PTTG和VEGF在垂体腺瘤中的表达及其与微血管形成的关系

目的探讨垂体瘤转化基因（PTTG）和血管内皮生长因子（VEGF）在垂体瘤中的表达及其与肿瘤血管形成的关系，为进一步研究垂体瘤的抗血管治疗提供理论依据。方法利用免疫组化方法检测48例垂体瘤组织中PTTG、VEGF及微血管密度（MVD）的表达，并分析PTTG、VEGF的相关性以及与MVD和垂体腺瘤侵袭性的关系。结果PTTG和VEGF在垂体腺瘤中的阳性表达率分别为66．7％（32/48）和79．2％（38/48），PTTG和／或VEGF阳性表达的垂体腺瘤组织中的MVD值均显著高于PTTG和VEGF阴性者（P〈0．05），PTTG的表达与VEGF的表达呈明显正相关（P〈0．05）；PTTG、VEGF的表达与垂体腺瘤的侵袭性有关（P〈0．05）。结论PTTG、VEGF对肿瘤血管形成起重要作用，可能通过PTTG—VEGF调节旁路途径促进垂体腺瘤的肿瘤血管形成；PTTG、VEGF的表达可作为判断垂体腺瘤侵袭性的一项生物学指标，对判断预后也有一定的意义。     

MMP-9、VEGF和p16在垂体腺瘤中的表达及其与该腺瘤侵袭性的相关性研究

目的研究基质金属蛋白酶-9(MMP-9)、血管内皮细胞生长因子(VEGF)和p16在侵袭性和非侵袭性垂体腺瘤中的表达及其与垂体腺瘤侵袭性的相关性。方法用免疫组化方法检测MMP-9、VEGF和p16在30例侵袭性和24例非侵袭性垂体腺瘤中的表达水平,并分析其垂体腺瘤侵袭性的关系。结果 MMP-9、VEGF标记指数在侵袭性垂体腺瘤中分别为(39.44±5.61)%和(24.28±3.94)%,均较非侵袭性垂体腺瘤中的(22.17±4.32)%和(17.62±1.89)%显著增高(P0.01)。p16在非侵袭性垂体腺瘤中的标记指数为(27.49±4.07)%,较侵袭性垂体腺瘤的标记指数(20.18±3.26)%显著增高(P0.01)。垂体腺瘤的侵袭性与MMP-9和VEGF的表达呈正相关(P0.05),而与p16表达呈负相关(P0.05)。结论 MMP-9、VEGF的表达增高和p16的表达降低与垂体腺瘤的侵袭性密切相关。     

VEGF、uPA在侵袭性垂体腺瘤中的表达及意义

目的探讨血管内皮生长因子（VEGF）、尿激酶型血纤溶酶原激活剂（uPA）在侵袭性垂体腺瘤和非侵袭性垂体腺瘤中的表达及其临床意义。方法应用免疫组化法检测26例侵袭性垂体腺瘤和20例非侵袭性垂体腺瘤中VEGF、uPA的表达，并结合临床资料分析。结果VEGF和uPA在侵袭性垂体腺瘤的表达明显高于在非侵袭性垂体腺瘤中的表达，VEGF和uPA的表达水平与垂体腺瘤的侵袭性正相关。其中uPA在垂体腺瘤中的表达强度高于VEGF。结论VEGF和uPA与垂体腺瘤侵袭性生长及复发相关。     

垂体瘤血管内皮生长因子表达及其意义

目的 :探讨血管内皮生长因子在垂体瘤中的表达及其意义。方法 :应用免疫组化法对 2 0例复发、2 6例未复发的人脑垂体瘤中血管内皮生长因子表达进行检测。结果 :复发组垂体瘤中血管内皮生长因子表达较未复发组明显增高 ,两组有显著性差异 (P <0 0 1)。结论 :血管内皮生长因子在垂体瘤血管形成中起重要作用 ,可能与垂体瘤的发展与复发有关     

p16、FGFR-4及c-erbB-2的表达对垂体腺瘤生物学行为的意义

目的 探讨p16、FGFR-4及c-erbB-2表达与垂体腺瘤生物学行为的关系.方法 应用免疫组化染色检测95例乖体腺瘤p16、FGFR-4及c-erbB-2的表达水平,并对其中30例患者进行了5年随访观察.结果 垂体腺瘤p16、FGFR-4及c-erbB-2的阳性表达率分别为54.7%、98.9%和82.4%.p16表达在内分泌功能组(有功能组33例;无功能组19例)、肿瘤大小组(0级4例;Ⅰ级13例;Ⅱ级32例;Ⅲ级3例)、侵袭性组(有侵袭性3例;无侵袭性23例)以及随访组(复发1例;无复发15例)中比较差异有统计学意义(P＜0.05).FGFR-4的阳性表达与存肿瘤大小组间差异有统计学意义(P＜0.05)(0级:阳性5例、强阳性2例;Ⅰ级:阳性4例、强阳性10例;Ⅱ级:阳性12例、强阳性48例;Ⅲ级:阳性4例、强阳性9例),在侵袭组间差异无统计学意义.FGFR-4与c-erbB-2的表达呈正相天.而p16与c-erbB-2的表达呈负相关.结论 p16的表达缺失对垂体腺瘤的增殖、侵袭以及复发具有十分重要的意义:FGFR-4的过度表达对乖体腺瘤的增殖起着重要作用;FGFR-4、c-erbB-2及p16在肿瘤形成过程中可能通过相互的协同作用调控肿瘤细胞的生长周期.     

Expression of vascular endothelial growth factor in human brain tumors

Compared to normal brain an increased expression of vascular endothelial growth factor (VEGF) has been reported in many types of brain tumors. However, the numbers of samples analyzed and information about the cellular distribution of VEGF have been limited. Here we used novel monochlonal antibodies against VEGF to analyze, using immunohistochemistry, Western blotting and enzyme-linked immunosorbent assay, its expression in 108 human brain tumors that included astrocytic tumors, meningiomas, pituitary adenomas, primary intracranial germ cell tumors and neuronal tumors. The results showed that 37 of 48 astrocytic tumors (77%) and 15 of 19 meningiomas (79%) were immunoreactive for VEGF, consistent with previous reports. However, in contrast to a previous report that analyzed only VEGF mRNA; all of our 15 pituitary adenomas showed specific immunoreactivity for VEGF. We also extended the studies to previously unanalyzed neoplasms: 13 of 15 primary intracranial germ cell tumors (82%), and 7 of 10 neuronal tumors (70%) were immunoreactive for VEGF. Direct protein analysis by Western blotting confirmed the expression of VEGF in those tumors, and showed differential expression of the isoforms of VEGF protein; a pituitary adenoma expressed both VEGF₁₆₅ and VEGF₁₈₉ proteins, a central neurocytoma expressed only VEGF₁₆₅, while an immature teratoma expressed only VEGF₁₈₉. The data herein show that VEGF is expressed in a wide spectrum of brain tumors and suggest differences among tumor entities in the mechanisms of VEGF up-regulation as well as their employment of distinct VEGF isoforms for neovascularization. Received: 26 January 1998 / Revised, accepted: 15 April 1998     

垂体腺瘤的三维重建及形态特性分析

目的 通过对垂体腺瘤进行三维影像重建,探讨肿瘤形态特征及相关因素.方法 连续收集直径大于10mm的垂体腺瘤58例,其中经鼻蝶窦入路手术52例,经翼点入路手术6例;根据患者术前MRI表现,对其向蝶鞍周围扩展的程度进行分级,并运用虚拟现实技术对肿瘤进行三维模型重建及形态分类.结果 所有患者均重建了肿瘤、颈内动脉及脑组织结构.垂体腺瘤三维模型分为鞍内型（13.8％）、鞍上型（20.7％）、鞍下型（17.2％）和分叶型（48.3％）.鞍内型腺瘤均为功能型,而鞍上型、鞍下型、分叶型腺瘤中,功能型分别占75％、60％和60.7％.不同形态的肿瘤,其间质地、囊变、鞍底硬脑膜是否存在侵袭,均无统计学差异.结论 虚拟现实技术重建的垂体大腺瘤三维模型,能简单、直观地反映肿瘤与毗邻结构的空间关系,三维模型半数呈分叶状,腺瘤形态与其质地、囊变及侵袭性均无明显关系.     

垂体腺瘤囊变和囊内液平面形成的MRI特征及相关因素分析

目的探讨垂体腺瘤囊变及液平面形成的MRI特征及其临床相关因素。方法连续收集83例经手术和病理证实的垂体腺瘤，术前行MRI评估，结合手术所见和病理发现进行研究。结果MRI表现囊变者43例，其中19例无液平面的囊变区多表现为T。WI低或稍低信号，T1WI高信号；24例液平面上／下信号表现为T1WI上呈高／低信号19例，高／等信号4例，低／等信号1例；T1WI上仅7例发现液平面，其中高／等信号4例，高／略高信号2例，略低／等信号1例。垂体腺瘤囊变及液平面形成与肿瘤大小、侵袭性有关（P〈0．05），多见于泌乳素型、促性腺激素型、无功能型和多激素型腺瘤。结论垂体腺瘤囊变及液平面形成主要是因瘤内出血后，血肿衍化吸收沉淀所致。术前对垂体腺瘤囊变及液平面的MRI评估有助于对肿瘤生长方式及行为的判断。     

Hypophyseal adenoma in elderly persons. Experience with surgical treatment of 102 patients

In 1972 to 2000, a total of 102 patients aged 60 years or more underwent surgery for pituitary adenomas. They were 54 males and 48 females (mean age 63.5 years). Before surgery, all the patients had impaired vision (with asymmetry of visual loss in 61% of patients). 17% had ophthalmoplegia. Most adenomas (92%) were clinically and biochemically hormonally inactive. In all cases, pituitary adenomas had extrasellar extension: 63% of the adenomas were enclosed and 37% were invasive. A total of 111 interventions were made in 102 patients. Analyzing the outcomes indicates that transsphenoidal microsurgery is an effective and safe treatment in elderly patients with pituitary adenomas.     

垂体腺瘤中MMP-9与VEGF的表达及其与侵袭性的关系

目的探讨基质金属蛋白酶-9(MMP-9)与血管内皮生长因子(VEGF)在垂体腺瘤中的表达及其与垂体腺瘤侵袭性的关系。方法应用免疫组化染色法和逆转录聚合酶链式反应(RT-PCR)方法检测侵袭性(20例)和非侵袭性(10例)垂体腺瘤组织标本中MMP-9与VEGF的表达,分析二者与垂体腺瘤侵袭性的关系及二者的相关性。结果侵袭性垂体腺瘤组MMP-9、VEGF的蛋白及mRNA表达均较非侵袭性腺瘤组显著增高(P<0.01)。在蛋白水平,侵袭性腺瘤组中MMP-9与VEGF表达水平无显著性相关;在mRNA水平,侵袭性腺瘤组中MMP-9与VEGF表达水平成正相关(P<0.05)。结论侵袭性垂体腺瘤的生物学行为与MMP-9基因表达增高及血管生成正调节因子VEGF表达上调有关。MMP-9与VEGF在新生血管形成过程中存在着内在联系。     

侵袭性垂体腺瘤的生物学特性研究——临床、病理、细胞动力学研究

目的：深入了解侵袭性垂体腺瘤的生物学特性,以提高其诊断、治疗水平。万法：对54例病人（非侵袭性垂体腺瘤31例,侵袭性垂体腺瘤23例）的临床、病理、细胞动力学三方面资料作差异显著性检验及相关性分析。结果：在临床表现方面,两组病人在病程,肿瘤大小,肿瘤组织坏死、卒中、囊变发生率,手术全切除率,术后复发率方面有显著差异（P＜0．05）。病理学方面,两组在微血管定量方面有显著差异（P＜0．05）。细胞动力学的研究显示：侵袭性垂体腺癌的细胞增殖速率显著大于非侵袭性腺瘤（P＜0．01）。结论：侵袭性垂体腺瘤临床进展快,多为大腺瘤,肿瘤组织坏死、囊变、卒中发生率高,手术全切除率低,术后易复发,肿瘤血供较为丰富,肿瘤细胞增殖较快。     

垂体瘤经蝶入路术后常见问题的临床分析

目的:探讨垂体瘤经蝶入路术后常见问题产生的原因和处理的方法。方法:对89例经蝶入路垂体瘤患者的临床表现、术后常见问题处理等作回顾性分析。结果:34例(38．2％)术后出现暂时性尿崩;术后肿瘤残留有17例 (19．1％);16例(17．98％)术后垂体前叶功能不足;术后脑脊液漏3例(3．37％)。结论:手术中操作应轻柔,避免损伤垂体后叶和鞍隔;术后MRI早期增强扫描可发现肿瘤残留:内分泌激素水平监测是必须的,术后垂体功能低下者需激素替代治疗。     

PTTG、MMPs、VEGF在侵袭性垂体腺瘤中的表达及其意义

目的研究垂体瘤转化基因（PTTG）蛋白、基质金属蛋白酶（MMPs）和血管内皮生长因子（VEGF）在垂体腺瘤中的表达及其相关性,以及它们与垂体腺瘤生物学行为的关系。方法垂体腺瘤组织标本50例,其中侵袭性26例,非侵袭性24例,利用免疫组化Envision二步法检测并分析比较PTTG、MMP-2、MMP-9及VEGF在侵袭性垂体腺瘤和非侵袭性垂体腺瘤中的表达。结果侵袭性垂体腺瘤中PTTG、MMP-2、MMP-9及VEGF的表达均高于非侵袭性垂体腺瘤（P〈0.05）;在侵袭性垂体腺瘤中PTTG和VEGF与MMP-2、MMP-9的表达水平均呈正相关（P〈0.01）。结论垂体腺瘤的侵袭性与PTTG、MMPs、VEGF的过度表达有关,PTTG、MMPs可作为辅助诊断侵袭性垂体腺瘤的一项生物学指标。     

Recurrence of pituitary adenomas after transcranial operation.

A series of 289 pituitary adenomas operated upon transcranially have been assessed for the frequency of recurrence. Ten patients died in the postoperative period, and nine patients have been lost to follow up. Follow up data is therefore available in a series of 270 cases for a period extending up to 30 years after the initial operation. There have been 13 histologically verified recurrences (4.8%), and a further six cases are known from CT scan or air study evidence to have residual or recurrent tumour which has not necessitated re-exploration. The total recurrence or residual tumour rate could therefore be regarded as 7.4%. The large majority (77%) of recurrences have been within 10 years of the first operation, and the rest between 10 and 20 years. Histologically, all were chromophobe adenomas, and the average age of their initial presentation was lower than the peak incidence of pituitary adenoma as a whole. Two patients showed frank malignant change in the second biopsy. In recurrent tumours, most had had only subtotal excision with some macroscopic evidence of invasion or degeneration, such as cystic change, haemorrhage or necrosis. Microscopic evidence of aggressive growth and capsular invasion by tumour cells also was relatively frequent. Postoperative radiotherapy decreased and delayed recurrence, although the vast majority of cases in the series received radiotherapy. Surgery for recurrence appeared an effective method of treatment, and no patient died following repeated operation. Initial transcranial excision in more recent years using the operating microscope followed by uniform radiotherapy, appears to have considerably reduced the already small recurrence rate of pituitary adenoma.     

血管内皮生长因子及其受体表达和侵袭性垂体腺瘤血管生成关系的研究

目的研究血管内皮生长因子(VEGF)及其受体Flt-1在人垂体腺瘤中的表达,探讨其表达变化、微血管密度(MVD)与侵袭性垂体腺瘤血管生成的关系.方法采用免疫组织化学技术检测52例垂体腺瘤的VEGF及其受体表达水平,同时检测CD34表达,用于测定垂体腺瘤的MVD,比较其在侵袭性和非侵袭性垂体腺瘤中的差异.结果VEGF及其受体和MVD与垂体腺瘤的侵袭性密切相关(P＜0.01).结论VEGF可能通过促进新生血管形成刺激垂体腺瘤生长和侵袭,其作用机制有待进一步研究.     

Fluorescence histochemistry of RNA in human pituitary adenomas

Summary Acridine orange (AO)-RNA fluorescence was studied histochemically in 9 normal human pituitary glands, in 26 secretory and nonsecretory pituitary adenomas, and in a dysgerminoma. Six adenomas showing immunoreactivity for prolactin showed intense orange-red cytoplasmic fluorescence; 6 other tumours exhibiting immunoperoxidase activity of growth hormone showed less intense AO-RNA fluorescence, and 5 adrenocorticotropic hormone-containing adenomas showed still weaker orange fluorescence. Among the chromophobe adenomas without immunoreactivity for secretory products, 5 had uniformly very weak AO-RNA fluorescence, while in 4 other a few scattered cells with strong AO-RNA fluorescence were detected among the majority of weakly fluorescent cells. The pituitary dysgerminoma contained many cells with strong AO-RNA fluorescence. Electron microscopy of these cases showed good correlation of cytoplasmic concentration of ribosomes with AO-RNA fluorescence of the adenomas. AO is useful as an inexpensive, simple supplementary stain for frozen or paraffin sections of pituitary tumours to infer secretory activity as a correlate of RNA concentration and to demonstrate a secretory potential in some cells of hormonally inactive tumours.Supported by a research grant from the Alberta Children's Hospital Foundation, Calgary (HBS)     

CT findings of growth hormone secreting pituitary adenomas

The value of high-resolution computed tomography (CT) in the diagnosis of pituitary adenoma has recently been stressed, especially of the coronal view with contrast enhancement. Analysis of the CT scans of 33 growth hormone (GH) secreting pituitary adenomas was done (11 cases of microadenomas, 7 cases of intrasellar adenomas and 15 cases of macroadenomas with suprasellar extension). In macroadenomas, the density was high in five cases, high with isodense portion in two cases, mixed in four cases, isodense in three cases, and isodense and low dense in one case. Six adenomas showed homogeneous density and nine were heterogeneous. After contrast enhancement, two cases showed marked enhancement, ten cases mild and three cases ring enhancement. Margin of adenoma was smooth in nine cases and irregular in six. Among seven cases of intrasellar adenoma one accompanied primary empty sella. In microadenomas ten of eleven cases had hypodense mass inside the normally enhanced pituitary gland. The margin was ill-defined in seven cases and well-defined in three. Eight cases had pituitary height 7 mm or more. Upper surface of the pituitary gland was convex upward in five cases, flat in four and concave in two. Deviation of pituitary stalk was found in seven cases. Bony changes of sellar floor were recognized in three cases. There was a tendency that serum GH level increased with the increment of the size of adenoma. Serum GH levels in adenomas with ring enhancement were lower than those in the homogeneously enhanced adenomas of similar size. One case with marked enhancement showed the highest GH level among all adenomas of the presented series.(ABSTRACT TRUNCATED AT 250 WORDS)     

经蝶窦显微外科手术治疗开颅术后复发性垂体腺瘤

目的 探讨开颅术后残留及复发性垂体腺瘤的再次经蝶窦手术。方法 男性7例,女性9例。平均年龄49.9岁。4例为开颅术后残留性垂体腺瘤。12例为开颅术后复发性垂体腺瘤,平均复发时间为3.9年。临床表现视功能障碍14例,头痛6例,垂体功能低下4例。肿瘤1～3cm者6例,3cm以上者10例。垂体无功能腺瘤12例,泌乳素腺瘤3例,生长激素腺瘤1例。均选择经口鼻蝶窦入路再次手术。结果 肿瘤全切除7例,大部分切除6例,部分切除3例。随诊6月～5年,15例病人肿瘤未复发。结论 经额开颅术后残留及复发性垂体腺瘤可选择经蝶窦入路再次手术。     

MGMT在TSH腺瘤中的表达及临床意义

目的促甲状腺激素腺瘤(TSH腺瘤)约占垂体腺瘤总数的2%,一线的治疗方式是手术治疗,但手术治疗面临许多困难并且效果一般。有研究表明:TMZ的疗效和O-6甲基鸟嘌呤-DNA甲基转移酶(MGMT)密切相关。因此,本研究拟通过检测TSH腺瘤标本中MGMT的表达来评估TMZ对TSH腺瘤的治疗价值。方法本研究所用15例TSH腺瘤标本均来自南京军区南京总医院神经外科手术病例。采用SP免疫组织化学染色法检测15例TSH腺瘤中MGMT表达;在光镜下用半定量方法分析标本中阳性细胞核的表达情况来评分。结果本研究15例TSH腺瘤中女性8例,男性7例,平均年龄(53.2±15.9)岁。超过一半(53.3%)TSH腺瘤的MGMT表达25%,绝大多数(93.3%)TSH腺瘤的MGMT低表达(≤50%)。结论大部分TSH腺瘤低表达MGMT,可能适合TMZ治疗。     

缺氧诱导因子-1α和血管内皮生长因子与垂体腺瘤侵袭性的研究

目的研究缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）在人垂体腺瘤中的表达，探讨其表达水平与垂体腺瘤血管生成和侵袭性的关系。方法即用型免疫试剂盒检测23例垂体腺瘤中HIF-1α和VEGF的表达情况，比较两者表达的相关性；同时对表达水平与患者的临床资料进行统计学分析。结果HIF-1α和VEGF与垂体腺瘤的侵袭性密切相关（P〈0．05）。结论HIF-1α和VEGF可能通过促进新生血管形成刺激垂体腺瘤生长和侵袭，其作用机制有待进一步研究。