Sarcomatoid adrenocortical carcinoma: a comprehensive pathological, immunohistochemical, and targeted next-generation sequencing analysis

Antonella Coli, Thomas G. Papathomas, Eleonora Duregon, Esther Korpershoek, David F. Restuccia, Ronald Van Marion, Rocco Cappellesso, Nathalie Sturm, Giulio Rossi, Nicola Zucchini, Hans Stoop, Wolter Oosterhuis, Laura Ventura, Marco Volante, Ambrogio Fassina, Winand N.M. Dinjens, Mauro Papotti, Ronald R. De Krijger

Risultato della ricerca: Contributo in rivistaArticolo in rivista

15 Citazioni (Scopus)

Abstract

Adrenocortical carcinomas (ACCs) with sarcomatous areas represent an extremely rare type of highly aggressive malignancy of unknown molecular pathogenesis. The current study was planned to gain insight into its molecular genetics using a targeted next-generation sequencing approach and to explore the status of epithelial-mesenchymal transition (EMT)-associated markers (E-/P-/N-cadherins, MMP-2/-9 and caveolin-1), downstream transcriptional regulators of EMT-related signaling pathways (ZEB-1/-2, Slug), stem cell factors (Oct3/4, LIN28, SOX2, SO17, NANOG, CD133, nestin), and markers of adrenocortical origin/tumorigenesis (SF-1, β-catenin, p53) in phenotypically diverse tumor components of 6 cases. Thirteen pathogenic variants of ACC-associated TP53 and CTNNB1 genes were detected in epithelial and/or nonepithelial components in 4 out of 6 tumors. Three cases had identical mutations in distinct components, 1 of which contained TP53/CTNNB1 in 3 out of 5 components, whereas 1 harbored a single TP53 mutation only in the nonepithelial component. By immunohistochemistry, SF-1 and E-/P-/N-cadherins were found positive only in the epithelial component of all cases, whereas the nonepithelial components were mainly enriched for nestin, ZEB-1, and MMP-2/-9. β-Catenin demonstrated an aberrant nuclear localization in the sarcomatoid component of 5 cases, whereas p53 was strongly positive in nonepithelial constituent in 4 of 6 cases. In summary, we have shown that Wnt/β-catenin signaling pathway dysregulation and mutational inactivation of TP53 are common genetic events in sarcomatoid ACCs, a subset of which being monoclonal in origin. These tumors are enriched for EMT-related markers and stem cell factors, potentially conferring a poor prognosis, which might be exploited as novel therapeutic targets.
Lingua originaleEnglish
pagine (da-a)113-122
Numero di pagine10
RivistaHuman Pathology
Volume58
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Adrenocortical carcinoma, sarcomatoid, mutations, epithelial-mesenchymal transition, nestin

Fingerprint

Entra nei temi di ricerca di 'Sarcomatoid adrenocortical carcinoma: a comprehensive pathological, immunohistochemical, and targeted next-generation sequencing analysis'. Insieme formano una fingerprint unica.

Cita questo