Are both distinct epithelial and stromal cells molecular analysis from phyllodes tumors versus fibroadenoma components affected in breast fibroepithelial progression?

Autor:	Waitzberg ÂFL; Universidade Federal de São Paulo - Paulista School of Medicine - Department of Pathology - São Paulo (SP), Brazil., Ferreira ENE; Universidade Federal de São Paulo - Paulista School of Medicine - Department of Pathology - São Paulo (SP), Brazil., Pinilla M; Universidad de Concepción - Facultad de Medicina - Department of Medical Technology - Concepción, Chile., Pineda P; Hospital A C Camargo - Genomics and Molecular Biology Group - São Paulo (SP), Brazil., Malinverni ACM; Universidade Federal de São Paulo - Paulista School of Medicine - Department of Pathology - São Paulo (SP), Brazil.; Universidade Federal de São Paulo - Laboratory of Molecular and Experimental Pathology I - São Paulo (SP), Brazil., Soares FA; Hospital A C Camargo - Department of Anatomic Pathology - São Paulo (SP), Brazil., Carraro DM; Hospital A C Camargo - Genomics and Molecular Biology Group - São Paulo (SP), Brazil.
Jazyk:	angličtina
Zdroj:	Acta cirurgica brasileira [Acta Cir Bras] 2023 Dec 04; Vol. 38, pp. e386823. Date of Electronic Publication: 2023 Dec 04 (Print Publication: 2023).
DOI:	10.1590/acb386823
Abstrakt:	Purpose: To determine molecular events involved in the tumorigenesis of phyllodes tumors (PT) and the role of each stromal (SC) and epithelial (EC) cell. Methods: Frozen breast samples enriched with epithelial and stromal cells from three fibroadenomas and 14 PT were retrieved and laser microdissected. Sanger and polymerase chain reaction-based sequencing of exon 2 MED12 and TERT promoter hotspot mutations were performed; 44K microarray platform was used to analyze gene expression. Results: All three fibroadenomas (FAs) presented mutations in MED12, but not in TERT, whose mutation was observed in five of the 14 PTs. EC and SC of each affected tumor displayed identical alterations. Of the total differentially expressed genes (DEG) (EC = 1,543 and SC = 850), 984 were EC-eDEGs and 291 were SC-eDEGs. We found a high similarity of diseases and functions enriched by both cell types, but dissimilarity in the number of enriched canonical pathways. Three signaling canonical pathways overlapping with EC and SC were predicted to be activated in one cell type and inactivated in the other, while no overlap in eDEGs was assigned to them. We also identified 13 EC-eDEGs and five SC-eDEGs enriched networks, in which the SC-eDEGs were able to segregate FA from PT samples. Conclusions: Identical TERT mutations from both SC and ES origins might affect the PTs tumorigenesis. Gene expression differences suggest coordinated molecular processes between these components with determinant differences acquired by SC, able to fully distinguish PTs from FAs lesions.
Databáze:	MEDLINE
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