微血管密度和Ki—67指数与星形胶质瘤临床病理关系的研究

目的寻求判断星形胶质瘤恶性程度和预后的量化指标.方法采用免疫组化染色技术对48例星形胶质瘤组织微血管密度(MVD)和Ki-67指数(Ki-67LI)进行测定.结果低度恶性肿瘤中MVD和Ki-67LI分别为8.89±5.80和6.69±4.81,在高度恶性肿瘤中分别为17.49±13.13和23.62±6.78,具有显著性差异;术后生存2年以上者,其2个指标值均低于术后生存不足2年者.但MVD和Ki-67LI在不同性别、年龄间的比较,无显著性差异.结论MVD和Ki-67LI均可作为判断星形胶质瘤恶性程度和预后的指标;同时检测两者可互为补充.     

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。     

肝细胞癌p53和VEGF的表达及其与肿瘤血管形成的关系

目的 :研究p5 3和血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的表达和肿瘤微血管密度 (microvesseldensity ,MVD)测定在人肝细胞癌 (HCC)中的意义。方法 :采用免疫组织化学方法 ,检测 5 0例HCC患者手术切除标本p5 3和VEGF的表达 ,并用抗CD3 4 抗体标记癌组织血管内皮细胞 ,计算MVD。结果 :p5 3、VEGF总阳性表达率分别为 5 4 0 % (2 7 5 0 )和 76 0 % (38 5 0 ) ,p5 3、VEGF的表达和MVD均与HCC组织病理分级呈正相关 ,P <0 0 5。p5 3和VEGF的阳性表达符合率为 74 % (37 5 0 ) ,两者的表达呈相关性 ,P <0 0 5。p5 3阳性和VEGF阳性的癌组织MVD分别为 178± 6 2和 175±5 9 ,而相应的阴性组分别为 12 5± 5 1和 131± 6 1,两者差异有显著意义 ,P <0 0 5。p5 3、VEGF表达均为阳性者 ,MVD为 176± 6 3;p5 3、VEGF的表达均为阴性者 ,MVD为 12 3± 5 2 ;两者差异有显著意义 ,P <0 0 5。结论 :1)p5 3、VEGF的表达以及MVD的测定可作为判断HCC恶性潜能的重要生物学指标 ;2 )p5 3、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测p5 3、VEGF的表达对了解肿瘤血管形成的机制有一定意义     

EphB4/EphrinB2在人脑星形细胞瘤中的表达及其病理学意义

目的：探讨EphrinB2与其受体EphB4、微血管密度（mierovessel density，MVD）和Ki-67在人脑星形细胞瘤中的表达及其病理学意义。方法：采用组织芯片技术和Maxvision^TM快捷免疫组织化学染色方法检测84例人脑星形细胞瘤和12例外伤脑组织中EphB4／EphrinB2、MVD和Ki-67的表达。结果：EphB4／EphrinB2、MVD、和Ki-67标记指数（Ki-67 labelling index．Ki-67LI）在人脑星形细胞瘤组和对照组之间的差异有统计学意义（P〈0．05）。EphB4、EphrinB2、MVD和Ki-67 LI与肿瘤级别呈正相关，MVD和Ki-67 LI与EphB4或EphrinB2蛋白表达正相关，有统计学意义（P〈0．05）。结论：EphB4和EphrinB2与人脑星形细胞瘤的分化程度和肿瘤血管生成密切相关，EphB4和EphrinB2的过度表达对肿瘤发展和促进肿瘤血管的生成起重要作用。利用EphB4／EphrinB2、MVD和Ki-67来判断人脑星形细胞瘤的恶性程度和病理特征，是一个较好的参考指标。     

缺氧诱导因子-1α,VEGF和MVD在直肠癌中的表达及临床意义

目的　探讨直肠癌中 HIF- 1α、VEGF和 MVD表达的相互关系及临床意义。方法　应用免疫组化 S- P法检测 88例直肠癌组织中 HIF- 1α、VEGF的表达 ,用 CD34单克隆抗体标记肿瘤微血管密度 (MVD)。结果　直肠癌组中 HIF- 1α、VEGF的阳性表达率分别为 6 5 .9% (5 8/ 88)和 6 3.6 % (5 6 / 88)明显高于正常对照组的 16 .7% (2 /12 )和 0 % (P<0 .0 1) ;直肠癌组中 MVD平均为 2 9.6± 6 .1,正常对照组为 14 .0± 5 .8(P<0 .0 1)。HIF- 1α、VEGF与MVD的表达呈显著正相关 (P<0 .0 1)。 HIF- 1α、VEGF和 MVD的表达与肿瘤 Dukes分期、淋巴结转移、远处转移显著相关 (P<0 .0 5 )。而与肿瘤的病理类型、分化程度无明显相关性。在 HIF- 1α、VEGF表达阳性组和阴性组的 5年生存率分别为 4 1.4 % vs80 .0 % ;37.93% vs86 .7% (P<0 .0 1)。结论　 HIF- 1α的过度表达与直肠癌的肿瘤血管新生显著相关。 HIF- 1α、VEGF可作为判断直肠癌预后的参考指标     

食管癌原发灶及转移淋巴结血管内皮生长因子和微血管形成的测定

目的 :探讨食管鳞状细胞癌原发灶和淋巴结转移灶血管内皮生长因子 (VEGF)表达及微血管形成的规律。方法 :用免疫组化方法测定 35例食管癌标本原发灶和转移灶VEGF表达水平及微血管密度(MVD)。结果 :淋巴结转移灶VEGF表达水平高于原发灶 (P <0 .0 1) ;淋巴结转移灶、原发灶及阴性淋巴结MVD分别为 11 33± 4 .4 4、13 85± 5 57、18 6 1± 6 6 7,淋巴结转移灶与后两者相比差异均有显著性 (P <0 .0 1)。结论 :转移灶VEGF表达水平高于原发灶 ,淋巴结内可能存在抗肿瘤血管生成因素。     

Ki-67抗原对幕上高级别星形细胞肿瘤的预后作用

目的 :探讨 Ki- 6 7抗原在幕上高级别星形细胞肿瘤中的表达及其预后作用。方法 :使用 S- P免疫组化方法检测 6 3例原发性幕上高级别星形细胞肿瘤标本中 Ki- 6 7抗原的表达。单因素分析使用 Kaplan- Meier法 ,多因素分析使用 COX比例风险模型进行预后分析。结果 :Ki- 6 7指数在组织学分级 级、 级中分别为 (7.32± 3.2 4) %、(7.48± 4.5 5 ) % (P>0 .0 5 )。Ki- 6 7指数≤ 2 .5 %与 >2 .5 %的患者生存期分别为 (4 2 .42± 13.46 )月、(19.95± 11.0 7)月 (P<0 .0 1)。单因素及多因素分析均显示 Ki- 6 7指数是独立的预后因素。结论 :在幕上高级别星形细胞肿瘤中 ,组织病理分级本身对患者预后无意义 ;Ki- 6 7指数与病理级别无关 ;Ki- 6 7指数 >2 .5 %提示预后较差 ;Ki- 6 7指数是患者独立的预后因素     

HIF-1 α、VEGF及Ki-67在脑星形胶质瘤的表达

[目的]研究HIF-1α、VEGF及Ki-67在星形胶质瘤中表达情况以及它们与某些临床因素的关系。[方法]应用免疫组化法检测71例星形胶质瘤中HIF-1α、VEGF及Ki-67蛋白表达情况。[结果]HIF-1α、VEGF在星形胶质瘤中的阳性表达率分别57.7%和64.8%,在不同恶性级别组中差异均具有显著性,与肿瘤的恶性程度相关。Ki-67在胶质瘤中的阳性表达率为100%,Ki-67LI为0.4%～89%。HIF-1α和VEGF、Ki-67正相关。Ki-67与VEGF呈正相关性。[结论]HIF-1α通过对VEGF、Ki-67作用促进胶质瘤血管生成和肿瘤细胞增殖,三者在肿瘤的恶性进展过程中起作用。     

血管内皮生长因子在脑星形细胞瘤中的表达及其意义

目的　探讨血管内皮生长因子 (VEGF)在脑星形细胞瘤中的表达及其与肿瘤生长、预后和血管生成的关系。方法　应用免疫组化方法检测 82例脑星形细胞瘤瘤组织中VEGF表达、MVD ,并分析VEGF表达与血管生成、病理分级、临床预后等临床病理的关系。结果　VEGF表达与MVD呈正相关 (r=0 .6 3,P <0 .0 1)。星形细胞瘤病理级别越高 ,VEGF表达越强 (P <0 .0 5 ,0 .0 1)。瘤周水肿越重 ,VEGF表达也越强 (P <0 .0 5 ,0 .0 1)。VEGF表达与星形细胞瘤的大小、发生部位及男女性别无明显的相关关系 (P >0 .0 5 )。结论　星形细胞瘤的VEGF表达与其血管生成、预后及病理分级密切相关 ,可作为判断预后的独立指标。     

环氧合酶-2对胃癌血管内皮生长因子及血管形成的影响

 目的　探讨环氧合酶 2 (COX 2 )对胃癌血管内皮生长因子 (VEGF)的表达及血管生成的影响。方法　应用免疫组织化学技术检测胃癌组织中COX 2 ,VEGF表达和微血管密度 (MVD)。结果　COX 2在62 .2 %胃癌组织中表达增高 ,COX 2表达与VEGF表达显著相关 (γS=0 .5 85 ,P <0 .0 1 ) ,且COX 2和VEGF均阳性的胃癌组织MVD(64.0± 2 5 .4)亦明显高于两者均阴性者 (3 0 .7± 1 1 .5 ) (P <0 .0 1 )。结论　胃癌组织中存在COX 2的高表达 ,COX 2通过增加VEGF表达而促进肿瘤血管形成     

Ki-67、VEGF在胃肠间质瘤中表达及与MVD的相关性

目的:探讨Ki-67和VEGF在胃肠间质瘤中的表达及与临床病理因素的关系,VEGF、微血管密度(MVD)和细胞增殖之间的相关性。方法:采用免疫组化S-P法检测44例胃肠间质瘤组织中Ki-67、VEGF表达及计数MVD值和Ki-67PI。结果:VEGF、Ki-67在GIST组织中阳性表达分别为77.3%、63.6%,VEGF、Ki-67表达在不同大小的肿块之间有统计学差异(P<0.01);MVD值和Ki-67PI在VEGF阳性和阴性组的比较有统计学差异(P<0.01);VEGF、MVD和Ki-67PI之间呈显著正相关(相关系数分别为0.26、0.44和0.84,P<0.01)。结论:VEGF促进GIST组织中的新生血管形成,为肿瘤组织提供了丰富的血液和营养,并使细胞增殖活性增强,促进肿瘤细胞的增殖、肿瘤的生长、发展和转移;Ki-67PI为GIST的预后判断提供了比较客观的依据。     

Prognostic Value of the Expression of Tumor Suppressor Genes p53, p21, p16 and pRb, and Ki-67 Labelling in High Grade Astrocytomas Treated with Radiotherapy

Cumulative inactivation of tumor suppressor genes and/or amplification of oncogenes lead to progressively more malignant astrocytic tumors. We have analyzed the significance of tumor suppressor genes p53, p21, p16 and retinoblastoma protein (pRb) and proliferative activity for survival in 77 high grade astrocytic tumors.After operation, the patients – 25 anaplastic astrocytomas (AA) and 52 glioblastomas (GBs) – were treated with similar radiotherapy. The expression of the suppressor genes and the proliferative activity were analyzed immunohistochemically.p53 immunopositivity was found in 44% of AAs and 46% of GBs. Tumors with aberrant p53 expression had lower proliferation indices than p53 immunonegative tumors. Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16 immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated inversely with survival in both uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusive.Ki-67 labelling index (LI) was significantly higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20% and this subset of AAs had similar prognosis as GB.In high grade astrocytic tumors p16 immunonegativity was an independent indicator of poor prognosis in addition to the previously established patient's age, histopathology and Ki-67 LI. Furthermore, there was a subset of AAs with a high proliferation rate (>20%) in which the histopathological hallmarks of GB were lacking, but which had similarly dismal prognosis as GB.     

Predictive value of Smac, VEGF and Ki-67 in rectal cancer treated with neoadjuvant therapy

The present study aimed to identify whether second mitochondria-derived activator of caspase (Smac), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki-67) expression in pre-treatment tumor biopsies are useful predictive markers of tumor response in patients with rectal cancer undergoing pre-operative chemoradiotherapy (CRT). Paraffin-embedded tissues obtained before and after therapy were evaluated by immunohistochemical staining for Smac, VEGF and Ki-67. The study evaluated the correlation of Smac, VEGF and Ki-67 immunoreactivity in tumor biopsies before treatment of tumor response to pre-operative CRT. Regarding Smac, patients with a favorable response to neoadjuvant CRT had higher pre-therapy levels (p=0.011). The level of Smac expression decreased after neoadjuvant therapy (p=0.044). However, VEGF expression was found to be negatively and significantly correlated with a favorable tumor response to neoadjuvant CRT (p=0.010). A transient increase in VEGF expression was detected in the resected specimens following neoadjuvant therapy (p=0.030). In addition, tumors with a low Ki-67 labeling index (Ki-67-LI) expression were found to be more sensitive to neoadjuvant therapy than those with a high expression of Ki-67-LI (p=0.034). In contrast to VEGF, the Ki-67 expression level decreased after neoadjuvant therapy. Smac, VEGF and Ki-67 expression levels, assessed immunohistochemically from pre-treatment tumor biopsies, may be useful predictive markers of rectal tumor response to pre-operative CRT.     

脑星形细胞肿瘤中FAK、Pyk2表达及其与血管生成的关系

Objective: To study the expressions of FAK and Pyk2 in human astrocytic tumors and their relationship with an-giogenesis. Methods: The S-P immunohistochemical method was used to measure the expressions of FAK, Pyk2 and VEGF proteins in 58 human brain astrocytic tumors, and microvessel density (MVD) was detected by CD31 staining. Results: In astrocytic tumors with I, II, III and IV grades, the positive rates of FAK were 20.00%, 26.67%, 44.44% and 50.00%, respec-tively, those of Pyk2 were 40.00%, 60.00%, 77.78% and 85.00%, respectively. FAK and Pyk2 expressions, especially Pyk2, correlated positively with VEGF expression and MVD. Conclusion: FAK and Pyk2 plays the important role in astrocytic tumor angiogenesis through regulation to VEGF.     

1 267例乳腺癌临床与免疫组化指标的相关性分析

分析乳腺浸润性导管癌的临床特征及6种免疫组化指标表达的关系,探讨其临床意义。方法:采用免疫组化SP法对1 267例乳腺癌患者的术后肿瘤石蜡标本进行ER、PR、C-erbB-2、P53、Ki-67、VEGF检测,并与患者的临床特征进行相关分析。结果:乳腺癌组织中ER、PR、C-erbB-2的阳性表达率分别为61.4%、53.0%、36.6%;P53、Ki-67、VEGF的阳性表达率分别为42.0%、91.6%、74.7%。肿瘤直径≤2 cm组中,ER和PR表达率最高（66.8%和58.8%）,而C-erbB-2的表达率最低（32.9%）。在低年龄组（≤50岁）和临床I期的患者中,PR表达率均最高,为57.9%和58.5%。C-erbB-2在临床晚期（Ⅲ,Ⅳ期）表达率最高（45.9%）。P53、Ki-67的阳性表达均与ER阳性表达呈负相关。而P53、Ki-67、VEGF的阳性表达与C-erbB-2的表达均呈正相关。淋巴结阳性组中P53、Ki-67与ER及P53与C-erbB-2的相关程度均较淋巴结阴性组大。结论:乳腺浸润性导管癌组织中ER、PR、C-erbB-2与P53、Ki-67和VEGF之间有一定的相关性,联合检测有助于指导该类肿瘤的治疗。      

脑星形细胞肿瘤中FAK、Pyk2表达及其与血管生成的关系

背景与目的：非受体酪氨酸蛋白激酶家族成员FAK和Pyk2具有高度同源性,对肿瘤细胞增殖和侵袭具有重要的调控作用,但其是否参与肿瘤血管生成过程尚不明确。本研究旨在探讨FAK和Pyk2在脑星形细胞肿瘤中表达与血管生成的关系。方法：应用免疫组化法检测58例脑星形细胞肿瘤中FAK、Pyk2和血管内皮生长因子（VEGF）表达,并用CD31标记计数瘤内微血管密度。结果：FAK、Pyk2蛋白主要表达于肿瘤细胞胞浆,Pyk2阳性表达也见于肿瘤血管内皮细胞。在Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞肿瘤中,FAK阳性率分别为20.0%（1/5）、26.7%（4/15）、44.4%（8/18）、50.0%（10/20）,Pyk2阳性率分别为40.0%（2/5）、60.0%（9/15）、77.8%（14/18）、85.0%（17/20）;FAK和Pyk2阳性表达强度评分在Ⅱ级星形细胞肿瘤与Ⅲ、Ⅳ级星形细胞肿瘤中具有显著差异性（P〈0.05）。FAK、Pyk2表达与VEGF和微血管密度呈正相关,相关系数分别为rs=0.423（P=0.001）和rs=0.729（P〈0.005）。结论：FAK、Pyk2可能通过与VEGF的相互作用而参与脑星形细胞肿瘤的血管生成过程。     

Expression of vascular endothelial growth factor and angiogenesis in gastrointestinal stromal tumor of the stomach

Vascular endothelial growth factor (VEGF) is associated with the malignant potential of several types of carcinoma. The aim of this study was to elucidate the clinical significance of VEGF expression in gastrointestinal stromal tumor (GIST). METHODS: Specimens obtained from 53 patients who had underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for VEGF expression and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody, and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. RESULTS: VEGF expression was detected in 14 (26.4%) of the 53 lesions and correlated significantly with tumor size, liver metastasis, Ki-67 labeling index, and MVD. Prognosis was significantly poorer than in patients with tumors expressing VEGF than in patients with tumors lacking VEGF expression. Multiple logistic regression analysis for 10-year survival showed VEGF expression and high mitotic rate to be independent predictor of a poor outcome. CONCLUSIONS: Angiogenesis associated with VEGF may play an important role in the progression of GIST. VEGF expression may serve as an indicator of a poor prognosis.     

Expression of Ki-67, p53 and VEGF in Pediatric Neuroblastoma

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is thesecond most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous.This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained fromNB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blockswere constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMAsections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression ofthese markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB,one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%)tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High andmoderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it waspositively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI(mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relativecorrelation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapywas correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as avaluable marker for the prognosis of this tumor type.