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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
MeSH
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis* ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Child ; Child, Preschool ; Female ; Gene Dosage ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Infant ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases/genetics* ; Receptor Protein-Tyrosine Kinases/metabolism ; Rhabdomyosarcoma/genetics* ; Rhabdomyosarcoma/mortality* ; Rhabdomyosarcoma/pathology ; Young Adult
Keywords
FISH ; IMMUNOCYTOCHEMISTRY ; rhabdomyosarcoma
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 Internal Medicine (내과학교실) > 1. Journal Papers
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
Yonsei Authors
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Roh, Jae Kyung(노재경)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shin, Kyoo Ho(신규호)
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Lee, Jae Seok(이재석)
Lim, Sun Min(임선민)
Cho, Yong Jin(조용진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98172
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