细胞周期蛋白D1、Ki-67和bcl-2的表达与CD117阳性的胃肠道间质瘤生物学行为的关系

Relationship between expression of cyclin D1, Ki-67 and bcl-2 and biologic behavior in CD117-positive gastrointestinal stromal tumors

目的检测细胞周期蛋白D1(cyclin D1)、Ki-67和bcl-2在胃肠道间质瘤(GIST)中的表达,探讨它们在GIST发生、发展中的作用及临床病理意义.方法 59例手术切除GIST标本进行CD117、CD34、平滑肌肌动蛋白(SMA)、结蛋白、S-100、cyclin D1、bcl-2和Ki-67免疫组织化学染色,同时进行病理形态学观察包括形态学类型、肿瘤大小、坏死和核分裂象.所有病例随访2～9年.所有数据进行单因素、多因素和相关分析.结果随访40例患者一直健在,15例患者死于GIST,4例患者死于其他原因.统计学分析显示肿瘤直径>5 cm、有坏死、核分裂象在每50个高倍视野>5个、Ki-67增殖指数(LI)>5%、cyclin D1和bcl-2免疫组织化学染色强阳性都可以作GIST患者手术后的预测指标,且具有统计学意义;核分裂象和Ki-67增殖指数是独立的预测指标;Ki-67 LI≥5%和核分裂象≥5/50 HPF呈正相关(r=0.532,P<0.01 );cyclin D1与bcl-2强阳性表达呈正相关(r=0.273,P<0.05).结论肿瘤大小、坏死、核分裂象、cyclin D1、Ki-67增殖指数和bcl-2可作为GIST患者临床预测指标;核分裂象和Ki-67增殖指数可作为独立的预测指标;cyclin D1 与bcl-2呈明显相关性, Ki-67免疫组织化学染色可以代替核分裂象作为一项很有用的预测指标.

Objective To investigate the clinicopathologic features of gastrointestinal stromal tumors （GISTs） and to identify reliable prognostic parameters. Methods Fifty-nine GISTs were studied by immunostaining of CD117, CD34, SMA, desmin, S-100, bcl-2, and Ki-67. Histopathologic evaluations included tumor size, necrosis, histological growth patterns, mitotic activities and tumor lymphocytic infiltrate. The patients were clinically followed for 2 to 9 years. Univariate, multivariate and correlative statistical evaluations were used to analyze the data. Results Among the 59 patients, 40 were alive and 15 died of their tumors at follow-up, the remaining 4 patients died of other causes. Pathological parameters that correlated with prognosis included tumor sizes of more than 5 cm, tumor tissue necrosis, mitotic cell count equal or higher than 5 per 50 high power field, Ki-67 labeling index （LI）equal or higher than 5% and intense bcl-2 immunostaining. Multivariate analysis showed that the mitotic count and Ki-67 LI were independent prognostic indicators. There was a correlation between mitotic count and Ki-67 LI. Conclusions Mitotic count and Ki-67 LI are the best predictors for a poor outcome of GIST after surgical treatment. Ki-67 immunostaining may substitute mitotic count as a useful prognostic parameter.