PDGFRα- and c-kit-mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features

Aims: To study the immunohistochemical and histological features of 158 gastrointestinal stromal tumours (GISTs), consisting of 137 tumours with mutations in c-kit and platelet-derived growth factor receptor-alpha (PDGFRalpha) genes and 21 wt-GISTs. Additionally, we evaluated the localization of PDGFRalpha in the normal intestine. PDGFRalpha gene mutations were recently described in a subset of GISTs and it has been hypothesized that PDGFRalpha-mutated tumours represent a distinctive entity among GISTs. Results: PDGFRalpha was expressed in ganglion bodies of the myenteric plexus and in Schwann cells but not in interstitial cells of Cajal. In contrast to other GISTs, tumours with PDGFRalpha mutations had an epithelioid phenotype and multinuclear giant cells. Kit was down-regulated in PDGFRalpha-mutated GISTs and PDGFRalpha expression was decreased in c-kit mutated tumours. Dot-like staining of Kit and PDGFRalpha was associated very frequently with mutation within the respective gene. Conclusions: Features of PDGFRalpha-mutated GISTs are multinuclear giant cells and dot-like staining for PDGFRalpha. In contrast, c-kit-mutated GISTs display a spindle cell phenotype and Kit-dots on immunohistochemistry. Our findings not only help to distinguish distinctive entities of GISTs using histological and immunhistochemical features, but also indicate that Kit and PDGFRalpha are differentially regulated in a subset of GISTs.