KIT and PDGFRalpha mutational analyses of mixed cell-type gastrointestinal stromal tumours

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.

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.

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.