胰岛素样生长因子1受体在胃肠道间质瘤中的表达及其预后的意义

Ciinicopathological and prognostic analysis of insulin like growth factor 1 receptor protein expression in primary gastrointestinal stromal tumors

目的探讨胰岛素样生长因子1受体（insulin like growth factor 1 receptor，IGF1R）蛋白表达的特点与胃肠道间质瘤（gastrointestinal stromal tumors，GIST）患者的临床病理特征及预后的关系。方法回顾性分析2005年1月至2011年1月在江苏省苏北人民医院胃肠外科手术治疗的84例GIST患者的临床病理及生存资料。应用免疫组织化学方法检测IGF1R蛋白表达水平，并分析其与GIST患者的临床病理特征和无复发生存率的关系。结果GIST组中IGF1R蛋白阴性、弱阳性、阳性、强阳性表达率分别为20％、14％、48％和18％，对照组中IGF1R蛋白阴性、弱阳性、阳性、强阳性表达率分别为32％、40％、20％和8％，两组比较差异具有统计学意义（Х^2=30．663，P〈0．001）。本组患者的5年总生存率为93％，1年、3年和5年无复发生存率分别为99％、76％和60％。单因素生存分析结果显示，肿瘤原发部位（P=0．017）、肿瘤大小（P=0．022）、核分裂象计数（P〈0．001）、肿瘤黏膜浸润（P=0．003）、周围组织浸润（P=0．030）、肿瘤破裂（P=0．013）、NIH风险分级（P〈0．001）及IGF1R蛋白高表达（P=0．022）均与GIST患者的无病生存率有关。多因素生存分析结果显示，肿瘤大小（P=0．009）和核分裂象计数（P=0．015）是影响GIST患者术后无病生存率的独立危险因素。结论IGF1R蛋白水平的表达升高与GIST的发生、发展及不良预后有关。肿瘤大小和核分裂象计数是原发性GIST患者预后的独立危险因素。

Objective To investigate the clinicopathological significance of expression of insulin like growth factor 1 receptor （IGF1 R） protein in primary gastrointestinal stromal tumors （GIST） and their impacts on prognosis. Methods Between January, 2005 and January, 2011, 84 primary GIST patients underwent surgery. Immunohistoehemical analysis was performed based on tissue microarray to estimate expression pattern of IGF1R in tumor cells and normal controls. Association of IGF1R expression with clinicopathological features and relapse-free survival （RFS） were also analyzed. Results The negative, weakly positive, positive, and strong positive expression rates of IGF1R protein in GIST group were 20% , 14% ,48% and 18% , respectively; while in the control group were 32% ,40% ,20% and 8%, respectively （Х^2 =30. 663, P 〈0. 001 ）. The 5-year overall survival （OS） rate was 93%. 1-year, 3-year and 5-year RFS rate were 99% , 76% and 60% , respectively. As shown by univariate analysis the following factors were poor prognostic indicators for RFS, non-gastric tumor location （P = 0. 017） , large tumor size （P = 0. 022）, high mitotic index （P 〈 0. 001 ）, high cellularity （P = 0. 012）, tumor rupture （P = 0. 013 ）, absent or low expression ofIGF1R （P =0.022）. Tumor size （HR5.1-10 cm vs≤5cm = 1.86, 95% CI： 0.67 -5.15; HR〉10cm vs≤5cm = 6. 71, 95% CI： 0.67 - 5. 15, overall P = 0.023）, and mitotic index （HR5.1-10/50 HPFs vs≤5/50 HPFs = 5.72, 95% CI： 2. 09 - 15.64; HR〉10/50 HPFs vs.≤5/50 HPFs = 3. 44, 95% CI： 1. 13 - 10.45, overall P = 0.002 ） were negative independent risk predictors by multivariate analysis. Conclusions High expression of IGF1R may be involved in the occurrence, development and poor prognostic of primary GIST. Expression of IGF1R is correlated with high risk potential and may predict early recurrence.