Aims: To investigate the value of platelet-derived growth factor receptors (PDGFRs) by immunohistochemistry in discriminating KIT-negative gastrointestinal stromal tumours (GISTs) from other soft-tissue neoplasms of the digestive tract. Methods and results: One-hundred and sixty-seven primary gastrointestinal mesenchymal tumours (125 GISTs, 15 intra-abdominal desmoids, 12 leiomyomas, eight leiomyosarcomas, three schwannomas, two solitary fibrous tumours, and one case each of inflammatory pseudotumour and fibroid polyp) were reclassified based on morphology and on the immunohistochemical panel recommended by the National Institutes of Health consensus on GIST. All cases were then tested with antibodies specific for PDGFR a and b. Of 125 GISTs, 117 were KIT-positive (93.6%) and eight KIT-negative (6.4%). All the KIT-positive GISTs were negative for both PDGFRs, while all the eight KIT-negative GISTs expressed PDGFR-a, with two of them also coexpressing PDGFR-b. Among the 42 non-GIST tumours, only a small percentage (26.6%) of desmoids immunostained for PDGFR-a, two of them coexpressing PDGFR-b. Conclusions: Immunostaining with PDGFR-a is a helpful marker in discriminating between KIT-negative GISTs and other gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for PDFGR-a, while none of the other gastrointestinal mesenchymal tumours analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These preliminary data demonstrate the suitability of commercially available antibodies to detect immunohistochemically the mutually exclusive expression of KIT and PDGFR-a previously reported in GISTs by molecular biological techniques. Since PDGFR exists in the form of a homodimer (aa, bb) or heterodimer (ab) and two of the KIT-negative GISTs coexpressed both PDGFR isoforms, further investigations are required to elucidate the role of PDGFR-b in GISTs.

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