BACKGROUND: The serpin SERPINB3 (SB3) found over-expressed in human hepatocellular carcinoma and in regenerating liver in mice has been shown to induce apoptosis resistance, epithelial-to-mesenchymal transition and increasing cellular invasion. It has also been hypothesised that SB3 may provide a pro-proliferative stimulus for liver cells in vivo. No information is available on SB3 in hepatoblastoma (HB). Aims of the study were to analyse SB3 expression in HB specimens and to investigate its possible correlation with Myc expression and tumour extension at diagnosis as evaluated by the pre-treatment extent of disease evaluation system (PRETEXT). METHODS: Frozen tumour specimens from 42 children with HB were analysed for SB3 and Myc expression by real-time PCR. SB3 localisation in tumour specimens was assessed by immunohistochemistry. RESULTS: At transcription level SB3 was positive in 79% of the cases. By immunohistochemistry, SB3 expression was found mainly in the embryonic, blastemal, small cell undifferentiated (SCUD) components of HB, while it was not detectable in normal hepatocytes. High SB3 reactivity was also detected in neoplastic cell clusters of portal vein tumour thrombosis. A direct correlation was observed between SB3 gene expression, the up-regulation of Myc (r=0.598, p<0.0001) and tumour extension (PRETEXT III/IV versus I/II, p=0.013). CONCLUSIONS: SB3 is over-expressed in HB and its expression is positively correlated with Myc expression and high tumour stage. The role of SB3 in the genesis of HB and in defining the risk profile of children affected by this tumour is hypothesised.
BACKGROUND: The serpin SERPINB3 (SB3) found over-expressed in humanhepatocellular carcinoma and in regenerating liver in mice has been shown to induce apoptosis resistance, epithelial-to-mesenchymal transition and increasing cellular invasion. It has also been hypothesised that SB3 may provide a pro-proliferative stimulus for liver cells in vivo. No information is available on SB3 in hepatoblastoma (HB). Aims of the study were to analyse SB3 expression in HB specimens and to investigate its possible correlation with Myc expression and tumour extension at diagnosis as evaluated by the pre-treatment extent of disease evaluation system (PRETEXT). METHODS: Frozen tumour specimens from 42 children with HB were analysed for SB3 and Myc expression by real-time PCR. SB3 localisation in tumour specimens was assessed by immunohistochemistry. RESULTS: At transcription level SB3 was positive in 79% of the cases. By immunohistochemistry, SB3 expression was found mainly in the embryonic, blastemal, small cell undifferentiated (SCUD) components of HB, while it was not detectable in normal hepatocytes. High SB3 reactivity was also detected in neoplastic cell clusters of portal vein tumour thrombosis. A direct correlation was observed between SB3 gene expression, the up-regulation of Myc (r=0.598, p<0.0001) and tumour extension (PRETEXT III/IV versus I/II, p=0.013). CONCLUSIONS:SB3 is over-expressed in HB and its expression is positively correlated with Myc expression and high tumour stage. The role of SB3 in the genesis of HB and in defining the risk profile of children affected by this tumour is hypothesised.
Authors: Sarah A Comerford; Elizabeth A Hinnant; Yidong Chen; Hima Bansal; Shawn Klapproth; Dinesh Rakheja; Milton J Finegold; Dolores Lopez-Terrada; Kathryn A O'Donnell; Gail E Tomlinson; Robert E Hammer Journal: JCI Insight Date: 2016-10-06
Authors: Namratha Sheshadri; Joseph M Catanzaro; Alex J Bott; Yu Sun; Erica Ullman; Emily I Chen; Ji-An Pan; Song Wu; Howard C Crawford; Jianhua Zhang; Wei-Xing Zong Journal: Cancer Res Date: 2014-09-11 Impact factor: 12.701
Authors: C Turato; A Vitale; S Fasolato; M Ruvoletto; L Terrin; S Quarta; R Ramirez Morales; A Biasiolo; G Zanus; N Zali; P S Tan; Y Hoshida; A Gatta; U Cillo; P Pontisso Journal: Br J Cancer Date: 2014-05-08 Impact factor: 7.640