消化管GISTの診断と悪性度の評価―分子病理学的因子からみて

Advanced Studies of Risk Categories Involved in Gastrointestinal Stromal Tumor (GIST)

要旨　gastrointestinal stromal tumor（GIST）の大部分は，c-kitもしくはplatelet-derived growth factor receptor（PDGFR）αの機能獲得型変異によって発生することが解明されて以来，その診断・治療・予後に関する概念・戦略も大きく変化した．そのためGISTの悪性度評価も，形態組織学的方法から進んで，種々の分子病理学的方法を用いた検討に期待が寄せられるようになってきた．本稿では，分子病理学的因子からみたGISTの悪性度評価を検討した最近の知見から，細胞増殖関連抗原，細胞周期蛋白，c-kitとPDGFRα遺伝子異常，およびそのほかの遺伝子異常について概説する．

　Mutually exclusive gain-of-function c-kit and PDGFRα mutations occur in the majority of gastrointestinal stromal tumors (GIST). According to a drastic change in the concept of GIST, the concept and strategies of diagnosis, treatment and prognosis of this tumor have also been changed. At present, tumor size and mitotic activity are the best predictive prognostic features, but risk categories of this tumor, based on molecular pathological analysis, have been under investigation. This review summarizes updated studies concerning risk categories based on the Ki-67 proliferation index, abnormalities in cell cycle regulators, c-kit and PDGFRα mutations, and other molecular pathological and cytogenetic alterations which predict the biological behavior of GIST.