基质金属蛋白酶-2在侵袭性垂体腺瘤中的表达

目的　探讨基质金属蛋白酶 2 (matrixmetalloproteinase 2 ,MMP 2 )的表达与侵袭性垂体腺瘤的关系。方法　用免疫组化的方法对 5 4例垂体瘤患者组织标本中MMP 2的表达进行检测。并对其中 16例患者采用逆转录 聚合酶链反应 (RT PCR)的方法检测了MMP 2mRNA的表达。免疫组化结果用半定量的方法进行分析。结果　 5 4例垂体瘤患者中 ,有 32例女性 ,2 2例男性。其中 ,12例为侵袭性垂体腺瘤 ,4 2例为非侵袭性垂体腺瘤。免疫组化显示 ,侵袭性垂体腺瘤的MMP 2的表达明显高于非侵袭性垂体腺瘤 (分别为 4 .3± 0 .5 ;2 .3± 0 .2 ;P <0 .0 1)。大型垂体腺瘤和微垂体腺瘤 ,以及功能性和非功能性垂体腺瘤的MMP 2的表达则无明显差别。MMP 2的表达与Ki 6 7的表达无明显相关性 (r =$C 0 .0 5 ,P >0 .0 5 )。侵袭性垂体腺瘤MMP 2mRNA的表达 ,明显高于非侵袭性垂体腺瘤 (6 8.3± 15 .3;2 1.8± 8.2 ;P <0 .0 5 )。结论　MMP 2的高表达与肿瘤的侵袭性密切相关。但与肿瘤的大小及分泌功能无明显关系。MMP 2可以作为肿瘤侵袭性一项有效的指标     

基质金属蛋白酶表达和MVD计数与垂体腺瘤侵袭性的关系研究

目的研究基质金属蛋白酶表达和微血管密度(MVD)计数与垂体腺瘤侵袭性相关性。方法选取垂体腺瘤手术标本41例,分为侵袭组(18例)和非侵袭组(23例)。采用免疫组化法检测MMP-2在两组中的表达水平,并计数垂体腺瘤组织中MVD。结果MMP-2在侵袭组和非侵袭组表达阳性率分别为72.2%(13/18)、26.1%(6/23),两组比较有显著性差异(P<0.05);MVD计数在侵袭组和非侵袭组分别为50.51、13.41,两组比较有显著性差异(P<0.05);侵袭性垂体腺瘤中MMP-2的表达水平与MVD计数呈正相关(P=0.000)。结论MMP-2和MVD表达与垂体腺瘤侵袭性密切相关。     

侵袭性垂体腺瘤侵袭性的综合判断及其与临床预后的关系

目的分析经侵袭性垂体腺瘤侵袭性的判断标准及其与临床预后的关系。方法回顾性分析我科自2000年1月至2003年5月行经蝶手术切除的具有完整影像学、病理学和随访资料的侵袭性垂体腺瘤82例,随访时间5～30个月。结果侵袭性垂体腺瘤MR影像学特点为鞍底受侵下陷,部分肿瘤突入蝶窦;颈内动脉包绕;海绵窦受累,鞍隔突破等。病理检查以鞍底硬膜浸润的发生率最高。PRL腺瘤的全切率明显低于无功能腺瘤(P<0.01),无功能腺瘤、GH腺瘤与ACTH腺瘤之间相差不明显。PRL腺瘤的复发率较无功能腺瘤和GH腺瘤高(P<0.05)。结论垂体腺瘤的侵袭性生物学行为导致手术全切几率下降,是术后复发的主要原因。     

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。     

MMP-2-PEX与MMP-2在侵袭性垂体腺瘤中的表达及意义

目的研究基质金属蛋白酶-2在C端的血红素样结构域(MMP-2-PEX)和基质金属蛋白酶-2(MMP-2)在侵袭性垂体腺瘤中的表达及其意义。方法用逆转录酶-聚合酶链反应(RT-PCR)法检测116例垂体腺瘤标本的MMP-2-PEX及MMP-2的表达,分析其与侵袭性垂体腺瘤的关系及两者之间的相关性。结果侵袭性垂体腺瘤组MMP-2-PEX mRNA表达较非侵袭性垂体腺瘤组显著降低(P<0.01)。侵袭性垂体腺瘤组的MMP-2 mRNA表达明显高于非侵袭性垂体腺瘤组(P<0.01)。侵袭性垂体腺瘤组中MMP-2-PEX mRNA表达与MMP-2 mRNA表达呈负相关(r=-0.66,P<0.05),而非侵袭性腺垂体腺瘤组中无相关性(r=-0.22,P>0.05)。结论 MMP-2-PEX低表达及MMP-2高表达与垂体腺瘤的侵袭性密切相关,MMP-2-PEX及MMP-2可以作为垂体腺瘤侵袭性的重要参考指标。     

微血管密度及血管内皮生长因子表达与垂体瘤侵袭性的关系

目的探索垂体瘤微循环与侵袭性的关系及其临床意义。方法采用免疫组化技术检测了42例垂体瘤中血管内皮生长因子(VEGF)蛋白表达,同时染色VonWillebrand因子显示血管内皮细胞以检测肿瘤内微血管密度MVD,分析VEGF蛋白表达及MVD与垂体瘤海绵窦侵袭性的关系。结果VEGF蛋白表达和MVD与垂体瘤的海绵窦侵袭性均有关(两者均P<0.001)。结论VEGF与新生血管形成在垂体瘤的侵袭性生物学行为中具有重要的作用。     

Surgical treatment of invasive pituitary adenomas (somatotropinoma or corticotropinoma)

AIM OF THE STUDY: To evaluate efficiency of the transcranial epidural approach in the treatment of invasive GH- or ACTH-secreting pituitary adenomas with extension to the cavernous sinus. MATERIAL AND METHODS: During the past two years (from January 2000 to December 2001) 14 patients with invasive GH- or ACTH-secreting pituitary adenomas extending to the cavernous sinus were operated on using the transcranial epidural approach. Our experience is based on an analysis of 12 patients with GH-secreting tumors and 2 patients with ACTH-secreting adenomas. The patients' mean age was 45.36 years (range 28-66, SD +/- 10.26 years). Parasellar extension of the tumor was measured using the Knosp scale--in all the cases there was an extension to the cavernous sinus, in stage III (4 patients) or stage IV (10 patients). RESULTS: In none of the cases a total surgical removal of the invasive GH-secreting adenoma was attained (according the following cure criteria: basal serum GH level below 2.5 micrograms/l, OGTT < 1 microgram/l, normal sex- and age-related IGF-I level). In four patients the surgery resulted in a reduction of the basal serum GH level to below 5 micrograms/l (their postoperative mean serum IGF-I level was 530 micrograms/l--significantly lower, but still abnormal, p < 0.05). In a single case of a female patient the basal serum GH level was below 10 micrograms/l, while in other 7 patients the GH level remained above 10 micrograms/l. Remission (normalization of 24-hour urine-free cortisol (UFC) and its metabolites) was achieved in one patient with the Cushing disease. There were no complications involving case fatality. A transient deterioration of the third cranial nerve function observed in one patient disappeared within 3 months from the surgery. There was no deterioration of pituitary function and no cases of diabetes insipidus in our group. CONCLUSION: Transcranial epidural approach is an alternative to radiotherapy and/or prolonged medication in the treatment of invasive GH- or ACTH-secreting pituitary adenomas.     

Ki-67、MMP-9蛋白表达与垂体腺瘤侵袭性的相关性研究

目的 检测细胞核内增殖抗原Ki-67与基质金属蛋白酶-9(MMP-9)在侵袭性、非侵袭性及复发垂体腺瘤中的表达,探讨其与垂体腺瘤侵袭性及肿瘤复发的相关性.方法 免疫组化SP法对86例垂体腺瘤患者标本的Ki-67、MMP-9的表达进行检测.结果 侵袭性垂体腺瘤的Ki-67、MMP-9蛋白表达明显高于非侵袭性垂体腺瘤(P＜0.01);侵袭性腺瘤复发组Ki-67、MMP-9蛋白表达明显高于侵袭性腺瘤非复发组(P＜0.01),且Ki-67、MMP-9蛋白在垂体腺瘤中表达呈正相关.结论 Ki-67、MMP-9蛋白表达增高与侵袭性垂体腺瘤的发生及术后复发存在相关性,且两者在垂体腺瘤的侵袭性生长中可能起协同作用.     

Ki—67抗原在侵袭性垂体腺瘤中的表达研究

目的 探讨垂体腺瘤中Ki—67抗原表达与垂体腺瘤侵袭性的关系。方法 采用新一代鼠抗人Ki—67单克隆抗体MIB—1免疫组化LSAB法对52例侵袭性垂体腺瘤和35例非侵袭性垂体腺瘤中的Ki—67抗原表达进行检测，以MIB—1增殖细胞指数(MIB—1PCI)表示。结果 侵袭性垂体腺瘤和非侵袭性垂体腺瘤间、海绵窦侵袭腺瘤和无海绵窦侵袭腺瘤间，Ki—67抗原表达有显性差异。结论 Ki—67抗原表达可以作为反映垂体腺瘤增殖潜能、侵袭性和侵袭程度的标志物，具有较大的临床应用价值。     

GGF、PCNA与垂体瘤侵袭性关系探讨

目的：探讨胶质生长因子（GGF）、增殖细胞核抗原（PCNA）与人垂体腺瘤侵袭性生长的关系。对垂体瘤生长的生化机制作进一步探讨,并对术后生长作预测。方法：免疫组织化学方法分析GGF、PCNA在147例垂体瘤中的表达,分析GGF、PCNA的表达与垂体腺瘤侵袭性关系。用GGF干预垂体瘤细胞,观察细胞生长、细胞周期变化情况。结果：GGF、PCNA在多数侵袭性垂体瘤阳性表达,侵袭性垂体腺瘤中GGF表达显著大于非侵袭性腺瘤（P〈0.05）;复发组GGF、PCNA表达明显高于非复发组（P〈0.05）。结论：GGF可以明显促进垂体瘤细胞生长,与其侵袭性有重要作用。GGF、PCNA能够部分地反映垂体腺瘤细胞的增殖状态及侵袭潜能,可为临床上评价垂体腺瘤侵袭性、复发、治疗及预后提供参考。     

基质金属蛋白酶—2和9在垂体腺瘤中的表达

目的探讨基质金属蛋白酶-2(MMP-2)和9(MMP-9)的蛋白表达与垂体腺瘤侵袭性的关系。方法采用免疫组化S-P法检测8例正常垂体前叶组织、20例非侵袭性和31例侵袭性垂体腺瘤组织中MMP-2和MMP-9的表达。结果MMP-2在正常垂体前叶组织、非侵袭性垂体腺瘤和侵袭性垂体腺瘤中均有表达,且依次呈现增高趋势,但差别无统计学意义(P>0.05)。MMP-9在侵袭性垂体腺瘤中的表达强度明显高于非侵袭性垂体腺瘤和正常垂体前叶组织(P<0.05)。MMP-2和MMP-9在功能性垂体腺瘤中的表达高于非功能性垂体腺瘤,但差别无统计学意义(P>0.05)。结论垂体腺瘤的侵袭性与MMP-9的异常高表达有关,MMP-9的高表达可能作为临床评价垂体腺瘤侵袭性的参考指标。     

Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue

Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). Serine proteases have not yet been investigated in human pituitary adenomas. In this study, paraffin-embedded material from 84 human pituitary adenomas (acromegaly n=18, Cushing's disease n=21, prolactinoma n=18, thyroid-stimulating hormone-secreting adenoma n=1, nonsecreting adenoma n=26) and 9 nontumourous anterior pituitary lobes (obtained from patients with prostate cancer) was immunohistochemically analysed for expression of MMP-2, MMP-9, tissue inhibitor of metalloproteinases-2 (TIMP-2), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and interleukin-6 (IL-6). Cavernous sinus invasion was determined by assessment of preoperative magnetic resonance imaging and intraoperative inspection (invasive n=50, noninvasive n=34). In pituitary adenomas, reactions were positive (diffuse expression) to MMP-2 (74% of cases), MMP-9 (49%), TIMP-2 (88%), uPA (89%), uPAR (90%), tPA (69%), and PAI-1 (87%). A weak expression of IL-6 was found in 12% of the adenomas. All reactions were positive (focal expression) in every sample of anterior lobe tissue, except for uPA (negative in 3 out of 9 cases), and IL-6 (faintly positive in 5 out of 8 cases). Adenomas showed remarkably greater expression of uPA than anterior lobe tissue (Chi-square P<0.05). Nonsecreting adenomas exhibited a stronger tendency towards overexpression of uPA in invasive tumours when compared to noninvasive adenomas (Chi-square P=0.053). We found no correlation of MMP-9 expression and tumour invasion. TIMP-2 was overexpressed in noninvasive as compared to invasive adenomas (Chi-square P<0.05). The interrelationship between MMPs and serine proteinases in pituitary adenomas remains to be elucidated. From our data, a correlation between IL-6 and an activation of MMP-9 cannot be proven. The uPA-system may, however, play a role in dural invasion of pituitary adenomas.     

转录因子YY1对垂体瘤侵袭性的影响

目的观察转录因子YY1(Yin-Yang 1)在垂体腺瘤中的表达情况,并进一步分析沉默YY1对大鼠垂体瘤GH3细胞侵袭性的影响。方法运用免疫组化技术观察YY1在不同类型垂体腺瘤组织中的表达情况。Western blot实验检测siRNA沉默大鼠垂体瘤GH3细胞中的基因YY1后,YY1蛋白及基质金属蛋白酶MMP-2、MMP-9的表达水平。采用Transwell chamber细胞侵袭实验观察沉默YY1对GH3细胞侵袭的影响。结果 YY1在侵袭性垂体腺瘤中表达升高;沉默YY1后,GH3细胞侵袭能力下降35.7%(P0.05),MMP-2、MMP-9蛋白表达量下降(P0.05)。结论转录因子YY1在侵袭性垂体腺瘤中的表达升高,并通过上调MMP-2、MMP-9的表达来促进GH3细胞侵袭性。     

Nucleostemin和Ki-67在垂体腺瘤组织中的表达及其临床意义

目的 研究nucleostemin基因和Ki-67抗原在垂体腺瘤中的表达,分析nucleostemin基因在垂体腺瘤细胞增殖及肿瘤发生和发展中的作用. 方法 收集垂体腺瘤手术标本71例,采用半定量RT-PCR方法检测垂体腺瘤标本中nucleostemin mRNA的表达情况,采用免疫组化方法检测垂体腺瘤石蜡切片中Ki-67抗原的表达情况.同时收集相关临床资料. 结果 本组71例垂体腺瘤手术标本均有nucleostemin mRNA表达.非侵袭性垂体腺瘤和侵袭性垂体腺瘤中nucleostemin mRNA、Ki-67标记指数(Ki-67LI)表达差异有统计学意义(P＜0.05).复发组与未复发组中Ki-67LI表达差异有统计学意义(P＜0.05).Nucleostemin mRNA表达水平与Ki-67LI呈正相关关系(r=0.237,P＜0.05). 结论 Nucleostemin基因在人垂体腺瘤的侵袭性行为中发挥重要作用,其表达增高和Ki-67表达水平升高之间存在正相关,二者可以作为判断垂体腺瘤侵袭性和预测复发的有效临床检测指标.     

垂体腺瘤的侵袭与CD147、Galectin-3及微血管密度表达的关系

目的 检测CD147、Galeetin-3及微血管密度(MVD)在侵袭性和非侵袭性垂体腺瘤中的表达,以探讨其与垂体腺瘤MRI侵袭特征的关系.方法 对34例垂体腺瘤患者术前行MRI检查,术后收集标本应用免疫组化sP法检测垂体腺瘤标本中CD147、Galeetin-3及MVD的表达,分析MRI侵袭性表现与CD147、Galecfin-3及MVD表达之间的关系.结果 在垂体腺瘤相关MRI侵袭征象中,肿瘤超过外切线、海绵窦段颈内动脉被肿瘤包绕>50%、蝶窦侵犯、肿瘤形态不规则及双侧颈内动脉的不对称性均与CD147及Galectin-3的表达有关(P<0.05),肿瘤囊变坏死及瘤卒中与CD147及Galectin-3表达无关(P>0.05).结论 CD147及Galectin-3的高表达与垂体腺瘤MRI侵袭特征密切相关,CD147和Galectin-3可以作为垂体腺瘤侵袭性的分子标记物.     

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。     

Significance of leptin expression in invasive potential of pituitary adenomas

We immunohistochemically examined the expression of leptin in pituitary adenomas to investigate the correlation between the invasiveness of tumours and leptin expression. The subjects consisted of 79 patients with pituitary adenoma and were classified into the following groups: (1) non-functioning adenomas; (2) GH-secreting adenomas; (3) prolactinomas; (4) ACTH-secreting adenomas; (5) others (LH, FSH or TSH-secreting adenomas). Thereafter all cases were subdivided according to the size of tumour and the presence of invasion to the surrounding tissue. Among non-functioning adenomas, there was no significant difference between invasive and non-invasive non-functioning adenoma. In functioning adenomas, a significant difference in leptin expression was noted in intrasellar non-invasive adenomas compared to other adenomas. There was also a significant difference in leptin expression between non-invasive and invasive adenomas regardless of size. These results suggest that leptin has a role in the invasive potential of functioning adenomas.     

LRIG2蛋白表达与人垂体腺瘤侵袭性的研究

目的探索研究LRIG2蛋白表达水平与人垂体腺瘤侵袭性的相关性。方法采用免疫组织化学染色法检测159例垂体标本（8例正常人垂体标本,151例人垂体腺瘤标本）中LRIG2和MMP-9的表达水平,并进行相关性分析。结果LRIG2、在正常人垂体中无阳性反应,LRIG2蛋白表达水平在侵袭性垂体腺瘤比非侵袭性垂体腺瘤显著增高（P〈0.001）,且LRIG2蛋白与MMP-9的表达水平呈正相关（r=0.698,P〈00.001）。结论LRIG2可能作为一个新的垂体腺瘤侵袭性预测指标,检测LRIG2表达水平可指导临床评价垂体腺瘤的侵袭性及制定个体化治疗方案。     

儿童及青少年垂体腺瘤临床病理特征及MMP-9的表达意义

目的研究儿童及青少年垂体腺瘤的临床病理特征及MMP-9表达与肿瘤侵袭性的相关性。方法分析53例儿童及青少年垂体腺瘤的临床特征、形态学特征及MMP-9的表达情况。结果31例大腺瘤中,侵袭性16例,占51.6%;12例巨腺瘤中,侵袭性9例,占75.0%;而10例微腺瘤中仅2例有侵袭性,占20.0%。形态学显示:核分裂相Ⅱ级21例,核仁显著24例,瘤巨细胞28例。肿瘤形态学特征、内分泌类型与肿瘤侵袭性无显著相关性(P0.05)。27例侵袭性腺瘤中(侵袭组),MMP-9表达20例,占74.1%;26例非侵袭腺瘤中(非侵袭组),MMP-9表达12例,占46.2%;两组比较,差异有统计学意义(P0.05)。37例获随访,放疗组(11例)术后复发5例,平均53.3个月复发;未放疗组(26例)复发7例,平均19.4个月复发。结论儿童与青少年垂体腺瘤形态学特征与肿瘤侵袭性无显著相关,与肿瘤大小有关,而MMP-9可能参与垂体腺瘤侵袭性的发生。     

Pituitary volume and headache: size is not everything

BACKGROUND: Pituitary tumors are commonly associated with disabling headache. The accepted mechanisms for headache are dural stretch and cavernous sinus invasion. OBJECTIVE: To determine if there is a relationship between pituitary tumor size and the report of headache. DESIGN: We prospectively studied 63 patients who were initially seen with pituitary tumors. Clinical headache scores, pituitary tumor volume, and the extent of cavernous sinus invasion were obtained for each patient. RESULTS: The prevalence of headache was 70%. There was no positive correlation the between clinical headache score and pituitary volume (r = -0.32, P =.01, Spearman rank correlation). There was also no association between cavernous sinus invasion and headache. There was a strong association between pituitary-associated headache and a family history of headache (chi(2) = 8.36, P =.004). CONCLUSIONS: These data suggest that a pituitary tumor-associated headache may not simply be a structural problem. Other factors such as family history of headache, and the endocrine activity of the tumor may be equally important determinants of headache. Elucidating these mechanisms will aid in the treatment of these patients and further our understanding of other headache syndromes.