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

• Published in: PloS one 2015-03, Vol.10 (3), p.e0120320
• Main Authors: Kim, Min Hwan, Lee, Soohyeon, Koo, Ja Seung, Jung, Kyung Hae, Park, In Hae, Jeong, Joon, Kim, Seung Il, Park, Seho, Park, Hyung Seok, Park, Byeong-Woo, Kim, Joo-Hang, Sohn, Joohyuk
• Format: Article
• Language: English
• Subjects: Adult; Aged; ALK protein; Analysis; Anaplastic Lymphoma Kinase; Breast - pathology; Breast cancer; Cancer; Cancer therapies; Chemotherapy; Copy number; ErbB-2 protein; Female; Fluorescence; Fluorescence in situ hybridization; Formaldehyde; Gene Amplification; Gene Dosage; Gene rearrangement; Genes; Genetic aspects; Hospitals; Humans; Inflammation; Inflammatory Breast Neoplasms - diagnosis; Inflammatory Breast Neoplasms - epidemiology; Inflammatory Breast Neoplasms - genetics; Internal medicine; Kinases; Lung cancer; Lymphoma; Lymphomas; Medical prognosis; Medical records; Medicine; Metastasis; Middle Aged; Molecular chains; Mutation; Neuroblastoma; Non-Hodgkin's lymphomas; Oncology; Paraffin; Pathogenesis; Patients; Prevalence studies (Epidemiology); Prognosis; Proportional Hazards Models; Protein-tyrosine kinase; Receptor Protein-Tyrosine Kinases - analysis; Receptor Protein-Tyrosine Kinases - genetics; Regression analysis; Republic of Korea - epidemiology; Retrospective Studies; Surgery; Survival; Survival Analysis; Triple Negative Breast Neoplasms - diagnosis; Triple Negative Breast Neoplasms - epidemiology; Triple Negative Breast Neoplasms - genetics; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120320

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