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2．01％，侵袭组是3．71％，P＝0．027，有显著性差异。侵袭蝶窦组是5．58％。功能性腺瘤是3．09％，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2．33％，P＝0．01，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有关，但不是肿瘤发生侵袭的唯一因素。     

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     

501例垂体瘤患者临床特征及预后分析

摘 要： ［目的］ 探讨垂体瘤患者的临床特征和预后分析。［方法］ 对2006年1月至2015年12月就诊于襄阳市中心医院的501例垂体瘤术后患者的临床资料进行回顾性分析。［结果］ 男性患者的发病年龄明显高于女性（46.7±13.2岁 vs 45.0±12.5岁;t=2.994,P=0.003）。肿瘤大小0.5~8.0cm。其中大腺瘤最为多见(86.0%),其次为巨大腺瘤 (8.6%),而微腺瘤的检出率仅为5.4%;不同影像学检查方法与不同大小垂体瘤检出率之间差异有统计学意义(χ2=7.085,P=0.029)。MRI对微腺瘤的检出率(77.8%)高于CT的检出率(22.2%)。垂体瘤临床症状以头晕、头痛及呕吐为主(46.1%),其次为视力下降、视物模糊、视野缺损(35.7%)。术前诊断以多激素混合瘤最多 (60.1%),其次为促甲状腺激素瘤(TSH) (16.6%),促性腺激素瘤(LH/FSH)最低(0.6%),术后病理诊断以泌乳素瘤(PRL)最多(33.1%),其次为多激素混合瘤(21.6%)。生存分析结果显示,患者10年总体生存率为70.27%,其中,无功能性腺瘤与功能性腺瘤的10年生存率分别为66.72%与75.31%。［结论］ 垂体瘤多发于41~70岁人群,以大腺瘤最为多见,MRI对微腺瘤的检出率高于CT。患者术后生存情况相对较好,其中功能性腺瘤患者的生存情况优于无功能性腺瘤患者,应加大对无功能腺瘤患者的临床关注。     

Ki-67和cyclin D1蛋白表达的检测对胃肠道间质瘤良恶性判断的意义

目的　探讨Ki -67和cyclinD 1蛋白表达的检测对胃肠道间质瘤(GISTs)良恶性判断的意义。方法　应用免疫组织化学EnVision二步法检测41例GISTs组织中Ki -67和cyclinD1蛋白表达情况。结果　41例GISTs分为良性组(6例)、交界组(13例)和恶性组(2 2例) ,良性组、交界组与恶性组GISTs的Ki- 67标记指数分别为(8.5±3 .9) %、(16.8±8.6) %和(2 1.8%±8.3 ) % ,3组Ki 67标记指数比较有非常显著性差异(P <0 .0 1) ;Ki- 67标记指数与核分裂像数目、肿瘤直径及肿瘤坏死有关。良性组、交界组与恶性组GISTs的cyclinD1阳性表达率分别为16.7% (1/6)、5 3 .8% (7/13 )和68.2 % (15 /2 2 ) ,3个组cyclinD 1阳性表达率比较有显著性差异(P <0 .0 5 ) ,且良性组与交界组以及良性组与恶性组间cyclinD1阳性表达率有显著性差异(P <0 .0 5 ) ,但交界组和恶性组cyclinD1阳性表达率比较无显著性差异(P >0 .0 5 ) ;cyclinD 1阳性表达率与核分裂象数目有关,而与肿瘤直径及肿瘤坏死无关。结论　Ki- 67和cyclinD1蛋白是胃肠道间质瘤良恶性判断的有价值参考指标,结合胃肠道间质瘤形态学综合分析,更能准确客观地判断胃肠道间质瘤的良恶性。     

食管鳞癌中CDK4表达及意义的研究

目的　研究CDK4在食管鳞癌中的表达、发生过程中的影响以及在其增殖、侵袭、转移中的作用。方法　运用免疫组织化学方法 (SABC法 )研究CDK4蛋白表达情况 ,显微镜下计数阳性细胞指数 (LI) ,并进行统计分析。结果　 1)CDK4表达情况 :正常食管黏膜组织阳性率与食管鳞癌组织比较差异有显著性 ,后者高于前者 ( χ2 =5 .42 99,P =0 .0 2 0 ) ,LI后者高于前者 (t =2 .42 3 ,P =0 .0 19) ,1例正常食管黏膜阳性者为弱阳性 (LI <2 5 %)。 2 )CDK4在食管鳞癌组织中的表达与年龄、性别无明显关系 (P >0 .0 5 ) ,不同分化级别中两者表达亦无差异 (P >0 .0 5 )。有淋巴结转移组CKD4水平分别高于无淋巴结转移组 ,差异有显著性 (P =0 .0 0 1)。食管外膜浸润组CDK4显著高于未受浸润组 ,(P =0 .0 0 0 ) ,临床分期Ⅰ～Ⅱ与Ⅲ～Ⅳ期CDK4表达水平差异有显著性 ,(P =0 .0 0 0 )。结论　CDK4在食管鳞癌中高表达 ,促进了细胞生长和肿瘤发展 (G1 →S过渡 ) ,反应了肿瘤的生物学特性 ,促进侵袭转移 ,是食管癌发生发展中的重要事件。     

EGFR、p53、Bcl-2表达,Ki-67标记指数与胸腺瘤WHO组织学分型、分期及预后的关系

目的探讨EGFR、p53、Bcl-2表达，Ki-67标记指数（Ki-67Li）与胸腺瘤WHO组织学分型、分期及预后的关系。方法应用免疫组化染色方法检测46例胸腺瘤患者EGFR、p53、Bcl-2的表达和Ki-67标记指数。结果胸腺瘤EGFR、p53、Bcl-2阳性表达率分别为34．8％、56．5％、54．3％，Ki-67标记指数平均值为11．0％。EGFR、p53、Bcl-2蛋白表达与胸腺瘤WH0组织学分型均无明显关系；B2、B3、C型与A、AB、B1型之间Ki-67标记指数表达差异有显著性（P〈0．05）；Bcl-2蛋白表达与胸腺瘤Masaoka分期和预后均无关系（P〉0．05）；EGFR、p53蛋白的过度表达和Ki-67标记指数与胸腺瘤Masaoka分期明显相关（P〈0．05）；Ki-67标记指数与预后有关（P〈0．05）。结论EGFR、p53蛋白的过度表达和Ki-67标记指数与胸腺瘤Masaoka分期明显相关，反应其侵袭性，Ki-67标记指数还与组织学分型相关，并可作为估计胸腺瘤预后的参考指标。     

人垂体腺瘤组织p16基因表达临床意义的研究

目的：探讨垂体腺瘤组织中p16基因表达与临床病理特征及肿瘤侵袭性之间的关系。方法：应用免疫组化SP法和RT-PCR检测48例垂体腺瘤组织p16的表达情况。结果：48例肿瘤标本中有11例（22．9％）存在p16蛋白表达，侵袭性腺瘤表达缺失明显高于非侵袭性腺瘤，P〈0．01；p16阴性表达腺瘤直径明显大于阳性表达腺瘤，P〈0．01；p16蛋白表达与患者年龄、性别及垂体腺瘤分泌功能无关。结论：p16基因表达缺失与腺瘤大小有关，p16基因缺失通常是在垂体腺瘤生长过程中逐渐出现的晚期事件。     

MCM2、Ki67、CyclinD1在甲状腺滤泡性癌和滤泡性腺瘤组织中的表达及与Galectin-3、CK19的对比研究

目的 探讨MCM2、Ki67、CyclinD1在甲状腺滤泡性癌和甲状腺滤泡性腺瘤组织中表达的意义,并与Galectin-3、CK19进行对比.方法 应用免疫组织化学EnVision法检测32例甲状腺滤泡性癌及23例甲状腺滤泡性腺瘤组织中MCM2、Ki67、CyclinD1、Galectin-3和CK19的表达情况.结果 MCM2、Ki67、CyclinD1的阳性率在甲状腺滤泡性癌组织中分别为96.9%、46.9%、96.9%,在甲状腺滤泡性腺瘤中分别为65.2%、26.1%、100.0%,两者MCM2的阳性率比较差异有统计学意义（χ2=9.799,P=0.002）,而两者Ki67和CyclinD1的阳性率比较差异无统计学意义（χ2=2.450、0.732,P=0.118、0.392）.在滤泡性癌和滤泡性腺瘤组织中,MCM2、ki67、CyclinD1者的标志指数分别为（31.51±19.43）和（11.12±10.79）、（6.58±6.40）和（4.03±5.14）、（50.00±21.70）和（40.33±22.55）,MCM2的标志指数比较差异有统计学意义（t=10.522,P〈0.001）,Ki67和CyclinD1的标志指数比较差异无统计学意义（t=1.589、1.634,P=0.122、0.115）.Galectin-3和CK19的阳性率在滤泡性癌组织中分别为62.5%和75.0%,在滤泡性腺瘤组织中分别为26.1%和60.9%,Galectin-3的阳性率比较差异有统计学意义（χ2=7.118,P=0.008）,CK19的阳性率比较差异无统计学意义（χ2=1.251,P=0.263）.结论 MCM2、Galectin-3在甲状腺滤泡性癌与滤泡性腺瘤组织中的表达有明显差异,对两者的诊断和鉴别诊断有价值,而Ki67、CyclinD1、CK19则无价值.     

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。     

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(英文)

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。     

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.     

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。     

Ki-67在垂体瘤、脑膜瘤、脑血管母细胞瘤中的表达及其临床意义

背景与目的：垂体瘤、脑膜瘤和脑血管母细胞瘤作为颅内常见良性肿瘤，术后常有复发，本研究探讨Ki-67在三者中的表达及其与复发的关系。方法：采用免疫组化SP法．检测Ki-67在56例垂体瘤、60例脑膜瘤和43例脑血管母细胞瘤中的表达．以显微镜下细胞核出现棕黄色颗粒计算Ki-67标记指数，并进行统计学分析。结果：Ki-67表达在垂体瘤侵袭性组高于非侵袭性组，脑膜瘤与脑血管母细胞瘤的复发组高于非复发组，差异均有统计学意义（P〈0．05）。结论：检测垂体瘤、脑膜瘤和脑血管母细胞瘤中Ki-67表达对评估肿瘤术后复发有一定参考价值。     

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.     

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。     

Study on Ki-67 immunoreactivity as a prognostic indicator in patients with advanced gastric cancer

BACKGROUND: Cell proliferation characteristics may reflect the aggressiveness of gastric tumors and their eventual prognosis. The aim of this study was to evaluate whether the proliferative activities determined by the antibody Ki-67 could be used as a prognostic predictor in patients affected by advanced gastric cancer. METHODS: The prognostic significance of proliferative activity was investigated in 56 patients who underwent curative gastrectomy (R0) for advanced gastric cancer using the monoclonal antibody Ki-67. The patients were divided into three groups according to the Ki-67 labeling index of the tumors: < 10% (18 cases), 10-40% (21 cases) and > 40% (17 cases). The Cox regression model was used to evaluate the prognostic significance of the Ki-67 index controlling for age, gender, histology, depth of tumor invasion and node metastasis. RESULTS: There was no significant relationship between the Ki-67 index and wall invasion (P = 0.80) or nodal status (P = 0.73). The cumulative 3-year survival rates (95% Cl) were 61.0% (35.3-79.2%) in patients with Ki-67 index < 10%, 52.4% (29.7-70.9%) with Ki-67 index 10-40% and 52.9% (27.6-73.0%) with Ki-67 index > 40% and the differences were not statistically significant (P = 0.93). Also in multivariate analysis the proliferative activity did not independently affect survival (P = 0.98). An interaction between Ki-67 index and age was found and Ki-67 index > 40% was significantly associated with a poor prognosis in patients over 68 years old (P = 0.004). CONCLUSION: Our study indicated that the proliferative activity in gastric cancer, determined with the monoclonal antibody Ki-67, does not influence the survival except in elderly patients (> or = 68 years old).      

Lack of correlation between Ki-67 labelling index and tumor size of anterior pituitary adenomas

Aims and background  

The Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its Labeling Index (LI) is considered a marker of normal and abnormal cell proliferation. Pituitary adenomas are generally well differentiated neoplasms, even if in about one third of cases they are invasive of surrounding tissues. The aim of this study is to evaluate the correlation between Ki-67 labelling index and tumor size of pituitary adenomas extimated by means CT and MRI and confirmed at operation.     

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.