Frequent alterations of HER2 through mutation, amplification, or overexpression in pleomorphic lobular carcinoma of the breast
Journal
Breast Cancer Research and Treatment
Journal Volume
150
Journal Issue
2
Pages
447-455
Date Issued
2015
Author(s)
Abstract
Mutations in HER2 gene have been identified in a small subset of breast cancer cases. Identification of HER2 mutation has therapeutic implications for breast cancer, but whether a subgroup of breast cancer with a higher frequency of HER2 mutation exists, remains unknown. We analyzed HER2 mutation and pathologic factors on 73 formalin-fixed, paraffin-embedded samples, including 21 pleomorphic invasive lobular carcinoma (p-ILC) cases, 3 pleomorphic lobular carcinoma in situ (p-LCIS) cases, and 49 classic invasive lobular carcinoma (c-ILC) cases. Mutations were identified through direct sequencing. HER2 overexpression and amplification were determined through immunohistochemistry and fluorescent in situ hybridization. Six mutations were identified, including five in the 24 p-ILC or p-LCIS (p-ILC/p-LCIS) cases (20.8?%) and one in the 49 c-ILC cases (2.0?%), and the difference in frequency was significant (p?=?0.013). Eight of the 24 (33.3?%) p-ILC/p-LCIS cases exhibited HER2 amplification or overexpression (amplification/overexpression), which was significantly higher than in the c-ILC cases (1/49, 2?%). Mutation and amplification/overexpression were mutually exclusive. HER2 mutations were identified more frequently in the p-ILC/p-LCIS cases with extensive apocrine change (p?=?0.018). Combined HER2 alterations through mutation or amplification/overexpression were more frequently identified in p-ILC/p-LCIS cases without estrogen receptor expression. The high frequency (54.1?%, 13/24) of combined HER2 alterations in the p-ILC/p-LCIS cases suggests a crucial role of HER2 in the pathogenesis of p-ILC/p-LCIS. Because of the reported responsiveness of HER2 mutation to anti-HER2 therapy, p-ILC patients without HER2 amplification/overexpression should receive HER2 mutation analysis to identify this therapeutically relevant target. ? 2015, Springer Science+Business Media New York.
SDGs
Other Subjects
epidermal growth factor receptor 2; ERBB2 protein, human; breast tumor; female; gene amplification; gene expression; gene frequency; genetics; human; lung carcinoma; metabolism; mutation; nucleotide sequence; pathology; Base Sequence; Breast Neoplasms; Carcinoma, Lobular; DNA Mutational Analysis; Female; Gene Amplification; Gene Expression; Gene Frequency; Humans; Mutation; Receptor, ErbB-2
Publisher
Springer New York LLC
Type
journal article