Journal Article

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

Ng, Cedric Chuan Young, Tan, Puay Hoon, Chang, Huan Ying, Rajasegaran, Vikneswari, Nagarajan, Sanjanaa, Thike, Aye Aye, Md Nasir, Nur Diyana, Guan, Peiyong, Lim, Jing Quan, Teh, Bin Tean, Lee, Jing Yi, Tan, Benjamin Yongcheng

2020

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited
• Subject: 14/63 / 631/208/514/2254 / 692/420/755 / Adult / Aged / Breast / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cell cycle / Class I Phosphatidylinositol 3-Kinases - genetics / DNA repair / Female / Fibroadenoma / Fibroadenoma - genetics / Fibroadenoma - pathology / Gene frequency / Gene mapping / Genetic Heterogeneity / Humans / Laboratory Medicine / Lesions / Mediator Complex - genetics / Medicine / Medicine & Public Health / Metastases / Middle Aged / Mutation / p53 Protein / Pathology / Phyllodes Tumor - genetics / Phyllodes Tumor - pathology / Phylogeny / Pleomorphism / Retinoic Acid Receptor alpha - genetics / Signal transduction / Tumor Suppressor Protein p53 - genetics / Tumors