title: Strong PDGFRA positivity is seen in GISTs but not in other intra-abdominal mesenchymal tumors: Immunohistochemical and mutational analyses.
abstract: Mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene has been well documented as an alternative oncogenic mechanism in a subset of gastrointestinal stromal tumors (GISTs) lacking c-kit mutations. However, the role of PDGFRA immunohistochemistry in the diagnosis of GISTs has not been well studied. We investigated PDGFRA immunoreactivity in GISTs and in other intra-abdominal mesenchymal tumors, and correlated PDGFRA expression with CD117 positivity and with the mutational status of PDGFRA and c-kit genes. In addition, expression of phosphorylated AKT, an activated downstream molecule in the PDGFRA and c-kit signaling pathways, was correlated with PDGFRA and CD117 status. A total of 39 GISTs and 20 other mesenchymal tumors in the abdomen were included in this study. Thirty-five of 39 GIST cases (89.7%) were positive for PDGFRA and 19 of these 35 positive cases were strongly positive. Five of 20 non-GIST lesions (25%) were positive for PDGFRA, but none of these cases were strongly positive. With one exception, PDGFRA-positive cases were also positive for CD117. Phosphorylated AKT positivity was not associated with the immunoreactivity or mutation of PDGFRA and c-kit, suggesting that the activation of AKT is probably independent of the activation of PDGFRA and c-kit in GISTs. Of 14 GISTs assayed, 4 had mutations in c-kit at exons 11 or 17, and 4 had mutations in PDGFRA at exons 12 or 18. Three of 4 GIST cases with PDGFRA mutations show epithelioid morphology and strong PDGFRA immunoreactivity with prominent perinuclear dotlike accentuation (so-called Golgi pattern). In conclusion, strong PDGFRA positivity with Golgi pattern is a useful adjunct in the diagnosis of GISTs with PDGFRA mutation.
authors.affiliation: Department of Pathology, University of California San Diego, San Diego, CA 92103-8720, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Peterson
authors.forename: Zhe
authors.initials: Z
authors.lastname: Piao
authors.forename: Noel
authors.initials: N
authors.lastname: Weidner
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
mesh_terms: D000008:Abdominal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005350:Fibroma / Q000378:metabolism / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009442:Neurilemmoma / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D009418:S100 Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D051058:Oncogene Protein v-akt