scope assay provided quantitative results comparable to the results obtained by semiquantitative IHC scoring. C-MET expression, regardless if measured quantitatively or semiquantitatively by IHC or RNA scope did not differ between patients responding versus those not responding to sorafenib. In addition, overall survival did not differ. Conclusions: C-MET RNA scope is a valuable tool to minimize intra- and interobserver bias in the evaluation of c-MET expression in HCC. Contrary to previous research, this study did not find a difference in c-MET expression in respect to response to sorafenib in patients with advanced HCC.