PURPOSE: The aim of this study is to investigate anaplastic lymphoma kinase 
(ALK) protein expression and underlying genetic aberrations in rhabdomyosarcoma 
(RMS), with special attention to clinical and prognostic implications.
PATIENTS AND METHODS: A total of 189 paraffin-embedded RMS tumor specimens from 
145 patients were collected on tissue microarray. ALK protein expression was 
evaluated by immunohistochemistry. ALK gene (2p23) copy number and 
translocations were determined by in situ hybridization. cDNA sequencing of the 
receptor tyrosine kinase domain of the ALK gene was assessed in 43 samples.
RESULTS: Strong cytoplasmic ALK protein expression was more frequently observed 
in alveolar RMS (ARMS) than in embryonal RMS (ERMS) (81% v 32%, respectively; P 
< .001). ALK gene copy number gain was detected in the vast majority of ARMS 
(88%), compared with 52% of ERMS (P < .001). ALK copy number correlated with 
protein expression in primary tumors (n = 107). We identified one point mutation 
(2%) and seven tumors harboring whole exon deletions (16%). In ERMS, specific 
ALK gain in the primary tumor correlated with metastatic disease (100% in 
metastatic disease v 29% in nonmetastatic disease; P = .004) and poor 
disease-specific survival (5-year disease-specific survival: 62% v 82% for 
nonspecific or no gain; P = .046).
CONCLUSION: Because ALK aberrations on genomic and protein levels are frequently 
found in RMSs, in particular ARMS, and are associated with disease progression 
and outcome in ERMS, ALK may play a role in tumor biology and may provide a 
potential therapeutic target for these tumors. Future research should aim at the 
oncogenic role of ALK and the potential effect of ALK inhibitors in RMS.