摘要目的 检测磷酸化组蛋白H3(PHH3)在胰腺神经内分泌肿瘤(PNENs)中的表达,探讨其对PNENs病理分级的意义.方法 回顾性分析2000年12月至2016年5月长海医院收治的283例PNENs患者的临床病理资料,将所有PNENs组织制成组织芯片,采用免疫组织化学方法检测PHH3、Ki67的表达.通过绘制PHH3的受试者工作特征曲线,计算曲线下面积,确定PHH3对PNENs分级的临界值.同时按国内外公认标准依据Ki67对PNENs进行分级.分析并比较PHH3、Ki67两种分级方法与PNENs临床病理特征、预后及两者之间的相关性.结果 本研究共纳入PNENs患者283例,其中男性132例,女性151例,年龄16 ～ 78岁,平均(50±1)岁;功能性PNENs 44例,无功能性PNENs 239例;肿瘤直径1.1 ～ 17 cm,平均(4.1±1.2) cm.PHH3法将283例患者分为G1级118例,G2级119例,胰腺神经内分泌瘤(PNET)G3级38例,胰腺神经内分泌癌(PNEC)G3级8例;Ki67法分为G1级127例,G2级116例,PNETG3级33例,PNECG3级7例.两种分级方法呈正相关关系(r=0.941,P＜0.001).PHH3表达及PNENs分级均与患者的年龄、性别及肿瘤有无功能、肿瘤部位无相关性(P值均＞0.05),而与肿瘤大小、组织学分级、淋巴结转移、TNM分期及患者预后呈正相关(P值均＜0.05).每例组织芯片免疫组织化学染色后观察PHH3的平均时间为9 min,观察Ki67的平均时间为45 min.结论 检测PNENs的PHH3表达可对PNENs进行病理诊断分级和预后评估,较Ki67分级法更准确和更便捷.

abstractsObjective To investigate the expression of phospho-histone H3 (PHH3) protein in pancreatic neuroendocrine neoplasms (PNENs) and explore its potential value for pathological grading of PNENs.Methods Clinical and pathological data of 283 patients with PNENs treated in Changhai Hospital from December 2000 to May 2016 were retrospectively analyzed.PNENs tissue chip was prepared,and immunohistochemistry was used to examine the expression of PHH3 and Ki67.The receiver operating characteristic curve for PHH3 was drawn and the area under the curve(AUC) was calculated to determine the cutoff value for PNENs grading.Ki67 was used for PNENs grading according to domestic and intemational criteria for PNENs classification.The relationship of PHH3 and Ki67 classification with clinical pathological features and prognosis of PNENs as well as the correlation between the two classification methods were analyzed.Results Of 283 patients,132 were male and 151 were female,aged from 16 to 78 years old.The average age was (50 ± 1) years old.There were 44 cases with functional PNENs and 239 with non-functional PNENs.The diameter of tumors ranged from 1.1 cm to 17 cm and the average diameter was (4.1 ± 1.2)cm.According to the Ki67 standard,there were 127,116,33 and 7 cases of Grade G1,G2,pancreatic neuroendocrine tumor(PNET) G3 and pancreatic neuroendocrine cancer(PNEC) G3.According to the PHH3 standard,there were 118,119,3 8 and 8 cases of Grade G1,G2,PNET G3 and PNEC G3.There was a positive correlation between the two grading criteria (r =0.941,P ＜0.001).PHH3 expression and PNENs grading were not correlated with age,gender,tumor functional or not and tumor locations (all P ＞ 0.05),but were both positively correlated with tumor size,histological grade,lymph node metastasis,TNM stage and prognosis (all P ＜0.05).The average time of observing PHH3 and Ki67 staining per case in the immunohistochemistry of tissue chip was 9 min and 45 min,respectively.Conclusions Detection of PHH3 expression in PNENs can be used for the pathological diagnosis,grading and prognostic evaluation,which was more accurate and convenient than Ki67 criteria.