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2016 ; 7
(40
): 64702-64710
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Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and
?1-integrin in conventional osteosarcoma
#MMPMID27608849
Bouvier C
; Macagno N
; Nguyen Q
; Loundou A
; Jiguet-Jiglaire C
; Gentet JC
; Jouve JL
; Rochwerger A
; Mattei JC
; Bouvard D
; Salas S
Oncotarget
2016[Oct]; 7
(40
): 64702-64710
PMID27608849
show ga
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 ?1-integrin
promoted metastasis in osteosarcomas. This study investigated the expression of
YAP/TAZ and ?1-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 ?1-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 ?1-integrin expression and
response to chemotherapy. In univariate analysis, YAP/TAZ immunoreactive score
was pejoratively correlated with overall survival (p = 0.01). Expression of
?1-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 ?1-integrin and
YAP/TAZ proteins are linked to prognosis and therefore could be therapeutic
targets in conventional osteosarcomas.
|Adaptor Proteins, Signal Transducing/*metabolism
[MESH]
|Adolescent
[MESH]
|Adult
[MESH]
|Aged
[MESH]
|Bone Neoplasms/*diagnosis/epidemiology
[MESH]
|Child
[MESH]
|Child, Preschool
[MESH]
|Female
[MESH]
|Hippo Signaling Pathway
[MESH]
|Humans
[MESH]
|Infant
[MESH]
|Integrin beta1/*metabolism
[MESH]
|Intracellular Signaling Peptides and Proteins/*metabolism
[MESH]
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