Prognostic value of the Hippo pathway transcriptional coactivators ă YAP/TAZ and beta 1-integrin in conventional osteosarcoma
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Introduction: Currently, very few studies are available concerning the ă mammalian Hippo pathway in bone sarcomas. YAP/TAZ transcription ă co-activators are key downstream effectors of this pathway and may also ă have oncogenic properties. Additionally, recent in-vitro experiments ă showed that expression of beta 1-integrin promoted metastasis in ă osteosarcomas. This study investigated the expression of YAP/TAZ and ă beta 1-integrin in human osteosarcomas. Materials and methods: We performed automated immunohistochemistry on ă tissue-microarrays (TMA) in which 69 conventional osteosarcomas biopsies ă performed prior to chemotherapy were embedded. Cellular localization and ă semi-quantitative analysis of each immunostain was performed using ă Immunoreactive Score (IRS) and correlated to clinico-pathological data. Results: Cytoplasmic expression of beta 1-integrin was noted in 54/59 ă osteosarcomas (92%), with 33/59 cases (56%) displaying membranous ă staining. YAP/TAZ was expressed in 27/45 osteosarcomas (60%), with 14 ă cases (31%) showing cytoplasmic expression while 13 other cases (28%) ă displayed nuclear expression. No link was found between YAP/TAZ or beta ă 1-integrin expression and response to chemotherapy. In univariate ă analysis, YAP/TAZ immunoreactive score was pejoratively correlated with ă overall survival (p = 0.01). Expression of beta 1-integrin on cell ă membrane was also pejorative for OS (p = 0.045). In multivariate ă analysis, YAP/TAZ nuclear expression was an independent prognostic ă factor for PFS (p = 0.035). Conclusion: this study indicates that beta 1-integrin and YAP/TAZ ă proteins are linked to prognosis and therefore could be therapeutic ă targets in conventional osteosarcomas.
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