Activating <i>PDGFRA</i> mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are associated with tumour localization

Abstract

Huss S, Wardelmann E, Goltz D, Binot E, Hartmann W, Merkelbach‐Bruse S, Büttner R &amp; Schildhaus H‐U (2012) Histopathology 61, 59–68 Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are associated with tumour localization Aims: Inflammatory fibroid polyps (IFP) are mesenchymal tumours of the gastrointestinal tract. This study was performed to broaden the base of evidence of the pathogenic role of PDGFR mutations in IFP with particular regard to clinicopathological data and mutational patterns among IFP subtypes. Methods and results: Molecular analysis of 38 tumours revealed activating mutations in three different exons of PDGFRA in 25 IFP. For the first time we report two cases with PDGFRA ‐exon 14 mutations (p.N659K; p.[N659K(+)T665A]). The results of our study and cases reported earlier indicate clearly that there is a localization‐specific pattern: exon 12 mutations predominate in the small intestine, while exon 18 mutations occur frequently in the stomach ( P &lt; 0.001). Codons 567–571 of PDGFRA represent an IFP specific mutational hot spot and are affected most frequently by deletions. Furthermore, in our series IFP of the stomach share common features. In contrast to intestinal IFP, gastric tumours occur at higher age, show heavy inflammation and tend to be smaller. IFP located in the small intestine are frequently associated with intussusception. Conclusion: We conclude that there is a ‘small bowel’ and a ‘gastric’ phenotype of IFPs which are associated with exon 12 and exon 18 PDGFRA mutations, respectively.