Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study.
BACKGROUND
We investigated the diagnostic and prognostic usefulness of anaplastic lymphoma kinase (ALK) expression in Asian rhabdomyosarcoma (RMS) patients.


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.
Department of Pathology, Yonsei University College of Medicine, , Seoul, Korea.
Jae Seok
JS
Lee
Sun Min
SM
Lim
Sun Young
SY
Rha
Jae Kyung
JK
Roh
Yong Jin
YJ
Cho
Kyu Ho
KH
Shin
Woo Ik
WI
Yang
Se Hoon
SH
Kim
Hyo Song
HS
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D055815:Young Adult
D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
FISH; IMMUNOCYTOCHEMISTRY; rhabdomyosarcoma