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Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study

Authors
 Jae Seok Lee  ;  Sun Min Lim  ;  Sun Young Rha  ;  Jae Kyung Roh  ;  Yong Jin Cho  ;  Kyu Ho Shin  ;  Woo Ik Yang  ;  Se Hoon Kim  ;  Hyo Song Kim 
Citation
 Journal of Clinical Pathology, Vol.67(1) : 33-39, 2014 
Journal Title
 Journal of Clinical Pathology 
ISSN
 0021-9746 
Issue Date
2014
Abstract
BACKGROUND: We investigated the diagnostic and prognostic usefulness of anaplastic lymphoma kinase (ALK) expression in Asian rhabdomyosarcoma (RMS) patients. PATIENTS AND METHODS: A total of 38 RMS tissue samples were collected over a 14-year period (1998-2012). ALK protein expression and gene copy number were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). RESULTS: Ten of the 38 RMS patients (26.3%) showed positive ALK protein expression. ALK protein expression was predominantly positive in alveolar RMS (ARMS) compared with embryonal RMS (ERMS) (80% vs 20%, p=0.03). ALK protein expression was statistically associated with ARMS histology, metastatic disease at diagnosis, and primary trunk site. In FISH analysis, no translocations were detected and ALK gene copy number gain was observed more frequently in ARMS than in ERMS (40% vs 17%). The ALK-positive group showed inferior overall survival (OS) compared with ALK-negative group (p=0.014) for both alveolar and embryonal RMS patients. In multivariate analysis, positive ALK expression was an independent prognostic factor for OS (p=0.02; HR, 3.1; 95% CI 1.2 to 8.3). There was a significant strong positive correlation between ALK gene copy number and protein expression (Spearman's r<0.001, r=0.77). CONCLUSIONS: We demonstrated that ALK protein expression is statistically associated with ARMS histology, metastatic disease at diagnosis and primary trunk site. Additionally, ALK expression was an independent prognostic factor for worse survival. There was a strong correlation between IHC and FISH. Further studies are needed to evaluate the potential diagnostic and therapeutic role of ALK expression in RMS.
Full Text
http://jcp.bmj.com/content/67/1/33.long
DOI
10.1136/jclinpath-2013-201655
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
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
Yonsei Authors
김세훈(Kim, Se Hoon) ORCID logo https://orcid.org/0000-0001-7516-7372
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
노재경(Roh, Jae Kyung)
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
신규호(Shin, Kyoo Ho)
양우익(Yang, Woo Ick) ORCID logo https://orcid.org/0000-0002-6084-5019
이재석(Lee, Jae Seok)
임선민(Lim, Sun Min)
조영진(Cho, Yong Jin)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98172
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