PMID- 16514409
OWN - NLM
STAT- MEDLINE
DCOM- 20060710
LR  - 20230210
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 19
IP  - 4
DP  - 2006 Apr
TI  - Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial 
      sarcoma.
PG  - 541-7
AB  - The prognosis of patients with synovial sarcomas is poor. New therapeutic 
      strategies, such as target inhibition of the tyrosine kinase activity of the 
      epidermal growth factor receptor (EGFR) with erlotinib and gefinitib, could be 
      effective, because most synovial sarcomas overexpress this protein. In lung 
      cancer, the responsiveness to gefinitib is strongly related to the presence of 
      mutations in the tyrosine kinase domain of the EGFR gene, while erlotinib 
      sensitivity seems to be partly linked to chromosome 7 polysomy or gene 
      amplification. To clarify the role of EGFR in synovial sarcoma and to explore the 
      potential for a targeted therapy approach, we have examined 13 of these soft 
      tissue tumors. We have analyzed the EGFR expression by immunohistochemistry, 
      searched for polysomy and gene amplification with fluorescence in situ 
      hybridization (FISH) and screened for EGFR mutations in exons 18-21 using PCR and 
      direct sequencing. All 13 tumors showed strong diffuse or focal EGFR expression. 
      No amplifications of the EGFR gene were found. In contrast, several point 
      mutations were identified in exons 18-21 of two synovial sarcomas. Whereas one of 
      these tumors carried only a synonymous mutation, two missense mutations in exons 
      19 and 21 of the EGFR gene (P733S and A840 T, respectively) could be demonstrated 
      in the second sample. In conclusion, strong EGFR expression in synovial sarcomas 
      is not related to gene amplification. The existence of mutations in the tyrosine 
      kinase domain of the EGFR gene in a small subset of synovial sarcomas suggests 
      that only few patients may profit from the tyrosine kinase inhibitor therapy.
FAU - Bode, Beata
AU  - Bode B
AD  - Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. 
      beata.bode@usz.ch
FAU - Frigerio, Simona
AU  - Frigerio S
FAU - Behnke, Silvia
AU  - Behnke S
FAU - Senn, Belinda
AU  - Senn B
FAU - Odermatt, Bernhard
AU  - Odermatt B
FAU - Zimmermann, Dieter R
AU  - Zimmermann DR
FAU - Moch, Holger
AU  - Moch H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - DNA Mutational Analysis
MH  - ErbB Receptors/analysis/*genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Mutation, Missense
MH  - Point Mutation
MH  - Protein-Tyrosine Kinases/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoma, Synovial/genetics/metabolism/*pathology
EDAT- 2006/03/04 09:00
MHDA- 2006/07/13 09:00
CRDT- 2006/03/04 09:00
PHST- 2006/03/04 09:00 [pubmed]
PHST- 2006/07/13 09:00 [medline]
PHST- 2006/03/04 09:00 [entrez]
AID - S0893-3952(22)03383-X [pii]
AID - 10.1038/modpathol.3800560 [doi]
PST - ppublish
SO  - Mod Pathol. 2006 Apr;19(4):541-7. doi: 10.1038/modpathol.3800560.