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

 Min Hwan Kim  ;  Soohyeon Lee  ;  Ja Seung Koo  ;  Kyung Hae Jung  ;  In Hae Park  ;  Joon Jeong  ;  Seung Il Kim  ;  Seho Park  ;  Hyung Seok Park  ;  Byeong-Woo Park  ;  Joo-Hang Kim  ;  Joohyuk Sohn 
 PLOS ONE, Vol.10(3) : e0120320, 2015 
Journal Title
Issue Date
Adult ; Aged ; 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
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.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Min Hwan(김민환) ORCID logo https://orcid.org/0000-0002-1595-6342
Kim, Seung Il(김승일)
Kim, Joo Hang(김주항)
Park, Byeong Woo(박병우) ORCID logo https://orcid.org/0000-0003-1353-2607
Park, Se Ho(박세호) ORCID logo https://orcid.org/0000-0001-8089-2755
Park, Hyung Seok(박형석) ORCID logo https://orcid.org/0000-0001-5322-6036
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
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