KIT and PDGFRalpha mutational analyses of mixed cell-type gastrointestinal stromal tumours.
OBJECTIVE
To determine whether the epithelioid and spindle components of a mixed cell-type gastrointestinal stromal tumour (GIST) show the same receptor tyrosine kinase mutation and, by inference, the same sensitivity to imatinib.


RESULTS
Six mixed cell-type GISTs were identified from 108 gastric GISTs. Clinicopathological and immunohistochemical data of the six neoplasms were collated. For each neoplasm, DNA was extracted separately from the laser-microdissected epithelioid and spindle components and non-neoplastic tissue and sequenced for KIT and platelet-derived growth factor receptor (PDGFR)alpha mutations. The epithelioid component often showed less CD117 and/or CD34 immunoreactivity than the spindle component of the same mixed cell-type GIST. Four mixed cell-type GISTs showed somatic KIT mutations (deletions in exon 11 in three tumours and an insertion in exon 9 in one tumour) and one showed a somatic PDGFRalpha mutation (point mutation in exon 18); in each of the five cases, both epithelioid and spindle components showed identical mutations.


CONCLUSIONS
The presence of the same receptor tyrosine kinase mutation in both components of a mixed cell-type GIST suggests that both components should be equally responsive to imatinib treatment, and that such mutation is an early key event in the pathogenesis of these neoplasms.
Department of Histopathology, Bristol Royal Infirmary, Bristol, UK. nacs.wong@bristol.ac.uk
N A C S
NA
Wong
S
S
Mangwana
D000368:Aged; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
D017931:DNA Primers; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha