Flt-4在不同级别脑星形细胞瘤中的表达意义

目的：探讨不同组织病理分级的脑星形细胞瘤中血管内皮生长因子受体3（Flt-4又称VEGFR-3）的表达意义。 方法： 采用免疫组织化学方法，检测50例不同级别脑星形细胞瘤患者手术切除标本中Flt-4、血管内皮生长因子（VEGF）的表达，并用抗FⅧ因子抗体标记瘤组织血管内皮细胞，计算肿瘤内微血管密度（IMVD）。 结果： Flt-4、VEGF总阳性表达率分别为52%（26/50）、60%（30/50）。Flt-4、VEGF均与脑星形细胞瘤病理分级呈显著正相关（等级相关系数分别为0.359、0.360,P＜0.05）。 结论： 脑星形细胞瘤中有Flt-4表达，主要表达于血管内皮细胞和部分肿瘤细胞，Flt-4既可是内皮细胞自分泌产生，部分还可来自瘤细胞的旁分泌；脑星形细胞瘤中Flt-4阳性表达的脉管是血管；Flt-4的表达与星形细胞瘤的病理分级相关     

星形细胞肿瘤的病理诊断和鉴别诊断

星形细胞肿瘤是具有星形胶质细胞分化特点的肿瘤 ,是最为多见的颅内胶质瘤 ,占神经上皮组织肿瘤的 6 0 %。星形细胞肿瘤见于各个年龄期 ,总的来说成人的星形细胞肿瘤多出现在大脑半球内 ,儿童的星形细胞肿瘤多出现在小脑、丘脑下部以及脑干部位。星形细胞肿瘤依据肿瘤细胞分化不良的程度和肿瘤组织的特点可以分为分化好的 ,即所谓低度恶性的星形细胞瘤和分化差的 ,即所谓高度恶性的胶质母细胞瘤 ;星形细胞瘤又因其生长方式的不同呈现不同的临床生物学特点 ,一类是大脑内弥漫浸润生长的星形细胞瘤 ,有别于脑内局限生长的星形细胞瘤 ,前者大多…     

Survivin在脑星形细胞瘤中的表达及其与COX-2相关性研究

目的：检测Survivin、COX-2在不同级别脑星形细胞瘤中的表达，探讨二者之间是否具有相关性，分析其参与肿瘤发生的机制。方法：采用免疫组化S-P法检测Survivin、COX-2在不同级别的星形细胞瘤中表达情况。结果：Survivin在星形细胞瘤Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级中的阳性表达率呈现增高趋势。在高分化组中呈散在的弱阳性表达，而在低分化组中表达明显增强，与高分化组有显著差异（χ^2=11.20，P〈0．01）；COX-2在星形细胞瘤Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级中的阳性表达率呈现增高趋势。在高分化组中呈散在的弱阳性表达，而在低分化组中表达明显增强，与高分化组有显著差异（χ^2=6．67，P〈0．01）；根据Spearman等级相关分析，Survivin与COX-2具有相关性（rs=0．481，P〈0．01）。结论：Survivin与COX-2的阳性表达率随星形细胞瘤恶性程度的增高呈明显增高的趋势，在脑星形细胞瘤中Survivin、COX-2的表达不是两个孤立的事件，二者可能在某个环节上有一定联系，在肿瘤的形成过程中可能具有协同作用，导致细胞无限增殖和失分化，从而使肿瘤呈现恶性生物学行为。     

疑似星形细胞瘤的脱髓鞘假瘤

目的 探讨脱髓鞘假瘤的临床病理特征，提高对该疾病的认识。方法 对2例脱髓鞘假瘤进行组织学观察、髓鞘染色和免疫组织化学染色。结果 病变区呈多灶性分布，可见大量成熟淋巴细胞在血管周围呈套袖状分布。其周围脑组织有大小不一的疏松的、重者呈空泡状的髓鞘脱失区，其间可见多少不等的巨噬细胞。大量增生的星形胶质细胞和脑组织疏松区相互交错，其胞质丰富、嗜酸性似肥胖型星性细胞，并见少量双核细胞及散在核分裂象。免疫表型：GFAP和vimentin在增生的星形细胞中弥漫阳性表达，CD68在巨噬细胞显示阳性表达，CD34在血管内皮细胞呈阳性表达，CD45在淋巴细胞呈阳性表达。结论 脱髓鞘所致的多灶性疏松改变、淋巴细胞的套袖状分布和巨噬细胞的弥漫分布是其基本特点。脱髓鞘假瘤在组织学形态上需与星性细胞瘤(尤其是肥胖型星型细胞瘤)、中枢神经系统淋巴瘤、神经节细胞瘤和少突胶质细胞瘤相鉴别。     

毛细胞黏液样型星形细胞瘤的临床病理学观察

目的探讨毛细胞黏液样型星形细胞瘤的临床病理学特点。方法观察3例毛细胞黏液样型星形细胞瘤的光镜形态,采用EnVision法免疫组织化学标记胶质纤维酸性蛋白（GFAP）、CD34、Ki-67,并结合文献复习分析其生物学行为。结果3例均为女性,年龄分别为9个月、10岁和19岁。1例发生于视交叉,2例发生于第三脑室（近鞍区部位）。镜下由双极性的梭形细胞组成,间质内含有大量的黏液。肿瘤内的血管明显增生,部分区域内瘤细胞显示以血管为中心性生长。3例切片内均未见到经典型毛细胞星形细胞瘤中的双相性形态,也未见Rosenthal纤维和嗜酸性颗粒小体。免疫标记显示,瘤细胞强阳性表达GFAP,瘤细胞增殖指数（Ki-67）〈1％。CD34标记显示清晰瘤内增生的血管。结论毛细胞黏液样型星形细胞瘤是毛细胞星形细胞瘤的一种独特亚型,在组织学上与毛细胞星形细胞瘤有不同之处,临床上较毛细胞星形细胞瘤更具有侵袭性。部分病例也可发生于儿童和青少年。GFAP标记有助于该瘤的诊断和鉴别诊断。     

星形胶质细胞瘤干细胞的体外分离、培养与鉴定

背景：肿瘤干细胞理论认为肿瘤中存在一小部分具有无限增殖潜能和自我更新能力,能够分化为成熟细胞表型的干细胞样细胞,对肿瘤发生、增殖、侵袭起关键作用。 目的：建立体外分离、培养与鉴定星形胶质细胞瘤干细胞的方法。 方法：采用直接培养法分离培养星形胶质细胞瘤干细胞。参照神经干细胞培养条件,进行体外培养。观察其增殖、分化并进行巢蛋白、CD133免疫细胞化学鉴定和诱导分化后神经元特异性烯醇化酶、胶质纤维酸性蛋白及O4免疫细胞化学鉴定。 结果与结论：培养7-10 d,可形成大量悬浮生长巢蛋白及CD133免疫阳性的神经球,经诱导分化后细胞呈神经元特异性烯醇化酶、胶质纤维酸性蛋白或O4免疫阳性。提示星形胶质细胞瘤中存在具有神经干细胞特性的肿瘤干细胞。CD133和巢蛋白是星形胶质细胞瘤干细胞重要的表面标记,可以用于星形胶质细胞瘤干细胞的分离。     

星形细胞肿瘤磁敏感成像与动态对比剂MR灌注加权成像的相关性研究

目的：探讨星形细胞肿瘤磁敏感加权成像（ SWI)半量化与动态对比剂增强MR灌注加权成像（ PI)的相关性。方法回顾性分析98例经手术病理证实星形细胞肿瘤患者的术前SWI及PI检查资料。测量SWI中肿瘤内磁敏感低信号区（ ITSHIA)半量化数据,以及PI中肿瘤内实性部分最大相对脑血流量值（ rrCBV瘤内max )和瘤周区最大相对CBV值（ rrCBV瘤周max )。应用Kruskal-Wallis H检验比较不同病理分级星形细胞肿瘤间rrCBV瘤内max与rrCBV瘤周max的差异,比较不同级别肿瘤间灌注热点区与ITSHIA形态的对应情况;应用Spearman相关性检验比较不同级别肿瘤间SWI中各半量化指标与PI中rrCBV瘤内max与rrCBV瘤周max的相关性。结果星形细胞肿瘤rrCBV瘤内max值（ rs =0．662,P<0．01)及rrCBV瘤周max值（rs =0．794,P<0．01)与其分级显著相关。毛细胞型星形细胞瘤rrCBV瘤内max高于Ⅱ级星形细胞瘤,与Ⅲ级肿瘤类似;而 rrCBV瘤周max与Ⅱ级星形细胞瘤差异无统计学意义（ P >0．05),却低于高级别肿瘤。星形细胞肿瘤的ITSHIA半量化指标与rrCBV瘤内max与rrCBV瘤周max值呈显著线性正相关。星形细胞肿瘤内灌注热点区与ITSHIA不完全对应。结论星形细胞肿瘤SWI指标与PI指标密切相关,二者对于术前评估星形细胞肿瘤的病理分级同样具有较高价值。灌注热点区与ITSHIA并不完全相同,可能与二者显示肿瘤内血管生成的机制不同有关。     

本刊2006年第8期重点内容预告

2006年第8期重点号为神经系统疾病，主要栏目和文章如下。专家论坛：脑肿瘤：从形态分类到分子分类。论著：脑多形性黄色瘤型星形细胞瘤的临床病理观察；中枢神经系统非典型畸胎样／横纹肌样瘤临床病理及免疫表型特征；阿尔茨海默病发病机制中β淀粉样蛋白对星形胶质细胞和神经细胞α7尼古丁受体的影响；整合素β1及纤连蛋白、层粘连蛋白对胶质瘤细胞浸润性的影响。     

脑星形细胞源性肿瘤免疫组化染色形态定量及其临床意义

用抗胶质纤维酸性蛋白(GFAP)抗体对呈形细胞源性肿瘤进行免疫组化染色,测定75例肿瘤的GFAP阳性程度和43例肿瘤的GFAP细胞灰度,分析肿瘤GFAP含量和肿瘤分化的关系。结果高分化的星形细胞瘤90%病例的阳性程度为强阳性.平均细胞灰度为25.17级,中度分化的间变型星形细胞瘤88%病例为中度阳性或强阳性,平均细胞灰度为30.55级,但其中2例分别为25级和38.4级。低分化的胶质母细胞瘤75%病例呈弱阳性,平均细胞灰度为34.1级,结果表明:除少数例外.肿瘤的GFAP含量与肿瘤的分化程度及预后密切相美。     

人脑星形细胞瘤纤溶酶原激活抑制因子1基因表达研究

目的研究人脑星形细胞瘤纤溶酶原激活抑制因子１（ＰＡＩ１）基因表达及其临床意义。方法采用Ｎｏｒｔｈｅｒｎ杂交和免疫组化ＡＢＣ方法检测３６例人脑星形细胞瘤ＰＡＩ１ｍＲＮＡ和蛋白表达，分析其与临床病理因素之间的关系。结果所有星形细胞瘤组织均可表达３．０ｋｂ和２．２ｋｂ的ＰＡＩ１ｍＲＮＡ转录物；高分级星形细胞瘤ＰＡＩ１ｍＲＮＡ表达水平显著高于低分级星形细胞瘤（Ｐ＜００１）；正常脑组织未检测出ＰＡＩ１ｍＲＮＡ表达。ＰＡＩ１ｍＲＮＡ表达水平与星形细胞瘤的坏死（ｒ＝０．５１，Ｐ＜０．０１）、微血管数（ｒ＝０．３３，Ｐ＜０．０１）及脑水肿（ｒ＝０．２７，Ｐ＜０．０１）呈显著正相关，与患者性别、年龄及瘤体大小无显著相关性。免疫组化染色显示，ＰＡＩ１蛋白主要分布在高分级星形细胞瘤的瘤细胞和内皮细胞，尤以血管增殖部位和坏死灶周围较为显著，低分级星形细胞瘤呈低水平表达。结论ＰＡＩ１基因表达与人脑星形细胞瘤的分级、坏死、血管生成及脑水肿密切相关，可作为星形细胞瘤恶性程度的分子标记。     

Clinicopathological and immunohistochemical features of three pilomyxoid astrocytomas: Comparative study with 11 pilocytic astrocytomas

Pilomyxoid astrocytoma, first described by Tihan et al ., was recently included as an established variant of pilocytic astrocytoma in the World Health Organization classification of CNS tumors. Histologically, it much resembles pilocytic astrocytoma, but monomorphic myxoid tumor of pilocytic cells with prominent angiocentric growth pattern without Rosenthal fibers or eosinophilic granular bodies is characteristic of pilomyxoid astrocytoma. Pilomyxoid astrocytoma is thought to be more aggressive with more frequent local recurrence as well as cerebrospinal spread. The authors recently encountered a case of pilomyxoid astrocytoma, therefore the purpose of the present study was undertake a retrospective review of pilocytic astrocytomas previously diagnosed during the past 10 years. Consequently, two of them were found to have histological features suggestive of pilomyxoid astrocytoma and both involved multiple recurrence, suggesting aggressive behavior in comparison to pilocytic astrocytoma. Therefore, knowledge of this entity is essential to surgical pathologists and clinicians for patient management.     

Secondary glioblastoma with advanced neuronal immunophenotype

We describe an unusual progression of astrocytoma into secondary glioblastoma exhibiting advanced neuronal immunophenotype. A tumor of the left frontal lobe of a 35-year-old man was diagnosed as astrocytoma. The tumor was treated by partial removal with postoperative chemoradiotherapy, followed by extensive removal of the residual regrowing tumor 5 month later. A secondary tumor was discovered and partially resected 8 years later, but the patient died 11 months following the operation due to extensive tumor progression showing subarachnoidal and intraventricular dissemination. The secondary tumor was small cell-predominant, highly proliferative tumor with an extremely high MIB-1 labeling index (80%). Unexpectedly, most of the tumor cells were positive for neuronal markers (synaptophysin and NeuN), but not for glial fibrillary acidic protein (GFAP). Retrospective examination of the original tumor revealed not only diffuse GFAP expression, but also neuronal marker expressions in small numbers of tumor cells that were hard to discriminate from the other cells on hematoxylin-eosin (HE) stain. This way of malignant progression of astrocytoma was quite unusual. Although the secondary tumor was classified as glioblastoma according to World Health Organization (WHO) classification (2000), it might be categorized into new variants of malignant glioneuronal tumors proposed recently.     

水通道蛋白4和人星形胶质细胞瘤在体内增殖和瘤周水肿的相关性研究

目的：研究水通道蛋白4（aquaporin-4, AQP4）和人星形胶质细胞瘤在体内增殖和瘤周水肿的相关性。方法建立人星形胶质细胞瘤裸鼠模型; EdU法检测细胞增殖;免疫组织化学法检测肿瘤组织内CD34阳性细胞表达,检测肿瘤组织微血管密度;免疫印迹法测AQP4蛋白表达;以人脑正常星形胶质细胞为阴性对照。结果细胞皮下注射一周后可见肿瘤长出, EdU法检测肿瘤增殖能力随肿瘤恶性程度增加而增大,免疫组织化学检测提示高度恶性组较低度恶性组具备更高的微血管密度, AQP4蛋白表达随恶性程度增加而增加。结论水通道蛋白4的表达水平和人星形细胞瘤增殖和瘤周水肿程度密切相关。     

Minigemistocytic astrocytoma with frequent apoptoses: Analysis of tumor growth

A rare glial tumor known as 'minigemistocytic astrocytoma (gliofibrillaty oligodendroglioma)' is reported in a 73 year old Japanese male. A low-density area found by computed tomography and thought to be an operative scar remaining after hematoma in the right frontal lobe of the cerebrum had been followed for 10 years. This area, however, had been accompanied by a cyst for 2 years and had developed gradually for 1 year prior to dissection. The tumor was poorly demarcated from the surrounding normal tissue macroscopically at operation. Microscopically, the tumor consisted of small gemistocytic cells in uniform sheets intersected by a small vascular stroma with frequent eosinophilic granular bodies, mitoses and apoptotic bodies. lmmunohistochemical examination for glial fibrilliary acidic protein (GFAP) revealed remarkable positive reactivity in the perinuclear cytoplasm, but no immunoreactivity for vimentin or Leu 7 was found. Electron microscopically, rich filaments amngfd in parallel bundles were found in the neoplastic cells. These histological findings are closely consistent with those of previously reported minigemistocytic astrocytoma cases. The GFAP-rich minigemistocytic astrocytoma with granular bodies and frequent mitoses in the present case is considered to indicate a higher degree of astrocytic differentiation and malignant potential than previous cases. The frequent apoptoses, however, might inhibit tumor growth in this case.     

毛细胞黏液样星形细胞瘤的研究进展

毛细胞黏液样星形细胞瘤（pilomyxoid astrocytoma,PMA）是2007年WHO中枢神经系统肿瘤病理学中新提出的一个分类。它是毛细胞星形细胞瘤（pilocytic astrocytoma,PA）的特殊亚型,患者发病年龄更早,视交叉/下丘脑是病变的常见部位。近些年也有成人PMA及特殊部位PMA的报道。组织学见双极梭形细胞围绕血管生长,有黏液样背景,无PA常见的Rosenthal纤维和嗜酸性颗粒小体。与PA相比,患者预后较差,易局部多次复发或经脑脊液转移甚至死亡。PMA复发后可演变呈典型的PA。     

人星形细胞瘤中单核细胞在血管生成过程中的作用

目的探讨单核细胞在人星形细胞瘤血管生成(Angiogenesis)过程中的作用.方法应用硷性纤维母细胞生长因于(bFGF)的抗体,通过免疫组织化学手段,在组织学切片上探讨单核细胞和bFGF在人星形细胞瘤血管生成过程中的作用.结果1.bFGF在血管内皮细胞中的表达强度随血管密度增加而增加,并与血管密度之间存在回归直线,P＜0.01.2.28.3%的切片中单核细胞表达bFGF,表达bFGF的单核细胞可见于血管内,或沿血管壁呈规则排列,也可成堆靠近血管壁,并使血管呈出芽生长.结论肿瘤内新生的血管内皮细胞可产生bFGF;单核细胞不但产生bFGF,而且参与肿瘤内的血管生成,它可能是血管内皮细胞的前期细胞.     

Intratumoral Heterogeneity of Genomic Imbalance in a Case of Epithelioid Glioblastoma with BRAF V600E Mutation

Epithelioid glioblastoma is among the rarest variants of glioblastoma and is not formally recognized in the World Health Organization classification; it is composed of monotonous, discohesive sheets of small, round cells with eccentric nuclei and eosinophilic cytoplasm devoid of cytoplasmic stellate processes, showing the retention of nuclear staining of INI‐1 protein. Here, we report a case involving a 22‐year‐old man with a right occipital lobe tumor, which comprised mainly epithelioid tumor cells with a small area of diffusely infiltrating less atypical astrocytoma cells showing a lower cell density. Array comparative genomic hybridization separately performed for each histologically distinct component demonstrated eight shared copy number alterations (CNAs) and three CNAs observed only in epithelioid cells; one of the latter was a homozygous deletion of a tumor suppressor gene, LSAMP, at 3q13.31. BRAF V600E mutation was observed both in epithelioid tumor cells and in diffusely infiltrating less atypical astrocytoma cells. Our findings suggest that the regional loss of LSAMP led to the aggressive nature of epithelioid cells in the present case of epithelioid glioblastoma.     

Follow-up evaluation of radiation-induced DNA damage in CSF disseminated high-grade glioma using phospho-histone H2AX antibody

Cytological examination of cerebrospinal fluid (CSF) is used not only for the diagnosis of spinal disease, but also to assess the postoperative effect of treatment. We experienced a case of high-grade glioma in disseminated CSF, and retrospectively examined the clinical, pathological and cytological features. We further investigated radiation-induced DNA damage in glioma cells using phospho-Histone H2AX antibody. A five-year-old boy received a clinical diagnosis of optic nerve glioma, and was followed-up for three months after chemotherapy. Magnetic resonance imaging was repeated, revealing abnormalities in other brain areas. The pathological diagnosis was anaplastic astrocytoma. CSF dissemination was detected, and increases in the number and mitosis of tumor cells were observed in CSF cytology. After radiotherapy the tumor cells in CSF decreased markedly. On cytomorphologic and immunocytochemical evaluation post-irradiation, tumor cells showed vacuolation of both the nucleus and cytoplasm, degeneration of nuclear chromatin, and alteration of the phospho-Histone H2AX expression, compared with tumor cells before the irradiation. CSF cytology is an effective means of evaluating DNA damage in tumor cells after irradiation, and may be useful in assessing the therapeutic response.