PMID- 25803816 OWN - NLM STAT- MEDLINE DCOM- 20160225 LR - 20200306 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC): prevalence, clinicopathologic features and prognostic implication. PG - e0120320 LID - 10.1371/journal.pone.0120320 [doi] LID - e0120320 AB - 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. FAU - Kim, Min Hwan AU - Kim MH AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. FAU - Lee, Soohyeon AU - Lee S AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. FAU - Koo, Ja Seung AU - Koo JS AD - Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. FAU - Jung, Kyung Hae AU - Jung KH AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Park, In Hae AU - Park IH AD - Center for Breast Cancer, National Cancer Center, Goyang, Korea; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. FAU - Jeong, Joon AU - Jeong J AD - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Seung Il AU - Kim SI AD - Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. FAU - Park, Seho AU - Park S AD - Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. FAU - Park, Hyung Seok AU - Park HS AD - Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. FAU - Park, Byeong-Woo AU - Park BW AD - Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Joo-Hang AU - Kim JH AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. FAU - Sohn, Joohyuk AU - Sohn J AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. LA - eng PT - Clinical Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150324 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adult MH - Aged MH - Anaplastic Lymphoma Kinase MH - Breast/*pathology MH - Female MH - *Gene Amplification MH - *Gene Dosage MH - Humans MH - Inflammatory Breast Neoplasms/diagnosis/epidemiology/*genetics MH - Middle Aged MH - Prognosis MH - Proportional Hazards Models MH - Receptor Protein-Tyrosine Kinases/analysis/*genetics MH - Republic of Korea/epidemiology MH - Retrospective Studies MH - Survival Analysis MH - Triple Negative Breast Neoplasms/diagnosis/epidemiology/genetics PMC - PMC4372579 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/03/25 06:00 MHDA- 2016/02/26 06:00 PMCR- 2015/03/24 CRDT- 2015/03/25 06:00 PHST- 2014/11/23 00:00 [received] PHST- 2015/02/06 00:00 [accepted] PHST- 2015/03/25 06:00 [entrez] PHST- 2015/03/25 06:00 [pubmed] PHST- 2016/02/26 06:00 [medline] PHST- 2015/03/24 00:00 [pmc-release] AID - PONE-D-14-51829 [pii] AID - 10.1371/journal.pone.0120320 [doi] PST - epublish SO - PLoS One. 2015 Mar 24;10(3):e0120320. doi: 10.1371/journal.pone.0120320. eCollection 2015.