Morphologic and genetic heterogeneity in breast fibroepithelial lesions-a comprehensive mapping study.


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
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

1732-1745

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Auteurs

Benjamin Yongcheng Tan (BY)

Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.

Nur Diyana Md Nasir (ND)

Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.

Huan Ying Chang (HY)

Duke-NUS Medical School, Singapore, Singapore.

Cedric Chuan Young Ng (CCY)

Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore.

Peiyong Guan (P)

Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore.
Quantitative Biology and Medicine Programme, Duke-NUS Medical School, Singapore, Singapore.

Sanjanaa Nagarajan (S)

Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore.

Vikneswari Rajasegaran (V)

Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore.

Jing Yi Lee (JY)

Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore.

Jing Quan Lim (JQ)

Lymphoma Genomic Translational Laboratory, National Cancer Centre Singapore, Singapore, Singapore.

Aye Aye Thike (AA)

Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.
Duke-NUS Medical School, Singapore, Singapore.

Bin Tean Teh (BT)

Duke-NUS Medical School, Singapore, Singapore. teh.bin.tean@singhealth.com.sg.
Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore. teh.bin.tean@singhealth.com.sg.

Puay Hoon Tan (PH)

Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore. tan.puay.hoon@singhealth.com.sg.
Duke-NUS Medical School, Singapore, Singapore. tan.puay.hoon@singhealth.com.sg.
Division of Pathology, Singapore General Hospital, Singapore, Singapore. tan.puay.hoon@singhealth.com.sg.

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