海锦窦侵袭性垂体腺瘤的MRI和生物学标志的临床实验研究

目的探索MRI和分子生物学标志在评价垂体腺瘤侵袭性行为中的作用。方法对45例垂体腺瘤患者术前的MRI、术中所见结果和术后组织标本免疫组化分析结果进行前瞻性研究。结果MRI预测海绵窦侵袭的敏感性60％,特异性85％,阳性预测值83％,阴性预测值63％;免疫组化分析侵袭性垂体腺瘤的MvD、Ki-67标记指数、VEGF和MMP-9表达明显高于非侵袭性垂体腺瘤(统计学分析P值分别为：<0．001、=0．039、<0．001和<0．001);但侵袭性垂体腺瘤的nm23表达却明显低于非侵袭性垂体腺瘤(P<0．001);另外,统计学分析c-myc标记指数和Bcl-2表达与垂体腺瘤的侵袭性无关(P=0．061和P=0．201)。结论增强扫描的MRI对海绵窦侵袭性垂体腺瘤的术前判断有一定参考价值;MVD、Ki-67标记指数、VEFG、MMP-9和nm23表达与垂体腺瘤的侵袭性有关。     

VEGF、Ki-67蛋白与垂体腺瘤侵袭性及复发相关性的研究

目的分析VEGF、Ki-67蛋白在垂体腺瘤中的表达,探讨VEGF、Ki-67与垂体腺瘤侵袭性与复发之间的关系。方法采用免疫组化S-P法检测上述两种蛋白在60例垂体腺瘤中的表达。结果VEGF、Ki-67在侵袭性垂体腺瘤组的阳性表达显著高于非侵袭垂体腺瘤组,复发组显著高于非复发组（P〈0．05）,VEGF与Ki-67的表达与垂体腺瘤的侵袭及复发有显著相关性（rs=0．4896 P〈0．05）。结论VEGF与Ki正7的高表达与垂体腺瘤的侵袭性与复发密切相关,VEGF和Ki-67蛋白可作为预测垂体腺瘤侵袭性及可能复发的生物学指标,也可作为指导术后个体化治疗的客观参考指标。     

垂体腺瘤质地与其生物学特性的相关性

 目的　探讨垂体腺瘤质地与其侵袭性的关系。方法　收集2008年1月至2010年1月间手术病理证实的垂体腺瘤患者76例,按磁共振成像（MRI）表现分为侵袭组（32例）和非侵袭组（44例）;按术中判断分为质地硬组（22例）和质地软组（54例）。应用免疫组织化学（SP法）检测76例垂体腺瘤标本中Ki-67和基质金属蛋白酶2（MMP-2）蛋白表达水平。分析垂体腺瘤侵袭性与Ki-67、MMP2蛋白表达的关系及垂体腺瘤侵袭性与其质地的关系。结果　侵袭组Ki-67和MMP2的蛋白表达水平分别为7.573±3.991和18.623±9.689,显著高于非侵袭组的2.811±2.095和6.871±7.230（t＝6.161、5.788,均P＜0.01）,Ki-67与MMP2表达呈正相关（r＝0.476,P＜0.01）。垂体腺瘤的侵袭性与质地无明显相关性（P＝0.056）。结论　Ki-67和MMP2可作为诊断垂体腺瘤侵袭性的分子标记物,检测Ki-67和MMP2表达水平可指导临床评价垂体腺瘤侵袭性及制定个体化治疗方案,而术前仅依靠垂体腺瘤的侵袭性并不能判断其质地。     

垂体腺瘤的血管生成、c-myc表达与侵袭性的相关意义

目的　探讨微血管密度 (microvesseldensity,MVD)、c -myc表达与肿瘤侵袭性的关系。方法　应用EnVision二步法免疫组化技术检测 5 8例垂体腺瘤的MVD、c-myc表达情况 ;分为侵袭组和非侵袭组进行统计学分析 ,并对MVD与c-myc的表达强度进行相关性分析。结果侵袭性垂体腺瘤MVD为 6 .78± 1.6 7;非侵袭性垂体腺瘤MVD为 3.72± 1.0 2 ;差异有显著性 (P <0 .0 0 1)。各型垂体腺瘤中c -myc均有表达 ,总阳性率为 37.9% ;其中侵袭性垂体腺瘤的阳性率为 5 5 .5 6 % ,非侵袭性垂体腺瘤的阳性率为 2 2 .5 8%。差异有显著性 (P <0 .0 5 ) ,侵袭性垂体腺瘤c -myc高表达。直线相关分析显示 ,c -myc表达强度与MVD呈显著正相关 (r=0 .5 5 4 ,P <0 .0 1)。结论　侵袭性垂体腺瘤MVD增高、c -myc高表达 ,是反映垂体瘤侵袭能力及预后的有用指标。侵袭性垂体腺瘤MVD与c -myc表达强度密切相关 ,提示c -myc表达强度与垂体腺瘤MVD在判定垂体腺瘤侵袭性方面有意义     

侵袭性垂体腺瘤中CD44与Ki-67表达的相关性

目的探讨细胞粘附分子CD44、细胞增值核抗原Ki-67在侵袭性垂体腺瘤中的表达及意义并探讨二者之间的关系。方法用免疫组化法检测CD44s、CD44v5、Ki-67在20例侵袭性垂体腺瘤和18例非侵袭性垂体腺瘤中的表达。结果CD44s和Ki-67在侵袭性垂体腺瘤组中表达高于非侵袭性垂体腺瘤组(P<0.01),且二者在垂体腺瘤中的表达呈正相关。CD44v5在侵袭性和非侵袭性垂体腺瘤中表达无明显差异(P>0.05)。结论CD44s和Ki-67与垂体腺瘤的侵袭性生长行为有关,二者协同作用,在侵袭性垂体腺瘤的发生、发展中起重要作用,可作为侵袭性垂体腺瘤诊断和判断预后的重要生物学指标。     

OPN、MMP-9在垂体腺瘤中的表达及与其侵袭性的关系

目的:探讨骨桥蛋白(OPN)、基质金属蛋白酶-9(MMP-9)在垂体腺瘤中的表达及与其侵袭性的关系。方法:应用免疫组化SP法检测30例垂体腺瘤标本和3例正常脑组织中OPN、MMP-9的表达。其中侵袭性垂体腺瘤17例,非侵袭性垂体腺瘤13例。结果:垂体腺瘤侵袭组OPN、MMP-9的表达水平显著高于非侵袭组(P<0.01);OPN、MMP-9与垂体腺瘤侵袭性具有相关性。结论:OPN、MMP-9可以作为评价垂体腺瘤侵袭性和预后的指标。     

垂体腺瘤p53基因Ki-67细胞增生抗原的表达及其临床意义

目的探讨垂体腺瘤p53基因和Ki-67细胞增生抗原表达的变化与肿瘤侵袭行为、肿瘤复发的相关性。方法经手术切除的垂体腺瘤标本67例,按影像学显示的肿瘤大小分为A,B两组(<2.5cm为A组,>2.5cm为B组),用免疫组化方法分别检测p35基因与Ki-67的表达,临床随访1￣3年,观察肿瘤复发情况。结果A组39例中p53阴性11例,低表达28例,Ki-67均为低表达,3年内肿瘤复发4例;B组26例(达到侵袭性标准),p53均显示高表达,Ki-67中度表达10例,高表达16例,其中11例肿瘤3年内复发,两组比较有显著差异(P<0.05)。结论垂体腺瘤的p53和Ki-67的表达与肿瘤的侵袭性呈正相关,而Ki-67的高表达还与肿瘤的复发有关。     

垂体腺癌组织的超微结构及其血管内皮生长因子和基质金属蛋白酶9的表达意义

目的探讨垂体腺癌组织的超微结构及其血管内皮生长因子(VEGF)和基质金属蛋白酶9(MMP-9)的表达意义。方法选取2007年1月至2014年1月间收治的116例垂体腺瘤患者。采用免疫组化染色法和逆转录聚合酶链式反应检测垂体腺瘤组织中VEGF和MMP-9的表达情况,电子显微镜下观察垂体腺瘤的超微结构,并结合VEGF和MMP-9的表达对垂体腺瘤患者的侵袭性进行分析。结果电镜下,侵袭性垂体腺瘤可见较多的粗面内质网、形态怪异的胞核、丰富的核糖体及较大的核仁;非侵袭性垂体腺瘤的核异形率、核仁出现率、线粒体数目和核浆比例均低于侵袭性垂体腺瘤,差异有统计学意义(P<0.05)。非侵袭性垂体腺瘤患者的VEGF、MMP-9蛋白和mRNA表达均低于侵袭性垂体腺瘤患者,差异有统计学意义(P<0.05)。侵袭性垂体腺瘤组患者的VEGF和MMP-9蛋白表达水平无显著差异,但在mRNA水平上呈正相关(r=0.463,P<0.05)。结论电镜观察结果和免疫组化结果均显示侵袭性垂体腺瘤患者的超微结构和侵袭性生长有一定的相关性,且VEGF和MMP-9与新生血管的形成有一定的联系。     

侵袭性垂体腺瘤中Fascin蛋白、MMP-2和MMP-9的表达与研究

目的：垂体腺瘤侵袭性生长的机制还不清楚。本研究旨在检测肌动蛋白结合蛋白（Fascin）及基质金属蛋白酶-2（matrixmetallopmteinasesMMP-2）和基质金属蛋白酶-9（matrix metalloproteinasesMMP-9）在侵袭性垂体腺瘤中的表达水平,分析其与垂体腺瘤的生长侵袭性之间的可能关系。方法：免疫组织化学SP法检测三者在72例垂体腺瘤（侵袭性27例,非侵袭性45例）中的表达水平,统计学分析三者在垂体腺瘤中表达差异性．及与不同临床特征的表达相关性。结果：Fascin蛋白、MMP-2及MMP-9在侵袭性垂体腺瘤的表达水平高于非侵袭性垂体腺瘤（t=3．03,t=3．33,t=2．02,P〈0．05）。三者在垂体腺瘤中表达水平与患者性别无明显相关．与肿瘤有无分泌功能无明显相关,但与肿瘤大小有关铲值分别为8．53,11-31,12．46,P〈0．05）。结论：Fascin蛋白、MMP-2及MMP-9在侵袭性垂体腺瘤中高表达,提示三者可能与垂体腺瘤侵袭性生长密切相关．     

胶质瘤组织中整合素β1及Ki-67表达的临床意义

目的探讨胶质瘤中整合素β1及Ki-67的表达及其临床意义.方法应用免疫组化方法检测45例胶质瘤、5例正常脑组织中整合素β1及Ki-67的表达.结果在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中,整合素β1的阳性表达率分别为42.11%(8/19)及73.08%(19/26),差异有统计学意义,χ2=4.388,P=0.036;Ki-67标记指数分别为(7.06±4.17)%和(13.45±8.69)%,差异有统计学意义,t=3.269,P=0.002;且整合素β1的表达与Ki-67标记指数具有正相关关系,r=0.71,P=0.000.结论整合素β1表达上调能促进胶质瘤细胞的增殖及侵袭;整合素β1与Ki-67的表达均可应用于临床,作为评价胶质瘤恶性程度、选择治疗措施及预测患者预后等的重要指标.     

Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space

Summary The preoperative diagnosis of cavernous sinus invasion remains difficult and controversial, and there are currently no reliable histological or molecular markers that predict pituitary tumour behaviour and response to treatment. We evaluated 45 patients with pituitary adenoma. The results have shown that the sensitivity of MRI for indicating cavernous sinus invasion in this prospective study was 60%, specificity 85%, positive predictive value 83.33%, negative predictive value 62.96%. Forty-five specimens of pituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, bcl-2, nm23 and MMP-9 immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. The results have shown that MVD of invasive pituitary adenomas was significantly higher than that of noninvasive (P < 0.001). There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P < 0.001) and MMP-9 (P < 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs. P = 0.201). On the other hand, there is an inverse relationship between nm23 expression and tumor invasion (P < 0.001). In conclusion, parasellar extension of pituitary adenomas through the medial wall of the cavernous sinus diagnosed at surgery, can be determined by radiology with sensitive gadolinium-enhanced MRI. Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity. These markers can only provide some useful informations on the therapeutic strategy of pituitary adenomas.     

膀胱移行细胞癌的CT表现与Ki-67、VEGF和MVD表达的相关性

[目的]探讨膀胱移行细胞癌（BTCC）的CT表现与Ki-67、血管内皮生长因子（VEGF）和微血管密度（MVD）表达的关系。[方法]对41例经手术病理证实的BTCC，采用LDP免疫组化法，检测肿瘤标本中Ki-67、VEGF和MVD的表达，并分析其与术前CT征象的关系。[结果]Ki-67LI与VEGF、Ki-67LI与MVD、VEGF与MVD呈显著性正相关（r值分别为0．548、0．603、0．705，P均〈0．001）。Ki-67LI、VEGF和MVD表达与肿瘤呈分叶状、肿瘤多发、膀胱壁增厚、浆膜受侵、邻近器官受累等CT征象均有关（P〈0．05）。[结论]BTCC的CT征象与Ki-67LI、VEGF和MVD表达密切相关，当肿瘤有分叶征、肿瘤多发、相邻膀胱壁增厚、浆膜层受侵、邻近器官受累等CT征象时，提示肿瘤可能有较高的恶性程度、浸润能力及较差的预后。     

Adrenocorticotropic hormone secreting pituitary adenomas: analysis of growth fraction using the MIB-1 antibody

AIMS AND BACKGROUND: Pituitary adenomas are usually considered well differentiated tumors, even if in about one third of cases they invade surrounding tissues, with the possibility of postoperative relapse after complete surgical removal. Adrenocorticotropic hormone (ACTH) secreting adenomas seem to be the most infiltrating subtype, with a higher incidence of recurrence. Ki-67 is a nuclear antigen which is easily detectable by means of the MIB-1 monoclonal antibody, and the labeling index (LI) obtained can be considered a marker of tumor proliferation. METHODS: In order to identify the growth fraction of these tumors we used the MIB-1 antibody to evaluate the expression of Ki-67 antibody in 11 ACTH secreting pituitary adenomas and to compare it with the LI obtained in 98 other hormone secreting or non-functioning pituitary adenomas consecutively operated on during a 40-month period. RESULTS: In relation to surgically verified infiltration of the sellar floor dura and bone, we identified eight non-invasive and three invasive ACTH secreting pituitary adenomas. All invasive tumors infiltrated the wall of the cavernous sinus (CS). The mean Ki-67 LI was 5.88 +/- 9.13% versus 2.33 +/- 2.40% in non-ACTH secreting adenomas (P = 0.0025). It was 13.27 +/- 15.42% in invasive and 3.11 +/- 4.37% in non-invasive ACTH adenomas, and 18.40 +/- 17.82% in patients over 50 years versus 3.10 +/- 4.09% in younger subjects (P = 0.02). CONCLUSIONS: Ki-67 LI is a useful marker in the determination of proliferative activity and invasiveness of anterior pituitary adenomas. Our data seem to confirm that ACTH secreting adenomas have a higher growth fraction than other pituitary adenomas and this observation presumably explains the higher incidence of relapse of these tumors even after macroscopically total removal.     

Expression of hepatocyte growth factor and its receptor c-Met in human pituitary adenomas

Hepatocyte growth factor (HGF) and its receptor c-Met have been known as key determinants of growth and angiogenesis in some brain tumors like gliomas, meningiomas, and schwannomas. But little is known about their expression in pituitary adenomas. In this study, the expression of HGF and c-Met in pituitary adenomas of different histology types was investigated by immunohistochemistry, and correlative analysis of their expression with microvessel density (MVD), Ki-67 expression, and other clinicopathologic factors was made. The results showed that the expression of HGF and c-Met exists in 98% (64 of 65) and 92% (60 of 65) pituitary adenomas, respectively, and co-expression of them existed in 91% (59 of 65) adenomas. HGF had significant correlation with MVD (Spearman''s correlation coefficient, r = .31, P = .01) and Ki-67 (r = .32, P = .01). c-Met had significant correlation with MVD (r = .30, P = .02) and Ki-67 (r = .38, P = .00). HGF and c-Met expression had no significant correlation with age or extrasellar extension. There were no significant differences in HGF and c-Met expression between pituitary adenomas of different histology types. The results indicate that HGF and c-Met are widely expressed in pituitary adenomas, and their expression correlates with MVD and Ki-67 expression.     

VEGF及其受体KDR在垂体腺瘤中的表达与肿瘤血管形成的关系

 目的　探讨血管内皮生长因子(VEGF) 及其受体( KDR) 的表达与垂体腺瘤血管生成的关系。方法　应用免疫组织化学S2P 法检测58 例人垂体腺瘤中的V E GF 及KD R 的表达,并对血管进行染色、计数。结果　其中54 例有VEGF 的表达(占93. 1 %) ,阳性表达主要位于肿瘤细胞胞膜及胞浆; KD R 在47 例中有阳性表达(占81. 0 %) ,阳性表达位于肿瘤血管内皮细胞、肿瘤细胞胞膜及胞浆。VEGF 和KD R 表达与垂体腺瘤的侵袭性密切相关;V E GF 和KD R 高表达组微血管密度明显高于低表达组( P <0. 01) 。结论　VEGF 以旁分泌、自分泌形式协同KDR 促进垂体腺瘤血管的生成,并与垂体腺瘤的侵袭密切相关。     

宫颈癌MMP-9表达与肿瘤血管生成、癌细胞增殖及侵袭转移的关系

背景和目的：基质金属蛋白酶－9（matrix metalloproteinase-9,MMP-9）在肿瘤血管生成及肿瘤侵袭转移过程中起重要调节作用。本研究探讨MMP－9在早期宫颈癌的表达和临床意义。方法：采用免疫组织化学SP法检测75例早期宫颈浸润癌（invasive carcinoma of cervix,ICC）、18例宫颈上皮内瘤样病变（cervical intraepithelial neoplasm,CIN)和15例正常宫颈上皮（normal cervical epithelium,NCE）中MMP－9的表达情况,并检测其微血管密度（microvessel density,MVD)(CD34标记）和癌细胞增殖标记指数（Ki-67标记）。结果：在宫颈癌中,MMP－9主要表达于癌细胞膜和／或细胞浆;Ki-67主要表达于癌细胞核;CD34主要表达于间质血管内皮细胞。从正常宫颈上皮到宫颈上皮内瘤样病变再到宫颈浸润癌,MMP－9、Ki-67的阳性表达率和MVD均逐步显著升高（P＜0．05）。MMP－9在ICC中表达与MVD显著正相关（γ=0.287,P＜0．05）。MMP－9在ICC中表达与盆腔淋巴结转移、脉管浸润、间质浸润、FIGO分期、组织学分级和Ki-67表达有关（P＜0．05或P＜0．01）;而与年龄和组织学类型无关（P＞0．05）。有盆腔淋巴结转移、脉管浸润、突破深层间质浸润、FIGO分期为Ⅱ期、组织学分级为Ⅲ级及Ki-67高度表达者,其MMP－9阳性表达率分别显著高于无盆腔淋巴结转移、无脉管浸润、浸润深度在浅层间质以内、FIGO分期为I期、组织学分级未超过Ⅱ级及Ki-67表达在中度以内者（P＜0．01或P＜0．05）。结论：MMP－9阳性表达可能在宫颈癌血管生成、癌细胞增殖和侵袭转移中起重要作用。MMP－9过度表达者,宫颈癌血管生成能力显著增强、癌细胞增殖活跃、更易发生侵袭转移,但并非惟一决定因素。检测宫颈癌中MMP－9表达对进一步了解宫颈癌生物学行为和判断其预后有一定的价值。     

Expression of epithelial cadherin and cavernous sinus invasion in human pituitary adenomas

Pituitary adenomas generally are regarded as benign tumors,although some invade the cavernous sinus and recur.We examined the epithelial cadherin (E-CD) expression in30 pituitary adenomas (6 with cavernous sinus invasionand 24 without). Immunoreactivity of E-CD were foundin all pituitary adenomas but they were veryvarious. The presence of an association between E-CDexpression and cavernous sinus invasion was assessed. Therewere no significant differences in E-CD expression betweeninvasive and noninvasive adenomas. These results suggest thatE-CD expression is not associated with cavernous sinusinvasion in pituitary adenomas.     

垂体腺瘤细胞增殖活性和肿瘤生长方式的相关性研究

目的　探讨垂体腺瘤细胞增殖活性和其侵袭性生长方式之间的相关性。方法　采用单克隆抗体MIB -1免疫组织化学染色 ,确定 110例垂体瘤的Ki -67标记指数。结果　平均标记指数是 2 65 %。患者年龄、肿瘤大小对标记指数无影响。非侵袭组是2 0 1% ,侵袭组是 3 71% ,P =0 0 2 7,有显著性差异。侵袭蝶窦组是 5 5 8%。功能性腺瘤是 3 0 9% ,非功能性腺瘤是 1 98% ,P =0 14 ,两者之间无显著性差异。ACTH腺瘤的标记指数是 5 47% ,其他功能性腺瘤是 2 3 3 % ,P =0 0 1,有显著性差异。患者年龄、肿瘤大小对标记指数无影响。结论　肿瘤细胞的增殖活性与垂体瘤的侵袭性生长有关 ,但不是肿瘤发生侵袭的唯一因素