肿瘤相关巨噬细胞和 KIT 评估胰腺神经内分泌肿瘤肝转移及预后的价值

Tumor-associated macrophages and KIT predict liver metastasis of pancreatic neuroendocrine tumors and prognosis

目的：探讨肿瘤相关巨噬细胞（ TAMs）结合3型酪氨酸激酶受体（ KIT）对胰腺神经内分泌肿瘤（ PNETs）肝转移风险及预后的评估价值。方法收集1995年1月至2015年5月间中山大学孙逸仙纪念医院行手术治疗并经病理诊断证实的79例PNETs患者资料。采用免疫组化染色法检测肿瘤组织CD68、KIT蛋白表达，分析其与肿瘤临床病理参数的相关性。结果79例PNETs中30例（38．0％）瘤组织CD68高表达，35例（44．3％）瘤组织KIT高表达。 CD68高表达与肿瘤侵犯（P＜0．001）、AJCC7th分期（P＜0．001）、肝转移（P＜0．001）及其发生时间有关（P＝0．019）；CD68低表达患者的生存期显著长于高表达患者，差异有统计学意义（P＝0．0002）。 KIT高表达与WHO 2010及AJCC7th分期（P＜0．001， P＝0．002）、肿瘤无功能性（P＝0．002）、肝转移有关（P＝0．026）；KIT低表达患者的生存期显著长于高表达患者，差异有统计学意义（P＝0．0013）。 CD68、KIT均高表达患者常见于肿瘤侵犯者（P＜0．001），与WHO 2010、AJCC7th分期有关（ P值均＜0．001）；CD68、KIT均高表达患者的生存期显著短于均低表达者，差异有统计学意义（P＝0．0057）。多因素分析显示AJCC7th分期Ⅳ期、CD68高表达是PNETs患者预后的独立危险因素。结论 CD68、KIT高表达与PNETs分级分期、肝转移风险、不良预后相关，CD68是预测PNETs预后的独立危险因素。

Objective To investigate the assessed value of tumor-associated macrophages （ TAMs ） and KIT expression for liver metastasis in pancreatic neuroendocrine tumors （PNETs） and patients′outcome. Methods A total of 79 patients who underwent surgical resection and pathologically diagnosed as PNETs in the Department of Hepatopancreatobiliary Surgery in Sun Yat-sen Memorial Hospital from January 1995 to May 2015 were enrolled.The immunohistochemical staining of CD68 and KIT were detected and the correlations with clinicopathological factors were analyzed.Results Of 79 PNETs cases, CD68 and KIT in tumor tissue were overexpressed in 30（38%） and 35（44.3%） cases, respectively.CD68 overexpression was associated with tumor infiltration （ P〈0.001 ）, AJCC stage 7 （ P〈0.001 ）, liver metastasis （ P〈0.001 ） and early recurrence （P=0.019）.Patients with low CD68 level had significantly better survival than those with high CD68 expression （ P=0.0002 ）.KIT overexpression was correlated with WHO 2010 and AJCC stage 7 （P〈0.001;P=0.002）, nonfunctional status of the tumor （P=0.002） and liver metastasis （P=0.026）. The survival period of patients with low KIT expression was greatly longer than those with high KIT level （P=0.0013）.CD68 and KIT co-overexpression was observed in patients with tumor invasion （P〈0.001）,advanced WHO and AJCC stage （both P〈0.001） and better prognostic survival （P=0.0057）.Multivariate analysis showed that CD68 overexpression （HR：2.9;95%CI：1.16-7.23;P=0.033） was an independent prognostic factor for PNETs.Conclusions CD68 and KIT overexpression is correlated with advanced disease stage, higher risk for liver metastasis and worse survival.CD68 is an independent prognostic factor for PNETs.