ARID1A and CTNNB1/β-Catenin Molecular Status Affects the Clinicopathologic Features and Prognosis of Endometrial Carcinoma: Implications for an Improved Surrogate Molecular Classification

Cancers

Sara Coluccelli¹  Daniela Turchetti¹  AnnaMyriam Perrone¹  Gloria Ravegnini¹  Giovanna Barbero¹  Sabrina Angelini¹  PierandreaDe Iaco¹  Giulia Dondi¹  Donatella Santini¹  Jacopo Lenzi²  AntonioDe Leo³  Giovanni Tallini³  Claudio Ceccarelli³  Claudio Zamagni⁴  Dariode Biase⁵  Marco Grillini⁶ 

[1] Centro di Studio e Ricerca delle Neoplasie Ginecologiche, Alma Mater Studiorum—University of Bologna, 40138 Bologna, Italy;Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum—University of Bologna, via San Giacomo 12, 40126 Bologna, Italy;Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum—University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;IRCCS Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy;Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero—Universitaria di Bologna/Azienda USL di Bologna, 40138 Bologna, Italy;Pathology Unit, IRCCS Azienda Ospedaliero—Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy;

关键词: endometrial cancer;    molecular classification;    ARID1A;    CTNNB1/β-catenin;    prognosis;    high-risk endometrial cancer;   

DOI  :  10.3390/cancers13050950

来源: DOAJ

【 摘 要 】

The collaborative Cancer Genome Atlas (TCGA) project identified four distinct prognostic groups of endometrial carcinoma (EC) based on molecular alterations: (i) the ultramutated subtype that encompasses POLE mutated (POLE) cases; (ii) the hypermutated subtype, characterized by MisMatch Repair deficiency (MMRd); (iii) the copy-number high subtype, with p53 abnormal/mutated features (p53abn); (iv) the copy-number low subtype, known as No Specific Molecular Profile (NSMP). Although the prognostic value of TCGA molecular classification, NSMP carcinomas present a wide variability in molecular alterations and biological aggressiveness. This study aims to investigate the impact of ARID1A and CTNNB1/β-catenin alterations by targeted Next-generation sequencing (NGS) and immunohistochemistry (IHC) in a consecutive series of 125 molecularly classified ECs. NGS and IHC were used to assign surrogate TCGA groups and to identify molecular alterations of multiple target genes including POLE, PTEN, ARID1A, CTNNB1, TP53. Associations with clinicopathologic parameters, molecular subtypes, and outcomes identified NSMP category as the most heterogeneous group in terms of clinicopathologic features and outcome. Integration of surrogate TCGA molecular classification with ARID1A and β-catenin analysis showed NSMP cases with ARID1A mutation characterized by the worst outcome with early recurrence, while NSMP tumors with ARID1A wild-type and β-catenin alteration had indolent clinicopathologic features and no recurrence. This study indicates how the identification of ARID1A and β-catenin alterations in EC represents a simple and effective way to characterize NSMP tumor aggressiveness and metastatic potential.

【 授权许可】

Unknown