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

Jae Seok Lee, Sun Min Lim, SunYoung Rha, Jae Kyung Roh, Yong Jin Cho, Kyu Ho Shin, Woo Ik Yang, SeHoon Kim, Hyo Song Kim

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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.

Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalJournal of Clinical Pathology
Volume67
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Rhabdomyosarcoma
Fluorescence In Situ Hybridization
Genes
Gene Dosage
Alveolar Rhabdomyosarcoma
Embryonal Rhabdomyosarcoma
Proteins
anaplastic lymphoma kinase
Survival
Histology
Immunohistochemistry
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Lee, Jae Seok ; Lim, Sun Min ; Rha, SunYoung ; Roh, Jae Kyung ; Cho, Yong Jin ; Shin, Kyu Ho ; Yang, Woo Ik ; Kim, SeHoon ; Kim, Hyo Song. / Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study. In: Journal of Clinical Pathology. 2014 ; Vol. 67, No. 1. pp. 33-39.
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title = "Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study",
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.",
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Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study. / Lee, Jae Seok; Lim, Sun Min; Rha, SunYoung; Roh, Jae Kyung; Cho, Yong Jin; Shin, Kyu Ho; Yang, Woo Ik; Kim, SeHoon; Kim, Hyo Song.

In: Journal of Clinical Pathology, Vol. 67, No. 1, 01.01.2014, p. 33-39.

Research output: Contribution to journalArticle

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T1 - Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study

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AU - Lim, Sun Min

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AU - Roh, Jae Kyung

AU - Cho, Yong Jin

AU - Shin, Kyu Ho

AU - Yang, Woo Ik

AU - Kim, SeHoon

AU - Kim, Hyo Song

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N2 - 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.

AB - 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.

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