Oncotarget

Research Papers: Pathology:

Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma

Corinne Bouvier _, Nicolas Macagno, Quy Nguyen, Anderson Loundou, Carine Jiguet-Jiglaire, Jean-Claude Gentet, Jean-Luc Jouve, Alexandre Rochwerger, Jean-Camille Mattei, Daniel Bouvard and Sébastien Salas

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Oncotarget. 2016; 7:64702-64710. https://doi.org/10.18632/oncotarget.11876

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Abstract

Corinne Bouvier1,2, Nicolas Macagno1,2, Quy Nguyen1, Anderson Loundou3,4, Carine Jiguet-Jiglaire1, Jean-Claude Gentet5, Jean-Luc Jouve6, Alexandre Rochwerger7, Jean-Camille Mattei1,7, Daniel Bouvard8 and Sébastien Salas1,2

1 Aix-Marseille University (AMU), Faculty of Medecine, CRO2, UMR 911 (Equipe IV), Marseille, France

2 Department of Pathology, APHM, Timone Hospital, Marseille, France

3 Department of Public Health, Aix-Marseille University (AMU), Faculty of Medecine, EA 3270 Research Unit, Marseille, France

4 Department of Research and Innovation, APHM, Timone Hospital, Support Unit for Clinical Research and Economic Evaluation, Marseille, France

5 Department of Pediatric Oncology, APHM, Timone Hospital, Marseille, France

6 Department of Pediatric Orthopaedic Surgery, APHM, Timone Hospital, Marseille, France

7 Department of Adult Orthopaedic Surgery, APHM, Nord Hospital, Marseille, France

8 Institut Albert Bonniot, U823, Grenoble, France

Correspondence to:

Corinne Bouvier, email:

Keywords: osteosarcoma, hippo pathway, YAP/TAZ, beta1 integrin, prognosis, Pathology Section

Received: May 23, 2016 Accepted: August 01, 2016 Published: September 06, 2016

Abstract

Introduction: Currently, very few studies are available concerning the mammalian Hippo pathway in bone sarcomas. YAP/TAZ transcription co-activators are key downstream effectors of this pathway and may also have oncogenic properties. Additionally, recent in-vitro experiments showed that expression of β1-integrin promoted metastasis in osteosarcomas. This study investigated the expression of YAP/TAZ and β1-integrin in human osteosarcomas.

Materials and methods: We performed automated immunohistochemistry on tissue-microarrays (TMA) in which 69 conventional osteosarcomas biopsies performed prior to chemotherapy were embedded. Cellular localization and semi-quantitative analysis of each immunostain was performed using Immunoreactive Score (IRS) and correlated to clinico-pathological data.

Results: Cytoplasmic expression of β1-integrin was noted in 54/59 osteosarcomas (92%), with 33/59 cases (56%) displaying membranous staining. YAP/TAZ was expressed in 27/45 osteosarcomas (60%), with 14 cases (31%) showing cytoplasmic expression while 13 other cases (28%) displayed nuclear expression. No link was found between YAP/TAZ or β1-integrin expression and response to chemotherapy. In univariate analysis, YAP/TAZ immunoreactive score was pejoratively correlated with overall survival (p = 0.01). Expression of β1-integrin on cell membrane was also pejorative for OS (p = 0.045). In multivariate analysis, YAP/TAZ nuclear expression was an independent prognostic factor for PFS (p = 0.035).

Conclusion: this study indicates that β1-integrin and YAP/TAZ proteins are linked to prognosis and therefore could be therapeutic targets in conventional osteosarcomas.


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