title: Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC): prevalence, clinicopathologic features and prognostic implication.
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).
  
  
  CONCLUSIONS
  This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.
authors: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: Min Hwan
authors: MH
authors: Kim
authors: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: Soohyeon
authors: S
authors: Lee
authors: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors: Ja Seung
authors: JS
authors: Koo
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Kyung Hae
authors: KH
authors: Jung
authors: Center for Breast Cancer, National Cancer Center, Goyang, Korea; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: In Hae
authors: IH
authors: Park
authors: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors: Joon
authors: J
authors: Jeong
authors: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors: Seung Il
authors: SI
authors: Kim
authors: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors: Seho
authors: S
authors: Park
authors: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors: Hyung Seok
authors: HS
authors: Park
authors: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors: Byeong-Woo
authors: BW
authors: Park
authors: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: Joo-Hang
authors: JH
authors: Kim
authors: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: Joohyuk
authors: J
authors: Sohn
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001940:Breast / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases