HER2状态与脑膜瘤分级及复发的相关性

目的 探讨HER2、细胞增殖指标Ki-67、胸苷激酶1(TK1)与脑膜瘤分级和良性脑膜瘤复发的相关性.方法 按2007年WHO神经系统肿瘤分类分级标准选取良性未复发的脑膜瘤、不典型脑膜瘤及恶性脑膜瘤石蜡标本各20例,并选取间期良性复发的脑膜瘤石蜡标本20例,将实验对象分为4组:良性非复发组、良性复发组、不典型组及恶性组.采用免疫组织化学MaxVision法对4组石蜡切片进行HER2、Ki-67、TK1蛋白的检测;并运用双色荧光原位杂交(FISH)法检测HER2蛋白表达阳性样本的HER2基因扩增情况.结果 免疫组织化学:(1)良性非复发组、良性复发组、不典型组和恶性组脑膜瘤的HER2阳性的例数分别为3例(15%)、6例(30%)、7例(35%)和10例(50%),随恶性程度增加,HER2蛋白阳性率升高(P<0.05);良性复发组HER2阳性率高于良性非复发组(P<0.05);(2)良性非复发组Ki-67和TK1的标记指数(U)均分别低于不典型组和恶性组(P<0.05);不典型组低于恶性组(P<0.05),随着恶性程度增高,Ki-67、TK1 LI升高;且良性复发组高于良性非复发组(P<0.05);(3)HER2与Ki-67、TK1均呈正相关(均P<0.01),Ki-67与TK1呈正相关(P<0.05).FISH法:(1)在26例HER2蛋白阳性表达的脑膜瘤组织中HER2/neu基因的扩增率为26.9%(7/26);HER2蛋白表达3+、2+者HER2/neu基因扩增比例分别为3,/4和4/6,均多于1+者(均P<0.01),3+者与2+者比较差异无统计学意义(P>0.05).(2)26例HER2蛋白阳性表达的脑膜瘤组织中9例存在17号染色体的非整倍性(34.6%),但HER2蛋白表达1+、2+、3+者间17号染色体的非整倍性出现率差异均无统计学意义(均P>0.05).结论 HER2阳性且Ki-67或TK1 LI高提示脑膜瘤恶性程度较高或复发可能性较大.脑膜瘤组织中存在HER2/neu基因的扩增.HER2、Ki-67和TK1蛋白可能可以作为临床判断脑膜瘤生物学行为的参考指标.

Expression of HER2/neu in meningiomas: an immunohistochemistry and fluorescence in situ hybridization study

Objective To investigate the expression of HER2/neu, Ki-67 and TK1 protein in meningiomas in correlation with tumor grades and recurrence.Methods Twenty cases of each of the following types of meningiomas were selected for the study, namely: the benign non-recurrent, recurrent benign, atypical and malignant, according to the World Health Organization (WHO) histological classification of nervous system, 2007.Immunohistocbemistry study for HER2/neu, Ki-67 and TK1 protein was performed.HER2/neu gene amplification was detected using FISH.Cases with HER2 protein overexpression were studied by immunohistochemistry staining.The results of the biomarker assays were also used to study the correlationship with the tumor grades and tumor recurrency.Results Immunohistochemistry showed that the positive rates of HER2 expression in non-recurrence benign group, recurrence benign group,atypical group and malignant group were 3 cases( 15% ), 6 cases(30% ), 7 cases(35% ), and 10 cases(50%), respectively (P <0.05 ).A higher tumor grade was correlated with a higher rate of HER2/neu expression.The Ki-67 and TK1 labeling index (LI) in non-recurrence group were lower than those in the atypical or malignant group ( P < 0.05 ), whereas the atypical group had lower LI than that of the malignant group (P < 0.05 ).Higher levels of LI of Ki-67 and TK1 were correlated with higher tumor grades and recurrence of the benign meningiomas ( P <0.05 ).Expression of HEB2 was positively correlated with Ki-67 and TK1 (r = 0.445, P < 0.01 ;r = 0.501, P < 0.01, respectively), and there was a positive correlation between Ki-67 and TK1 ( r = 0.450, P < 0.01 ) as well.HER2/neu gene copy amplification in 7 of 26 cases(26.9% ) of HEB2 immunopositive meningiomas.The rates of HEB2/neu gene amplification were 0 in tumors with 1 + immunopositivity, 4/6 in tumor with 2 + immunopositivity and 3/4 in tumor with 3 +inununopositivity.HER2/neu gene amplification in 3 + and 2 + immunopositive cases had no statistical significance (P > 0.05 ).Aneuploidy of chromosome 17 existed in 9 of 26 of HER2 immunopositive meningiomas (34.6% ).However, the rates of chromosome 17 aneuploidy had no significant difference among tumors with variable HEB2/neu imumopositivity ( P > 0.05 ).Conclusions High levels of HER2 and Ki-67 or TK1 expression correlate with the increase of tumor grades and tumor recurrence.HEB2/neu gene amplification is seen in a subset of meningiomas with the protein expression (26.9% ).A combination of biomarker study including HER2/neu, Ki-67 and TK1 may be useful in predicting the biological behavior of meningiomas.