实时荧光定量PCR微卫星分析技术检测少突胶质细胞肿瘤染色体1p、19q和10q杂合性缺失

目的建立检测脑胶质瘤染色体1p、19q和10q杂合性缺失(LOH)的实验室新方法。方法采用Taqman探针法对38例少突胶质细胞肿瘤标本进行染色体1p、19q和10q LOH检测。结果 38例少突胶质细胞肿瘤染色体中有25例(65.7%)发生1p LOH,26例(68.4%)发生19q LOH,5例(13.2%)发生10q LOH。结论实时荧光定量PCR微卫星分析技术快速、准确性高,可以用于脑胶质瘤标本染色体LOH的检测。     

室间孔囊性少突胶质细胞瘤1例

病例女,14岁。头痛、头晕伴视物模糊10余天,进行性加重伴呕吐4天。专科检查无特殊。MRI检查:左侧室间孔区见类圆形长T1、长T2信号,大小2.2 cm×2.0 cm,FLAIR囊腔呈稍高信号,囊壁右后份见条状短T1、短T2信号,DWI囊腔呈低信号、右后份病变呈稍高信号,增强扫描囊壁右后份轻度强化(图1~6),透明隔稍向右移位。     

少突胶质细胞瘤1p/19q检测临床意义研究

目的研究少突胶质细胞瘤样本1p/19q染色体缺失与患者预后的关系。方法用荧光原位杂交方法检测37例少突胶质细胞瘤样本,分析样本中1p/19q缺失情况。结果在对37例样本的检测中,1p缺失25例（67.5%）、19q缺失23例（62.2%）、1p/19q共缺失20例（54.1%）。其中少突胶质细胞瘤正常组、1p/19q共缺失、仅1p缺失和仅19q缺失平均生存时间分别为41、85、67和45个月,中位生存时间分别为41、85、78和64个月。1p/19q共缺失和1p缺失患者的预后较正常组和19q缺失组更好。结论 1p/19q染色体缺失是少突胶质细胞瘤的重要分子生物学标志物,在预后判断,肿瘤分层上有重要意义。     

囊性少突胶质细胞瘤MRI表现

目的 探讨囊性少突胶质细胞瘤的MRI表现。方法 回顾性分析经手术病理证实的10例囊性少突胶质细胞瘤的MRI表现。结果 10例中,8例病灶位于幕上,2例病灶位于幕下小脑蚓部;9例为单发病灶,仅1例为多发病灶;完全囊性病变4例,大囊伴类结节病变3例,多房囊性病变3例;7例病灶囊壁光滑、规则,3例囊壁局部凹陷、毛糙。3例病灶可见钙化。9例轻度瘤周水肿,1例中、重度水肿。增强后3例病灶实性成分明显强化,3例病灶囊壁呈明显环形强化,1例囊壁呈局灶性强化。结论 COD术前准确诊断较难,其MRI表现具有一定特点。对发生于幕上表浅部位、完全囊性或伴有结节和/或分隔的大囊性病变,应考虑到本病可能。     

变性高效液相色谱检测少突胶质细胞瘤1p杂合性缺失

目的 建立临床检测少突胶质细胞瘤1p杂合性缺失的手段.方法 提取肿瘤组织及患者外周血DNA,利用聚合酶链式反应扩增微卫星位点后行变性高效液相色谱检测.结果 以患者外周血作对照,可明确显示肿瘤标本微卫星位点杂合性缺失情况,从而判断患者1p杂合性缺失情况.结论 该方法能直观便捷分析出患者1p杂合性缺失情况.     

发生于少突胶质细胞肿瘤的胶质肉瘤（少突胶质肉瘤）临床病理学研究（英）

神经胶质肉瘤是形态学上由神经胶质和肉瘤成分组成的双向性肿瘤。伴有少突神经胶质成分的胶质肉瘤仅有罕见病例报道。作者对7例同时伴有少突胶质细胞瘤和肉瘤成分的患者进行了研究。在所有病例中，胶质瘤和肉瘤区域免疫荧光原位杂交均发现1p／19q的缺失。患者被诊断神经胶质肉瘤的平均年龄为48岁（36-68岁）女男之比为5：2。     

少突胶质细胞对中枢神经系统再生抑制作用的研究进展

胶质细胞在中枢神经损伤与修复中如同一把双刃剑：一方面促进轴突再生,产生一些神经营养因子支持轴突生长;另一方面又抑制轴突生长,局部胶质细胞形成坚硬的胶质瘢痕并分泌一些抑制性因子,阻碍轴突的生长、穿过等;然而少突胶质细胞的细胞膜及成熟中枢神经系统中广泛存在的髓鞘又是影响中枢神经系统再生的最重要因素之一。了解少突胶质细胞表达的抑制性蛋白抑制作用的机制对神经再生新途径的开辟具有重要意义。     

不同级别少突胶质细胞瘤影像病理对照

目的：通过探讨不同级别少突胶质细胞瘤的影像学特点并与病理表现对照,为少突胶质细胞瘤的临床治疗提供帮助。方法：回顾性分析57例经病理证实的不同级别少突胶质细胞瘤的影像表现,并和病理作对照。结果：少突胶质细胞瘤（WHO Ⅱ级）35例,中位年龄34岁,好发于额、顶叶皮髓质交界区,边界模糊,29例CT呈稍低密度,6例CT呈混杂密度,31例T1WI呈低信号,4例呈等信号,35例T2WI呈高信号,增强扫描32例呈轻度强化,3例呈不均匀强化,32例伴钙化,7例囊变,8例出血,5例伴瘤周水肿;间变少突胶质细胞瘤（WHO Ⅲ级）22例,中位年龄32岁,好发于额、顶、颞皮髓质交界区,边界较清,10例CT呈稍低密度,12例CT呈混杂密度,19例T1WI例呈低信号,3例呈等信号,19例T2WI呈高信号,增强扫描2例轻度强化,20例呈明显强化,3例伴钙化,12例囊变坏死,9例出血,22例伴瘤周水肿。结论：间变型少突胶质细胞瘤（WHO Ⅲ级）在囊变坏死、出血、瘤周水肿及强化形式方面较少突胶质细胞瘤更加明显,这些影像学特征有助于对该类肿瘤术前分级的诊断,为肿瘤的临床治疗提供帮助。     

不同分级少突胶质细胞肿瘤的MRI诊断

目的探讨不同分级少突胶质细胞肿瘤的MRI表现特点,为临床治疗方法的选择提供参考。方法回顾性分析59例不同分级少突胶质细胞肿瘤的MRI表现,并和病理结果对照分析。结果本组不同分级少突胶质细胞肿瘤共59例,其中少突胶质细胞瘤(WHOⅡ级)37例,好发于额、顶叶交界区,34例边界模糊,33例T1WI呈低信号,37例T2WI呈高信号,增强扫描30例呈轻度强化,7例囊变,8例出血,5例伴瘤周水肿;间变少突胶质细胞瘤22例,好发于额、顶、颞叶交界区,21例边界较清,19例T1WI例呈低信号,T2WI呈高信号,增强扫描17例明显强化,12例囊变坏死,9例出血,22例伴瘤周水肿。结论不同分级少突胶质细胞肿瘤MRI表现有一定差异。     

基于T2WI影像组学模型可预测低级别胶质瘤1p/19q的缺失状态

目的  基于磁共振T2WI构建影像组学模型,预测低级别胶质瘤1p/19q缺失状态的价值。 方法  回顾性分析本院经病理证实的154例低级别胶质瘤患者（1p/19q共缺失100例,1p/19q非共缺失54例）,按照分层抽样7∶3分成训练集和验证集。使用3D-Slicer软件对肿瘤区域进行手动分割,用pyradiomics进行特征提取。临床资料的分析采用t检验/χ²检验;影像组学特征采用方差法和10折交叉验证的LASSO算法进行筛选,最后建立支持向量机、高斯朴素贝叶斯、K-近邻、逻辑回归模型,采用ROC曲线的曲线下面积值和sklearn分类报告中的参考指标（准确度、敏感度、特异性、F1分数）进行效能评价。 结果  4种模型中,支持向量机的曲线下面积值最高,训练集和验证集分别为0.95、0.91;参考指标中表现最佳为K-近邻,其准确度、敏感度、特异性及F1分数分别为0.87、0.97、0.70、0.91;其次为支持向量机,各项指标与模型平均值相当。 结论  基于T2WI影像组学模型可以有效地预测低级别胶质瘤1p/19q的缺失状态。     

Dural metastasis of atypical extraventricular neurocytoma with the codeletion of chromosomes 1p/19q

Extraventricular neurocytoma (EVN) is a rare neoplasm described in the 2007 World Health Organization classification of tumours of the nervous system. Due to the rarity of the tumour, there is limited literature available. The clinical characteristics, pathological features, biological behaviour and outcome of EVN remain unclear, and there are challenges regarding its diagnosis and management. The present case was a 75-year-old man who had been experiencing slow responses to stimuli for 1 month prior to hospital admission. A diagnosis of atypical EVN was made on the basis of pathology and immunohistochemistry results. Atypical pathological features included vascular proliferation, the presence of mitosis and a high MIB-1 (an antibody against Ki-67) labelling index. The disease recurred 7 months after the initial complete resection and radiation treatment, presenting with dural metastasis and codeletion of chromosomes 1p/19q. The present case history and treatment course are discussed with respect to the literature.     

1p/19q分子遗传学改变在少突胶质细胞瘤和星形细胞瘤鉴别诊断中意义

目的：探讨1p/19q分子遗传学改变在少突胶质细胞瘤和星形细胞瘤鉴别诊断中的意义。方法：少突胶质细胞瘤和星形细胞瘤共63例,采用荧光原位杂交技术检测染色体1p/19q分子遗传学改变。结果：1p/19q呈多倍体改变5例,其中星形细胞瘤3例,少突胶质细胞瘤2例;1p和19q杂合性缺失58例,其中少突胶质细胞肿瘤41例,星形细胞肿瘤17例。少突胶质细胞瘤染色体1p,19q及1p/19q缺失率分别为65.9％,68.3％和58.5％,星形细胞瘤分别为17.6％,29.4％和1 7.6％,差异均有统计学意义(P=0.001,P=0.006,P=0.004)。少突胶质细胞瘤中1p/19q杂合性缺失24例,21例(87.5％)有典型少突胶质细胞瘤形态学特征,1p/19q未发生缺失17例,9例(52.9％)有典型组织学特征,差异有统计学意义(P=0.014)。结论：少突胶质细胞瘤1p/19q杂合性缺失率高于星形细胞瘤。组织学特点较典型的少突胶质细胞肿瘤更倾向于合并1p/19q杂合性缺失。1p/19q多倍体多见于星形细胞亚型肿瘤。     

体素内不相干运动MRI预测脑胶质瘤异柠檬酸脱氢酶及1p/19q分子分型

目的 观察体素内不相干运动(IVIM)MRI预测脑胶质瘤异柠檬酸脱氢酶(IDH)及其1p/19q分子分型的价值。方法 回顾性纳入32例脑胶质瘤患者,根据IDH检测结果分为IDH突变组(n=18)及野生组(n=14),并根据染色体1p/19q检测结果将突变组分为1p/19q共缺失亚组(n=5)与非共缺失亚组(n=13)。比较组间、亚组间一般资料和IVIM参数,包括表观弥散系数(ADC)、慢弥散系数(D)、快弥散系数(D^*)、灌注分数(f)、相对ADC(rADC)、相对D(rD)、相对D^*(rD^*)及相对f(rf)值,分析其预测脑胶质瘤分子分型的效能。结果 突变组患者年龄小于野生组(t=－4.274,P=0.001)。突变组ADC、rADC及D值高于野生组,D^*及rf值低于野生组(P均＜0.05)。以ADC、rADC、D、D^*及rf值预测脑胶质瘤IDH分型的曲线下面积(AUC)分别为0.80、0.76、0.74、0.78及0.72。共缺失亚组D^*值大于非共缺失亚组(P＜0.05);以D^*值预测IDH突变型脑胶质瘤1p/19q分型的AUC为0.88。结论 脑胶质瘤ADC、rADC、D、D^*及rf值均有助于预测IDH突变,D^*值还有助于预测染色体1p/19q共缺失。     

α-地中海贫血/精神发育迟滞综合征X染色体相关基因的表达及1p/19q遗传学改变在星形细胞瘤、少突胶质细胞瘤及少突星形细胞瘤诊断中的意义

目的探讨a-地中海贫血/精神发育迟滞综合征X染色体相关基因（ATRX）的表达及1p/19q遗传学改变在星形细胞瘤、少突胶质细胞瘤及少突星形细胞瘤诊断中的意义。方法星形细胞瘤、少突胶质细胞瘤及少突星形细胞瘤共53例,采用免疫组化及荧光原位杂交技术检测ATRX的表达及染色体1p/19q分子遗传学改变。结果星形细胞瘤、少突胶质细胞瘤及少突星形细胞瘤中ATRX突变率（ATRX表达为阴性）分别为60.0%、44.4%及50.0%;星形细胞瘤染色体1p及19q单缺失和1p/19q共缺失率均为0%,少突胶质细胞瘤缺失率分别为54.5%、0%和45.5%,少突星形细胞瘤缺失率分别为12.5%、0%和0%,少突胶质细胞瘤染色体1p/19缺失率（包括共缺失及单缺失）与非少突胶质细胞肿瘤（包括星形细胞瘤及少突星形细胞瘤）比较差异有统计学意义（P=0.032）。联合检测ATRX表达及1p/19q缺失情况,少突星形细胞瘤与星形细胞瘤及少突胶质细胞瘤比较差异有统计学意义（P=0.046,P=0.003）。结论染色体1p/19q缺失主要发生在少突胶质细胞瘤中,对少突胶质细胞瘤的诊断具有重要价值;少突星形细胞瘤与星形细胞瘤的遗传学分子改变具有一定的差异性。     

NOTCH2 Is Neither Rearranged nor Mutated in t(1;19) Positive Oligodendrogliomas

The combined deletion of 1p and 19q chromosomal arms is frequent in oligodendrogliomas (OD) and has recently been shown to be mediated by an unbalanced t(1;19) translocation. Recent studies of 1p/19q co-deleted OD suggest that the NOTCH2 gene is implicated in oligodendrocyte differentiation and may be involved in this rearrangement. The objective of the present study was to analyze the NOTCH2 locus either as a chromosomal translocation locus that may be altered by the 1p/19q recurrent rearrangement or as a gene that may be inactivated by a two hit process. We performed an array-CGH analysis of 15 ODs presenting 1p/19q co-deletion using a high-density oligonucleotide microarray spanning 1p and 19q pericentromeric regions with 377 bp average probe spacing. We showed that the 1p deletion extends to the centromere of chromosome 1 and includes the entire NOTCH2 gene. No internal rearrangement of this gene was observed. This strongly suggests that the t(1;19) translocation does not lead to an abnormal NOTCH2 structure. The analysis of the entire NOTCH2 coding sequence was performed in four cases and did not reveal any mutation therefore indicating that NOTCH2 does not harbor genetic characteristics of a tumor suppressor gene. Finally, the detailed analysis of chromosome 19 pericentromeric region led to the identification of two breakpoint clusters at 19p12 and 19q11–12. Interestingly, these two regions share a large stretch of homology. Together with previous observations of similarities between chromosome 1 and 19 alphoid sequences, this suggests that the t(1;19) translocation arises from complex intra and interchromosomal rearrangements.     

抗梅毒治疗对妊娠结局及新生儿预后的影响

目的探讨抗梅毒治疗对妊娠梅毒患者的妊娠结局及新生儿预后的影响。方法对2013年1月-12月分娩的5 224例孕妇资料进行分析。所有孕妇均经过甲苯胺红不加热血清试验（TRUST）进行筛查,筛查阳性者再进行滴度检测和梅毒螺旋体被动颗粒凝集试验（TPPA）确诊妊娠合并梅毒患者128例。根据其是否经产前检查并治疗分为治疗组（79例）和未治疗组（49例）,观察并比较两组孕妇的结局及新生儿情况。结果两组孕妇妊娠结局差异较大,但差异无统计学意义（χ2=3.34,P〉0.05）;而两组新生儿预后情况比较则差异有统计学意义（χ2=9.14,P〈0.05）;且两组新生儿出生后立即取静脉血做血清学检测（TPPA和TRUST）,其TPPA均为阳性,TRUST阳性85例。结论孕前、孕早期进行梅毒筛查,早期发现妊娠梅毒者进行规范的抗梅毒治疗,对降低流产、死产、胎儿畸形和新生儿先天梅毒发生率具有重要意义。     

Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf/p53 pathway lesions but not p16 Ink4a loss

Breast cancers frequently progress or relapse during targeted therapy, but the molecular mechanisms that enable escape remain poorly understood. We elucidated genetic determinants underlying tumor escape in a transgenic mouse model of Wnt pathway-driven breast cancer, wherein targeted therapy is simulated by abrogating doxycycline-dependent Wnt1 transgene expression within established tumors. In mice with intact tumor suppressor pathways, tumors typically circumvented doxycycline withdrawal by reactivating Wnt signaling, either via aberrant (doxycycline-independent) Wnt1 transgene expression or via acquired somatic mutations in the gene encoding beta-catenin. Germline introduction of mutant tumor suppressor alleles into the model altered the timing and mode of tumor escape. Relapses occurring in the context of null Ink4a/Arf alleles (disrupting both the p16 Ink4a and p19 Arf tumor suppressors) arose quickly and rarely reactivated the Wnt pathway. In addition, Ink4a/Arf-deficient relapses resembled p53-deficient relapses in that both displayed morphologic and molecular hallmarks of an epithelial-to-mesenchymal transition (EMT). Notably, Ink4a/Arf deficiency promoted relapse in the absence of gross genomic instability. Moreover, Ink4a/Arf-encoded proteins differed in their capacity to suppress oncogene independence. Isolated p19 Arf deficiency mirrored p53 deficiency in that both promoted rapid, EMT-associated mammary tumor escape, whereas isolated p16 Ink4a deficiency failed to accelerate relapse. Thus, p19 Arf/p53 pathway lesions may promote mammary cancer relapse even when inhibition of a targeted oncogenic signaling pathway remains in force.