Molecular characterization of metaplastic breast carcinoma via next generation sequencing.
Hum Pathol. 2018 Dec 08;:
Authors: Zhai J, Giannini G, Ewalt MD, Zhang EY, Invernizzi M, Niland J, Lai LL
Abstract
Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer with variable morphology. MBC is more often triple negative (ER-, PR-, HER2-) and is associated with poorer clinical outcome when compared to infiltrating ductal carcinoma. The purpose of our study is to identify molecular alterations in MBC using next generation sequencing (NGS) which may aid chemotherapy selection and use of targeted therapy. A cohort of 18 patients with MBC yielded adequate DNA from microdissected formalin fixed and paraffin embedded (FFPE) tumor blocks. NGS was performed using the Ion AmpliSeq cancer hotspot mutation panel version 2 kit by Life Technologies, which targets hotspot regions in 50 genes. Immunohistochemical stains for androgen receptor (AR), and programmed cell death -ligand 1 (PD-L1) were performed. A total of 23 genetic alterations were identified in 15 of 18 patients (83.3%). Eleven genetic alterations in the PI3K signaling pathway were identified in 9 of 18 patients (50.0%), including 7 PIK3CA mutations (38.9%), 3 PTEN genetic alterations (16.7%), and 1 AKT1 mutation (5.6%). Ten of 18 patients (55.6%) each harbored one TP53 genetic alteration. Additional genetic alterations identified were one HRAS mutation and one ATM mutation. AR immunoreactivity was identified in 2 of 18 patients (11.1%). PD-L1 was negative in all patients. NGS analysis demonstrated that PI3K pathway related genetic alterations were detected in a high percentage of MBC, suggesting that targeting the PI3K/mTOR pathway may be promising in patients with MBC. In addition, patients with AR expressing MBC may benefit from androgen antagonist treatment.
PMID: 30537493 [PubMed - as supplied by publisher]
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