PMID- 18788887
OWN - NLM
STAT- MEDLINE
DCOM- 20091117
LR  - 20181201
IS  - 1093-5266 (Print)
IS  - 1093-5266 (Linking)
VI  - 12
IP  - 4
DP  - 2009 Jul-Aug
TI  - ALK expression in rhabdomyosarcomas: correlation with histologic subtype and 
      fusion status.
PG  - 275-83
LID - 10.2350/08-03-0434.1 [doi]
AB  - Immunohistochemical staining for anaplastic lymphoma kinase (ALK) has been 
      described in rhabdomyosarcomas (RMS), especially the alveolar subtype. Previous 
      studies have yielded conflicting results regarding the pattern of staining 
      (nuclear versus cytoplasmic), and there has been no correlation with PAX3-7/FKHR 
      fusion status. This study was undertaken to evaluate ALK receptor protein 
      expression in a large series of RMS; to correlate these results with fusion 
      status; and to investigate the possibility of 2p23 amplification or translocation 
      using fluorescence in situ hybridization (FISH). Sixty-nine cases of RMS were 
      examined and classified as alveolar RMS (ARMS), embryonal RMS (ERMS), or 
      unclassifiable RMS (URMS) subtypes. Anaplastic lymphoma kinase 
      immunohistochemistry was performed using anti-human CD246 antibody; cases were 
      considered positive when more than 50% of cells had moderate or intense 
      cytoplasmic and/or nuclear staining. There were 30 ARMS, 37 ERMS, and 2 URMS 
      subtypes. Reverse transcription-polymerase chain reaction for PAX3/PAX7-FKHR 
      fusion analysis had been done in all cases of ARMS, in 27 of 37 cases of ERMS, 
      and in both URMS cases. Anaplastic lymphoma kinase staining was positive in 16 of 
      30 ARMS (53%) and 9 of 39 nonalveolar RMS (23%) cases (P < 0.05). Of the 21 ARMS 
      cases with PAX3-FKHR fusion, 10 of 21 (48%) were positive for ALK staining; of 
      the 6 ARMS cases with PAX7-FKHR fusion, 3 of 6 (50%) were positive for ALK 
      staining; and 3 of 3 (100%) of the fusion-negative ARMS were positive with ALK 
      staining. When comparing each of the ARMS subtypes, statistical significance was 
      not reached. All positive cases showed dot-like cytoplasmic staining; nuclear 
      staining was not seen. Of a subset of 6 ALK-positive ARMS submitted for 
      break-apart FISH for the ALK locus, there was no evidence of a translocation; 1 
      case had ALK amplification and 2 had low-level gains of the ALK gene. We conclude 
      that there is ALK overexpression in RMS, more commonly in ARMS than in ERMS, most 
      likely independent of fusion status. Amplification or upregulation of ALK may 
      underlie ALK protein overexpression.
FAU - Corao, Diana A
AU  - Corao DA
AD  - Department of Pathology, A. I. DuPont Hospital for Children, Wilmington, DE, USA. 
      dcorao@nemours.org
FAU - Biegel, Jaclyn A
AU  - Biegel JA
FAU - Coffin, Cheryl M
AU  - Coffin CM
FAU - Barr, Frederic G
AU  - Barr FG
FAU - Wainwright, Luanne M
AU  - Wainwright LM
FAU - Ernst, Linda M
AU  - Ernst LM
FAU - Choi, John K
AU  - Choi JK
FAU - Zhang, Paul J
AU  - Zhang PJ
FAU - Pawel, Bruce R
AU  - Pawel BR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pediatr Dev Pathol
JT  - Pediatric and developmental pathology : the official journal of the Society for 
      Pediatric Pathology and the Paediatric Pathology Society
JID - 9809673
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (PAX3-FKHR fusion protein, human)
RN  - 0 (PAX7 Transcription Factor)
RN  - 0 (PAX7 protein, human)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adolescent
MH  - Anaplastic Lymphoma Kinase
MH  - Biomarkers, Tumor/analysis
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Oncogene Proteins, Fusion/genetics
MH  - PAX7 Transcription Factor/genetics
MH  - Protein-Tyrosine Kinases/*biosynthesis
MH  - Receptor Protein-Tyrosine Kinases
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Rhabdomyosarcoma, Alveolar/*genetics/*pathology
MH  - Rhabdomyosarcoma, Embryonal/*genetics/*pathology
EDAT- 2008/09/16 09:00
MHDA- 2009/11/18 06:00
CRDT- 2008/09/16 09:00
PHST- 2008/09/16 09:00 [pubmed]
PHST- 2009/11/18 06:00 [medline]
PHST- 2008/09/16 09:00 [entrez]
AID - 08-03-0434 [pii]
AID - 10.2350/08-03-0434.1 [doi]
PST - ppublish
SO  - Pediatr Dev Pathol. 2009 Jul-Aug;12(4):275-83. doi: 10.2350/08-03-0434.1.