Altered expression of noncanonical Wnt pathway genes in paediatric and adult adrenocortical tumours. (19th May 2014)

• Record Type: Journal Article
• Authors: Mermejo, Livia M.; Leal, Leticia F.; Colli, Leandro M.; Fragoso, Maria C.B.V.; Latronico, Ana C.; Tone, Luiz G.; Scrideli, Carlos A.; Tucci, Silvio; Martinelli, Carlos E.; Yunes, Jose A.; Mastellaro, Maria J.; Seidinger, Ana L.; Brandalise, Silvia R.; Moreira, Ayrton C.; Ramalho, Leandra N.; Antonini, Sonir R.; Castro, Margaret
• Is Part Of: Clinical endocrinology. Volume 81:Number 4(2014:Oct.)
• Page Start: 503
• Page End: 510
• Publication Date: 2014-05-19
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12462
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12462-abs-0001"> <title>Summary</title> <sec id="cen12462-sec-0001" sec-type="section"> <title>Context</title> <p>The role of planar cell polarity (Wnt/PCP) and calcium‐dependent (Wnt/Ca) noncanonical Wnt pathways in adrenocortical tumours (ACTs) is unknown.</p> </sec> <sec id="cen12462-sec-0002" sec-type="section"> <title>Objectives</title> <p>To investigate the gene expression of Wnt/PCP and Wnt/Ca pathways and its association with <italic>TP53</italic> p.R337H and <italic>CTNNB1</italic> mutations in paediatric and adult ACTs and to correlate these findings with clinical outcome.</p> </sec> <sec id="cen12462-sec-0003" sec-type="section"> <title>Patients</title> <p>Expression of noncanonical Wnt‐related genes was evaluated in 91 ACTs (66 children and 25 adults) by qPCR and the expression of beta‐catenin, P53 and protein effectors of Wnt/Ca (NFAT) and Wnt/PCP (JNK) by immunohistochemistry. <italic>TP53</italic> and <italic>CTNNB1</italic> genes were sequenced.</p> </sec> <sec id="cen12462-sec-0004" sec-type="section"> <title>Results</title> <p> <italic>TP53</italic> p.R337H mutation frequency was higher in children (86% <italic>vs</italic> 28%), while <italic>CTNNB1</italic> mutation was higher in adults (32% <italic>vs</italic> 6%). Mortality was higher in adults harbouring <italic>TP53</italic> p.R337H and in children with <italic>CTNNB1</italic> mutations. Overexpression of <italic>WNT5A, </italic> Wnt/Ca ligand, was observed in children and adults. Overexpression of <italic>MAPK8</italic> and underexpression of <italic>PRICKLE</italic>, Wnt/PCP mediators, were observed in paediatric but not in adult cases. Cytoplasmic/nuclear beta‐catenin and P53 accumulation was observed in the majority of paediatric and adult ACTs as well as NFAT and JNK. Overexpression of <italic>MAPK8</italic> and underexpression of <italic>PRICKLE</italic> were associated with mortality in children, while overexpression of <italic>WNT5A</italic> and underexpression of <italic>PRICKLE</italic> were associated with mortality in adults.</p> </sec> <sec id="cen12462-sec-0005" sec-type="section"> <title>Conclusions</title> <p>In our study, <italic>TP53</italic> p.R337H and <italic>CTNNB1</italic> mutations correlated with poor prognosis in adults and children, respectively. We demonstrate, for the first time, the activation of Wnt/PCP and Wnt/Ca noncanonical pathway genes, and their association with poor outcome in children and adults, suggesting their putative involvement in ACTs aggressiveness.</p> </sec> </abstract>