Morphologic and genetic heterogeneity in breast fibroepithelial lesions-a comprehensive mapping study.
Adult
Aged
Breast Neoplasms
/ genetics
Class I Phosphatidylinositol 3-Kinases
/ genetics
Female
Fibroadenoma
/ genetics
Genetic Heterogeneity
Humans
Mediator Complex
/ genetics
Middle Aged
Mutation
Phyllodes Tumor
/ genetics
Retinoic Acid Receptor alpha
/ genetics
Tumor Suppressor Protein p53
/ genetics
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
20
01
2020
accepted:
18
03
2020
revised:
18
03
2020
pubmed:
24
4
2020
medline:
21
7
2021
entrez:
24
4
2020
Statut:
ppublish
Résumé
Breast fibroepithelial lesions (FELs) encompass the common fibroadenoma (FA) and relatively rare phyllodes tumour (PT); the latter entity is usually classified as benign, borderline or malignant. Intratumoural heterogeneity is frequently present in these tumours, making accurate histologic evaluation challenging. Despite their rarity, PTs are an important clinical problem due to their propensity for recurrence and, in the case of malignant PT, metastasis. Surgical excision is the mainstay of management. Recent work has uncovered myriad genetic alterations in breast FELs. In this study, exome sequencing was performed on seven cases of morphologically heterogeneous breast FELs, including FAs, PTs of all grades, and a case of metaplastic spindle cell carcinoma arising in PT, in order to elucidate their intratumoural genetic repertoire. Gene mutations identified encompassed cell signalling, tumour suppressor, DNA repair and cell cycle regulating pathways. Mutations common to multiple tumour regions generally showed higher variant allele frequency. Frequent mutations included MED12, TP53, RARA and PIK3CA. Histological observations of increased cellular density and pleomorphism correlated with mutational burden. Phylogenetic analyses revealed disparate pathways of possible tumour progression. In summary, histological heterogeneity correlated with genetic changes in breast FELs.
Identifiants
pubmed: 32322022
doi: 10.1038/s41379-020-0533-0
pii: S0893-3952(22)00702-5
doi:
Substances chimiques
MED12 protein, human
0
Mediator Complex
0
RARA protein, human
0
Retinoic Acid Receptor alpha
0
Tumor Suppressor Protein p53
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1732-1745Références
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