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Breast Cancer Research
Published in: Breast Cancer Research 1/2015

Open Access 01-12-2015 | Research article

ALK alteration is a frequent event in aggressive breast cancers

Authors: Abdul K. Siraj, Shaham Beg, Zeenath Jehan, Sarita Prabhakaran, Maqbool Ahmed, Azhar R.Hussain, Fouad Al-Dayel, Asma Tulbah, Dahish Ajarim, Khawla S. Al-Kuraya

Published in: Breast Cancer Research | Issue 1/2015

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Abstract

Introduction

Breast cancer is the most common female malignancy worldwide and, despite improvements in treatment modalities, there are increased chances of recurrence and metastasis in a substantial number of cases and it remains one of the major causes of mortality among female cancer patients. Anaplastic lymphoma kinase (ALK) gene has been found to be altered in several solid and hematologic tumors. We aimed to comprehensively study the prevalence of ALK expression, and changes in copy number and translocation in a large cohort of breast cancer cases in a Middle Eastern population.

Methods

ALK protein expression was investigated by immunohistochemistry and numerical and structural variations of the ALK gene were analyzed by fluorescence in situ hybridization (FISH) in a tissue microarray format in a cohort of more than 1000 Middle Eastern breast cancers. The data were correlated with clinicopathologic parameters and other important molecular biomarkers.

Results

Immunohistochemical analysis showed ALK overexpression in 36.0 % of the breast cancer patients and gene amplification was present in 13.3 % of cases, seen by FISH analyses. ALK overexpression was significantly associated with ALK gene amplification (p = 0.0031). ALK-overexpressing tumors showed significant association with high-grade tumors (p = 0.0039), ductal histologic subtype (p = 0.0076), triple-negative phenotype (p = 0.0034), and high Ki-67 (p = 0.0001) and p-AKT (p <0.0001).

Conclusions

Immunohistochemical analysis showed ALK is overexpressed in a substantial proportion of breast cancers and possibly plays a significant role in the aggressive behavior of this cancer. Gene amplification is hypothesized to be a possible cause for a significant proportion of this overexpression. Based on these findings, a potential role for an ALK inhibitor, as a therapeutic agent targeting aggressive subtypes of breast cancer, merits further investigation.
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Metadata
Title
ALK alteration is a frequent event in aggressive breast cancers
Authors
Abdul K. Siraj
Shaham Beg
Zeenath Jehan
Sarita Prabhakaran
Maqbool Ahmed
Azhar R.Hussain
Fouad Al-Dayel
Asma Tulbah
Dahish Ajarim
Khawla S. Al-Kuraya
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0610-3

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