Oncotarget

Research Papers:

ERBB2 mutation is associated with a worse prognosis in patients with CDH1 altered invasive lobular cancer of the breast

Zheng Ping, Gene P. Siegal, Shuko Harada, Isam-Eldin Eltoum, Mariam Youssef, Tiansheng Shen, Jianbo He, Yingjie Huang, Dongquan Chen, Yiping Li, Kirby I Bland, Helena R Chang and Dejun Shen _

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Oncotarget. 2016; 7:80655-80663. https://doi.org/10.18632/oncotarget.13019

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Abstract

Zheng Ping1, Gene P. Siegal1,6, Shuko Harada1,6, Isam-Eldin Eltoum1,6, Mariam Youssef1, Tiansheng Shen1, Jianbo He3, Yingjie Huang7, Dongquan Chen4,6, Yiping Li2,6, Kirby I Bland5,6, Helena R Chang8, Dejun Shen1,6

1Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

2Division of Cell and Molecular Pathology, Departments of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

3Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

4Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

5Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

6UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

7Ningbo Clinical and Pathological Diagnosis Center, Ningbo, Zhejiang, China

8Revlon/UCLA Breast Center, Department of Surgery, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA

Correspondence to:

Dejun Shen, email: [email protected]

Keywords: invasive lobular carcinoma, CDH1 mutation, ERBB2 mutation, genomics, TCGA

Received: September 09, 2016     Accepted: October 24, 2016     Published: November 02, 2016

ABSTRACT

E-cadherin (CDH1) is a glycoprotein that mediates adhesion between epithelial cells and also suppresses cancer invasion. Mutation or deletion of the CDH1 gene has been reported in 30–60% cases of invasive lobular carcinoma (ILC). However, little is known about genomic differences between ILC with and without a CDH1 alteration. Therefore, we analyzed whole genome sequencing data of 169 ILC cases from The Cancer Genome Atlas (TCGA) to address this deficiency. Our study shows that CDH1 gene was altered in 59.2% (100/169) of ILC. No significant difference was identified between CDH1-altered and -unaltered ILC cases for any of the examined demographic, clinical or pathologic characteristics, including histologic grade, tumor stage, lymph node metastases, or ER/PR/HER2 states. Seven recurrent mutations (PTEN, MUC16, ERBB2, FAT4, PCDHGA2, HERC1 and FLNC) and four chromosomal changes with recurrent copy number variation (CNV) (11q13, 17q12-21, 8p11 and 8q11) were found in ILC, which correlated with a positive or negative CDH1 alteration status, respectively. The prevalence of the most common breast cancer driver abnormalities including TP53 and PIK3CA mutations and MYC and ERBB2 amplifications showed no difference between the two groups. However, CDH1-altered ILC with an ERBB2 mutation shows a significantly worse prognosis compared to its counterparts without such a mutation. Our study suggests that CDH1-altered ILC patients with ERBB2 mutations may represent an actionable group of patients who could benefit from targeted breast cancer therapy.


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