Here we report an analysis of the role of HGF/c-Met related β-catenin activation and CTNNB1 mutation activation of β-catenin in a large cohort of 84 patients with hepatoblastoma.

This characterisation of β-catenin activation by the c-Met pathway may have clinical relevance because several HGF/c-Met small molecule inhibitors are now in early phase clinical trials. Materials and methods Patients and SIOPEL HB clinical trials SIOPEL Liver tumor clinical trials are international, prospective, clinical Apoptosis Compound Library trials run under the auspices of the SIOP Liver Tumor Strategy Group (SIOPEL). Our cohort comprises patients prospectively enrolled into the SIOPEL 3 clinical trial, a randomised study which opened in March 1998, designed to evaluate the effectiveness of preoperative chemotherapy for standard risk (SR) HB with either cisplatin (CDDP) alone or in combination with SB431542 research buy doxorubicin (PLADO). A detailed description of the SR patient cohort, its clinical features, staging and outcome has previously been reported [33]. SIOPEL 3 patients with high risk (HR) HB were all treated preoperatively with SUPERPLADO, a three-drug combination of Cisplatin, Doxorubicin and Carboplatin and the results have been reported [34]. All patients were recruited to the SIOPEL 3 clinical trial

with appropriate informed consent. This specific study was reviewed and approved by the New Zealand Health Research Council Multi-regional ethics committee (MREC). Tumor samples In this study we have accessed a representative cohort

of 84 HB patients with clinical, histologic and survival data available for most samples. Both diagnostic and post-chemotherapy samples were available for fourteen patients bringing the total number of samples analysed to 98. In the case of diagnostic samples there was generally just a single formalin-fixed paraffin-embedded (FFPE) tumor block available containing the entire biopsy material on which the diagnosis was made. For each post-chemotherapy Verteporfin supplier case, the most representative FFPE block was identified by examination of slides stained with haematoxylin and eosin (H+E). From the H+E slides, representative tumor and adjacent normal tissue areas were selected by a pathologist (C.M.) for subsequent tissue array construction. Tissue Array Construction A tissue microarray (TMA) was constructed by depositing a 1 mm core of each tumor or normal tissue into a wax recipient block using the Manual Tissue Arrayer I (Beecher Instruments Inc., Sun Prairie, WI, USA). In cases where tumor heterogeneity was evident, different representative areas of the tumor were sampled for TMA construction.