胃肠道间质瘤诊治的研究进展

Research progress on diagnosis and treatment of gastrointestinal stromal tumor

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是消化系统最常见的间叶源性肿瘤,起源于Cajal细胞或胃肠起搏细胞。其能够生长于胃肠道的任何部位,胃和小肠多见,其次为结直肠。GIST的发病机制与c-kit及血小板源性生长因子受体α(platelet-derived growth factor receptor-alpha,PDGFRA)的活化突变有关。GIST的临床表现无特征性,最终靠病理学确诊,而病理诊断取决于形态学和免疫组织化学结果。必要时可行基因学分析,其中CD117与DOG1的表达有助于特殊基因型GIST的诊断。目前GIST在治疗上以外科手术联合靶向治疗为主要方案,近年来随着新型手术器械的发展,腹腔镜手术也已逐渐得到人们的认可。伊马替尼是一种酪氨酸激酶抑制剂,能够特异性抑制kit、PDGFRA和bcl-al,于2001年批准使用。而舒尼替尼与伊马替尼比较而言,作用靶点更多,是GIST的二线药物,二者作用机理类似。以伊马替尼为代表的分子靶向药物在对GIST的治疗及改善患者预后中有显著疗效,在肿瘤的分子靶向治疗中代表着里程碑式的意义。但是随着用药时间的增长,GIST耐药逐渐成为影响GIST患者预后的重要因素之一。GIST的发病机制复杂,基因突变的种类多样,所以根据患者个体情况所制定的特定治疗方案更为重要。危险度分级被广泛应用于判断预后和指导分子生物靶向治疗。本文就胃肠道间质瘤现阶段的诊治与治疗研究进展作一综述。

Gastrointestinal stromal tumor （GIST） is the most common type of gastrointestinal mesenchymal tissue tumors, originated in Cajal cells or gastrointestinal pacing cells. It can grow in any part of the gastrointestinal tract, where the stomach and small intestine are multiple, followed by coloreetal. The pathogenesis of GIST is associated with activation of c-kit and platelet-derived growth factor receptor-alpha （PDGFRA）. Due to its lack of characteristic clinical manifesta- tions, the final diagnosis depends on pathology, and the pathologic diagnosis depends on morphological and immunohisto- chemical results. The feasible genetic analysis that tests the expression of CD117 and DOG1 will contribute to the diagno- sis of special genotype GIST if necessary. At present, surgery combined with targeted therapies is the popular solution for GIST. With the development of new surgical instruments, the laparoseopic surgery has also＇been gradually recognized by the people in recent years. Imatinib, as a tyrosine kinase inhibitor, can specifically inhibit the expression fo kit, PDG- FRA and bcl-al, it had been approved for use in 2001. Sunitinib, when compared with Imatinib, is with more targets, which is applied as the second-line drugs for GIST. The action mechanism of the two drugs is similar. Molecular targeting drugs, represented by Imatinib, is effective in the treatment of GIST and improving the prognosis of patients, which re- presents milestone significance in molecular targeted therapy of tumors. However, with the increase of drug time, GIST resistance gradually becomes one of the important factors affecting the prognosis of patients with GIST. The pathogenesis of GIST is complex and the variety of gene mutations is diverse, so it is more important to develop specific treatment regi- mens based on the individual patient＇ s condition. Risk grading is widely used to determine prognosis and to guide molec- ular bio-targeted therapy. In this paper, the progress of diagnosis and treatment of gastrointestinal stromal tumors at this stage is reviewed.