Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC): prevalence, clinicopathologic features and prognostic implication

PLoS One. 2015 Mar 24;10(3):e0120320. doi: 10.1371/journal.pone.0120320. eCollection 2015.

Abstract

Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients.

Methods: We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining.

Results: Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11-28.44, p = 0.037).

Conclusion: This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Breast / pathology*
  • Female
  • Gene Amplification*
  • Gene Dosage*
  • Humans
  • Inflammatory Breast Neoplasms / diagnosis
  • Inflammatory Breast Neoplasms / epidemiology
  • Inflammatory Breast Neoplasms / genetics*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Survival Analysis
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / epidemiology
  • Triple Negative Breast Neoplasms / genetics

Substances

  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases

Grants and funding

This research was supported by 1) the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2011600), and by 2) a faculty research grant of Yonsei University College of Medicine for 2011 (6-2011-0082). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.