GISTの臨床病理学的特徴と遺伝子異常

Clinicopathological Features and Oncogene Mutation in GIST

要旨　胃腸管間質細胞腫瘍（GIST）は消化管に発生する間葉系腫瘍で最も多く，その大半はKIT蛋白を発現する．高頻度にKIT遺伝子異常を有し，少数例ではPDGFRA変異を有する．これまでの研究で，KIT/PDGFRA変異亜型は，GISTの発生部位，細胞型，KIT蛋白発現，予後と相関があることがわかってきた．また，消化管外にもGIST同様の組織像，KIT/PDGFRA遺伝子異常を有する腫瘍が存在することも明らかとなった．KIT蛋白をターゲットとした分子標的治療薬も開発され一定の効果がみられるが，今後はさらに個々の臨床病理学的特徴や遺伝子異常に応じた治療が期待される．

　Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. And it is typically characterized by immunohistochemical expression of c-kit (KIT). Several studies have revealed various types of KIT oncogene mutations. PDGFRA gene mutations have also been found in a minor subset of GIST. Moreover, recent studies have revealed that some types of mutations are associated with clinicopathological features such as tumor location, cell type, KIT expression and prognosis in patients with GIST. We have found frequent KIT and PDGFRA mutations of GIST in extra-gastrointestinal sites (EGIST). Although imatinib (Glivec^®), a tyrosine kinase inhibitor, is an effective therapy for GIST, tailored molecular-targeted therapy based on individual clinicopathological and genotypic features can be expected in future.