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.
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 RMSpatients. 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.
Authors: Min Hwan Kim; Soohyeon Lee; Ja Seung Koo; Kyung Hae Jung; In Hae Park; Joon Jeong; Seung Il Kim; Seho Park; Hyung Seok Park; Byeong-Woo Park; Joo-Hang Kim; Joohyuk Sohn Journal: PLoS One Date: 2015-03-24 Impact factor: 3.240
Authors: Vijaykumar R Holla; Yasir Y Elamin; Ann Marie Bailey; Amber M Johnson; Beate C Litzenburger; Yekaterina B Khotskaya; Nora S Sanchez; Jia Zeng; Md Abu Shufean; Kenna R Shaw; John Mendelsohn; Gordon B Mills; Funda Meric-Bernstam; George R Simon Journal: Cold Spring Harb Mol Case Stud Date: 2017-01
Authors: Anke E M van Erp; Melissa H S Hillebrandt-Roeffen; Laurens van Houdt; Emmy D G Fleuren; Winette T A van der Graaf; Yvonne M H Versleijen-Jonkers Journal: Target Oncol Date: 2017-12 Impact factor: 4.493
Authors: Joaquim Bellmunt; Shamini Selvarajah; Scott Rodig; Marta Salido; Silvia de Muga; Irmgard Costa; Beatriz Bellosillo; Lillian Werner; Stephanie Mullane; André P Fay; Robert O'Brien; Jordi Barretina; André E Minoche; Sabina Signoretti; Clara Montagut; Heinz Himmelbauer; David M Berman; Philip Kantoff; Toni K Choueiri; Jonathan E Rosenberg Journal: PLoS One Date: 2014-08-01 Impact factor: 3.240