分化抑制因子Id-1与VEGF及MVD在宫颈癌变中的相关性分析

目的:研究分化抑制因子-1(Id-1)与血管内皮生长因子(VEGF)及微血管密度(MVD)在宫颈组织癌变中的相关性,探讨Id-1在宫颈癌血管形成中的机理。方法:采用免疫组化法检测50例宫颈癌石蜡标本中Id-1、VEGF及CD34的表达;用CD34标记肿瘤微血管,计算MVD。结果:宫颈癌组织中Id-1、VEGF及MVD均呈高表达,且均与临床FIGO分期进展具有相关性(P<0.05)。宫颈癌组织中三者的表达具有显著正相关性(P<0.01),Id-1与VEGF、Id-1与MVD的spearman相关系数(Ra)分别为0.43,0.48。结论:宫颈癌组织中Id-1与VEGF、MVD的表达具有正相关性,Id-1可能是通过促进肿瘤微血管生成的机制参与宫颈癌的发生。     

Angiogenesis in malignancies of the female genital tract

OBJECTIVE: The purpose of this work was to review current knowledge pertaining to angiogenesis in malignancies of the female genital tract. METHODS: We identified studies published in the English language regarding angiogenesis in gynecologic malignancies. The studies were obtained from a MEDLINE search from 1966 through June 1998; additional sources were identified through cross-referencing. RESULTS: A growing body of evidence confirms the ability of vulvar and cervical squamous cell carcinomas and endometrial and ovarian adenocarcinoma to induce angiogenesis. In vulvar intraepithelial neoplasia a correlation between vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), and progression of dysplasia has been demonstrated. In invasive vulvar carcinoma, high VEGF expression and MVD portend poor prognosis. Currently a debate exists regarding the ability of cervical squamous intraepithelial neoplasia to induce angiogenesis. Most studies, however, indicate angiogenesis to be of prognostic value in patients with invasive squamous cell carcinoma. The ability of complex endometrial hyperplasia to induce angiogenesis has been demonstrated. A direct correlation between angiogenesis, higher grade and depth of invasion in Stage I adenocarcinoma, and prognostic value in Stage I and II and recurrent disease has been noted. In ovarian epithelial adenocarcinoma, higher microvessel counts in the primary ovarian tumor or omental metastases may serve as a prognostic indicator for survival. CONCLUSIONS: Similar to other malignant diseases, angiogenesis appears to play an important role in disease progression and survival in patients with gynecologic malignancies. Preliminary data indicate angiogenesis may serve as a prognostic indicator in vulvar and cervical squamous cell carcinomas and endometrial and ovarian adenocarcinomas. These findings may lead to future application of therapeutic trials with antiangiogenic factors.     

缺氧相关因子HIF-1α、AQP-1表达与宫颈鳞状细胞癌血管生成关系的研究

目的:探讨HIF-1α、AQP-1表达对宫颈鳞状细胞癌血管生成的作用。方法:应用免疫组织化学方法检测54例宫颈鳞状细胞癌中HIF-1α、AQP-1的表达,用CD105标记肿瘤微血管密度。结果:HIF-1α在宫颈鳞状细胞癌的阳性表达率为50%,表达水平与分化程度、浸润深度明显相关(r=-0.674,P0.05和r=0.897,P0.01),与临床分期、肿瘤体积、淋巴结转移无明显相关(P0.05)。AQP-1在宫颈鳞状细胞癌的表达率为87.1%,表达水平与肿瘤体积、临床分期明显相关(r=0.989,P0.05和r=0.807,P0.01),与分化程度、淋巴结转移、浸润深度无明显相关(P0.05)。微血管密度与肿瘤体积、浸润深度明显相关(r=0.609,P0.05和r=0.845,P0.01);与临床分期、分化程度、淋巴结转移无明显相关(P0.05)。微血管密度与HIF-1α表达明显相关(r=0.701,P0.05),而与AQP-1的表达无关(P0.05)。AQP-1的表达水平与HIF-1α的表达水平明显相关(r=0.648,P0.05)。结论:HIF-1α、AQP-1均参与宫颈鳞状细胞癌缺氧诱导新生血管过程,并且与微血管密度密切相关,其中HIF-1α发挥重要作用。     

血管内皮生长因子和微血管密度在宫颈癌中表达的研究

目的探讨血管内皮生长因子(VEGF)和微血管密度(MVD)在宫颈癌血管生成中的作用及其与临床病理因素的关系。方法 应用免疫组化ABC法检测62例宫颈癌和18例正常宫颈组织血管内皮生长因子及Ⅷ因子的蛋白表达。结果 VEGF在宫颈癌中的阳性表达率为56.5％,正常宫颈组织中无VEGF阳性表达。肿瘤内MVD为(25.0±8.5)个/高倍视野,明显高于正常宫颈组织(13.6±5.7)个,高倍视野,VEGF表达阳性肿瘤的MVD明显高于阴性者(P<0.05)。腺癌组织中MVD和VEGF水平明显高于鳞癌组织(P<0.005和P<0.05)。结论 VFGF能促进宫颈癌新生血管形成,可能对腺癌的作用更重要。     

VEGF、P53在卵巢上皮性肿瘤的表达及其与血管生成关系的研究

目的探讨VEGF、P53在卵巢上皮性肿瘤中的表达及其与血管生成的关系,旨在了解卵巢上皮性肿瘤血管生成活性及其调节机制,为卵巢癌的治疗提出新的思路.方法采用免疫组化LSAB法分析74例卵巢上皮性肿瘤微血管密度(MVD)、血管内皮生长因子(VEGF)和P53蛋白的表达状况及三者间的关系.结果MVD在腺瘤、交界瘤、卵巢癌中的数值依次升高,各组间差异均有显著性(P＜0.001,P＜0.05);MVD在卵巢癌中粘液性明显高于浆液性和子宫内膜样(P＜0.05,P＜0.05);VEGF在卵巢癌中的表达率明显高于腺瘤及交界瘤(P＜0.05).P53蛋白仅出现于卵巢癌组织,表达率50%,卵巢癌P53蛋白阳性组MVD高于P53阴性组(P＜0.05);等级相关分析显示卵巢上皮性肿瘤VEGF的表达强度与MVD呈正相关(r=0.762,P＜0.001);P53、VEGF间也存在正相关关系(ra=0.762,P＜0.01).结论血管生成活性的不同,有助于卵巢良、恶性肿瘤的鉴别;VEGF是卵巢上皮性肿瘤重要的促血管生成因子,且可能与卵巢癌腹水形成有关;P53突变可促进卵巢上皮性癌的血管生成,且在一定程度上可上调VEGF表达.     

Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression

OBJECTIVE: The purpose of this study was to evaluate vascular endothelial growth factor (VEGF) expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and expression of p53 and c-erbB-2 proteins. METHODS: Thirty-seven cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-VEGF, anti-CD34, anti-p53, and anti-c-erbB-2 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD). RESULTS: Thirty-one tumors (83.8%) were classified as VEGF positive. Six tumors (16.2%) showed p53 protein expression while 11 tumors (29.7%) expressed the c-erbB-2 protein. MVD ranged from 13.3 to 44.8, with a median value of 25.5 (26.9 +/- 7.5). Tumors expressing VEGF had a significantly higher MVD than those that did not express VEGF (P < 0.05). VEGF expression was significantly associated with c-erbB-2 protein expression (P < 0.05). The spatial distributions of both VEGF expression and c-erbB-2 expression were similar in tumor tissues. In univariate log-rank analysis, stage (P = 0.0250), lymphovascular space invasion (P = 0.0156), and MVD (P = 0.0360) were associated with shortened survival. CONCLUSION: VEGF expression plays a role in promoting angiogenesis in cervical adenocarcinomas and c-erbB-2 is likely to be involved in the up-regulation of VEGF expression.     

分化抑制因子-1在宫颈癌组织中表达及其与微血管密度的关系

目的探讨分化抑制因子-1(Id-1)在宫颈癌组织中的表达及其与肿瘤发生、发展以及血管生成的关系。方法 2009年2月至2010年6月在吉林大学第二临床医院采用免疫组化法检测35例宫颈浸润癌(ICC)组织及20例正常宫颈上皮组织(NCE)中Id-1和微血管密度(MVD)的表达。结果 Id-1蛋白在宫颈癌组织中阳性表达率为71.43%,正常宫颈上皮组织中阳性表达率为0,两组比较有统计学意义(P<0.01),ICC组Id-1高表达与组织分化程度、间质浸润深度和盆腔淋巴结转移相关(P﹤0.05),而与FIGO分期无关(P﹥0.05);MVD计数在宫颈癌组织中表达为46.57±10.291,在正常宫颈上皮组织中为12.40±3.761,两组比较有统计学意义(P<0.05),MVD的表达在ICC组内与盆腔淋巴结转移、组织分化程度有关(P﹤0.05),而与FIGO分期、间质浸润深度无关(P﹥0.05);ICC组中Id-1表达强度与MVD呈正相关(r=0.648,P﹤0.01)。结论 Id-1因子通过促进肿瘤血管生成,从而参与宫颈癌的发生发展;子宫颈癌组织中的MVD值随着Id-1因子表达强度的增加而增高。阻断Id-1因子在子宫颈癌中的表达,有望成为治疗宫颈癌的途径之一。     

放置宫内节育器对子宫内膜血管内皮生长因子及其激酶受体表达及微血管密度变化的影响

目的探讨放置固定式带铜宫内节育器(FCu-IUD)和含吲哚美辛FCu-IUD(FICu-IUD),对子宫内膜组织中血管内皮生长因子(VEGF)及其激酶受体(KDR)表达以及微血管密度(MVD)变化的影响及意义.方法采用免疫组化法及原位杂交法,检测放置FCu-IUD妇女(10例,FCu-IUD组)及放置FICu-IUD妇女(10例,FICu-IUD组)放置IUD前后子宫内膜VEGF、VEGF mRNA及KDR的表达,并计数子宫内膜MVD.结果 FCu-IUD组放置IUD后,VEGF及KDR蛋白为0.568±0.027,0.244±0.022,均高于放置IUD前的0.357±0.032,0.215±0.029,放置IUD前后比较,差异有显著性(P<0.05).FCu-IUD组放置IUD前VEGF mRNA表达为0.359±0.022,低于放置IUD后的0.425±0.019,放置IUD前后比较,差异有显著性(P<0.05).FICu-IUD组放置IUD前后VEGF、KDR蛋白及VEGF mRNA表达比较,差异无显著性(P>0.05). FCu-IUD组放置IUD后MVD为19.8±4.8,明显高于放置IUD前的15.4±2.8,且与VEGF蛋白的表达呈正相关关系(r=0.847,P<0.01).FICu-IUD组放置IUD前后MVD比较,差异无明显性(P>0.05).结论放置FCu-IUD可促进子宫内膜VEGF及KDR的表达,FICu-IUD可抑制子宫内膜VEGF及KDR的生成.VEGF及KDR可能参与了FCu-IUD 及FICu-IUD所引起的子宫内膜微血管结构和功能的改变.     

Clinicopathologic study of vascular endothelial growth factor, thrombospondin-1, and microvessel density assessed by CD34 in patients with stage III ovarian carcinoma

Abstract.   Karavasilis V, Malamou-Mitsi V, Briasoulis E, Tsanou E, Kitsou E, Pavlidis N. Clinicopathologic study of vascular endothelial growth factor, thrombospondin-1, and microvessel density assessed by CD34 in patients with stage III ovarian carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 241–246.
The aim of the study was to investigate angiogenesis in patients with advanced-stage ovarian carcinoma. We used paraffin-embedded tumor tissues from 33 patients diagnosed with FIGO III ovarian cancer who had optimal surgery and received platinum-based chemotherapy. The tissue expression of CD34, vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1) was assessed immunohistochemically. CD34 stained hot spot areas were used to evaluate tumor microvessel density (MVD). VEGF and TSP-1 were assessed by semiquantitative methods. The studied molecules were investigated for relationship with standard clinicopathologic parameters. MVD count was high: median value of 39, range 12–143 microvessels/mm². VEGF was present in all cases and stained strong in 91%. Stroma staining for TSP-1 was weak in 79% of the cases, strong in 6%, and absent in five (15%). We did not find correlations between the three studied markers and histologic type or tumor grade. MVD score did not relate to VEGF or TSP-1. We only observed a trend toward a longer survival in patients with tumors expressing high TSP-1 (60 vs. 36 months, P = 0.1). Proangiogenetic factor VEGF is highly expressed in advanced-stage ovarian carcinomas. The findings of this study may offer support for considering VEGF-targeted therapeutics in ovarian cancer treatment research.     

上皮性卵巢癌血管内皮生长因子的表达与肿瘤内微血管密度的相关性研究

目的 :探讨上皮性卵巢癌组织中血管内皮生长因子 (VEGF)是否与肿瘤内微血管密度 (MVD)、淋巴转移等临床病理学因素存在相关性。方法 :以多克隆抗VEGF抗体和单克隆抗CD34抗体分别标记 4 5例FIGOⅠ～Ⅳ期上皮性卵巢癌术后标本的VEGF和MVD。用彩色图像病理分析系统测定VEGF的相对含量 ,MVD采用人工计数。分析VEGF与MVD、肿瘤期别、组织学类型、腹水量以及淋巴转移的关系。结果 :(1)VEGF的平均吸光度为 0 .178± 0 .14 9(中位数 0 .16 7)。MVD值平均为 72 .2 6± 5 8.5 2 /mm2 (中位数 6 8.4 7/mm2 ) ;(2 )VEGF表达水平与MVD之间存在显著相关性 (r =0 .92 6 ,P <0 .0 1) ;(3)盆腔淋巴转移(n =12 )VEGF平均吸光度 (0 .193± 0 .15 3)显著高于无盆腔淋巴转移组 (n =32 )的 0 .138± 0 .0 90 ,(P <0 .0 5 )。不同期别 ,组织学类型和腹水量之间的VEGF表达强度无显著差异(P >0 .0 5 )。结论 :VEGF表达与上皮性卵巢癌血管生成的增强密切相关     

Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density

OBJECTIVE: Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer. METHODS: Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors. RESULTS: Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05). CONCLUSION: Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.     

Fascin, an actin-bundling protein expression in cervical neoplasms

PURPOSE OF INVESTIGATION: Our objectives were (1) to examine expression of fascin in cervical tissues with chronic inflammation, intraepithelial neoplasms and invasive carcinomas, and (2) to investigate the role of fascin on endothelial migration and angiogenesis in cervical neoplasms. METHODS: In this study we investigated by means of immunohistochemistry fascin expression in 92 cervical biopsy samples representative of chronic inflammation (n=13), squamous intraepithelial lesions (SILs, n = 33) and invasive carcinomas (n = 46). RESULTS: Various degrees of fascin expression were observed in 94% of the samples of SILs, in 67% of the samples of invasive cervical carcinoma and in 69% of the samples of chronic inflammation. Total epithelial fascin scores of samples were significantly higher in high-grade (H)SILs compared to low-grade (L)SILs, invasive carcinoma and chronic inflammation of the cervix (p < 0.05). Mean microvessel count was 55.00 +/- 5.17 in HSILs, 40.76 +/- 3.57 in LSILs, 37.11 +/- 2.91 in carcinoma and 25.69 +/- 3.98 in chronic inflammation. We found a significantly higher microvessel count in HSILs compared to invasive carcinoma and chronic inflammation (respectively, p = .004, p = .000). CONCLUSION: Epithelial fascin expression up-regulated when the malignant tumor cell phenotype had occurred in the cervix. Similarly, microvessel count increased with the beginning of cervical tumorigenesis.     

Expression of von Willebrand's factor,CD34, CD31, and vascular endothelial growth factor in uterine leiomyomas

OBJECTIVE: To compare the vascular parameters of uterine leiomyomas and normal myometrium, to correlate these parameters with vascular endothelial growth factor (VEGF) expression and clinical/pathological parameters, and to compare vascular parameters according to the endothelial markers used.DESIGN: An immunohistochemical technique was applied to formalin-fixed paraffin-embedded tissue samples, using antibodies against von Willebrand's factor (FvW), CD34, CD31, and VEGF. The intratumoral vascular area (VA), microvessel density (MVD), and vascular luminal area (VLA) were determined with an image analyser.SETTING: University teaching hospital.PATIENT(S): Thirty-two patients with uterine leiomyomas underwent conservative surgery. Twenty leiomyoma-free patients undergoing hysterectomy were the controls.INTERVENTION(S): Immunohistochemical and morphometrical analysis.MAIN OUTCOME MEASURE(S): Measurements of VA, MVD, and VLA.RESULT(S): The CD34 labeling showed decreased VA in myomas compared with myometrium. Decreased MVD and an increased VLA in myomas were found with FvW and CD34 labeling. The VA, MVD, and VLA were not related to VEGF expression or to clinical/pathological parameters. Similar results for VA and MVD were obtained with FvW and CD34 labeling.CONCLUSION(S): Leiomyomas have a smaller vascular area, a lower microvessel density, and a higher vascular luminal area than normal myometrium.     

新辅助化疗对宫颈癌微血管密度及血管内皮生长因子的影响

目的 :研究进展期宫颈癌新辅助化疗 (NACT)前后微血管密度 (MVD)及血管内皮生长因子 (VEGF)的改变 ,探讨新辅助化疗对宫颈癌治疗的意义。方法 :手术前行NACT的宫颈癌患者 37例为研究组 (NACT组 ) ,直接手术的 2 0例患者为对照组。应用免疫组化方法检测宫颈癌组织的MVD和VEGF的表达 ,分析其改变与NACT的关系和意义。结果 :(1 )NACT的总有效率为 62 .2 % ;(2 )NACT组在化疗前与直接手术组MVD和VEGF的表达差异无显著性 ;(3)NACT有效者的MVD和VEGF的表达明显降低 ,无效者则无明显变化 ;(4)NACT后宫颈腺癌和鳞癌的MVD和VEGF表达率无显著差异。结论 :NACT对进展期宫颈癌有效 ,NACT有效者的MVD和VEGF表达明显减低 ,MVD和VEGF可以作为NACT的客观评价新指标     

Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma

The aim of the study was to test the prognostic value of the microvessel density (MVD) within the tumor and the vascular endothelial growth factor (VEGF) expression on clinical response to chemotherapy, on brief disease-free interval, and on cause-specific survival in advanced ovarian serous carcinoma. We evaluated 83 ovarian carcinomas homogeneous for stage, type and grade histologic, surgical, and chemotherapeutic treatment. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log-rank test. A multivariate analysis (Cox-proportional hazards model) was used to determine the independent effect of each variable on prognosis. Overall 60 and 120 months cause-specific survival rates were 27.7% and 2.4%, respectively. The brief disease-free interval rate was 66.2%. In univariate analysis, VEGF (P = 0.0001 and P = 0.016), MVD (P < 0.0005), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.01 and P < 0.0005, respectively) were associated with survival and brief disease-free interval, and the residual tumor was associated with survival (P = 0.021). In multivariate analysis, the factors that were independent predictors of survival were MVD (P < 0.0005), VEGF (P = 0.027), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.013). Moreover, MVD was an independent predictor also of brief disease relapse (P = 0.001). Both MVD and VEGF were correlated with clinical response to chemotherapy (P = 0.01 and P = 0.037). Our data suggest that MVD and VEGF may have prognostic significance in advanced ovarian serous carcinoma.     

Angiogenic properties of carcinoma in situ and microinvasive carcinoma of the uterine cervix

Neovascularization is a critical step in the growth, progression and metastasis of tumors. The degree of angiogenesis may correlate with disease stage and provide prognostic information in various neoplasms. Microvessel density was studied in 24 patients with severe cervical intraepithelial neoplasias, 15 patients with microinvasive carcinomas (International Federation of Gynecology and Obstetrics IA1) and 15 healthy controls who had undergone hysterectomy for benign conditions. The microvessel density (MVD) in microinvasive squamous cell carcinomas was 40 +/- 2.42 (mean +/- SD) and in squamous carcinomas in situ (CIS) 20.41 +/- 2.29 (p < 0.05). Among patients with CIS and controls (13.33 +/- 1.59) there was also a significant difference in the number of vessels (p < 0.05). No significant correlation was found in relation to depth of invasion and histological grade of the microinvasive carcinomas. It is concluded that microinvasive squamous cell cervical carcinoma is an angiogenetic disorder and it seems that the onset of angiogenesis is an early event, usually in a preinvasive stage.     

应用组织芯片技术研究卵巢癌组织中缺氧诱导因子1α与血管生成的关系

目的　探讨缺氧诱导因子 1α(hypoxiainduciblefactor 1α ,HIF 1α)在卵巢癌组织中的表达及其与血管生成的关系。方法　联合应用组织芯片和原位杂交、免疫组化技术 ,检测 2 95份卵巢上皮性肿瘤 (其中卵巢癌 2 38份、交界性卵巢肿瘤 19份、良性卵巢肿瘤 38份 )及 13份正常卵巢组织中HIF 1αmRNA和血管内皮生长因子 (VEGF)的表达情况 ,以CD3 4 单克隆抗体标记血管内皮细胞来检测微血管密度 (MVD)。结果　卵巢癌、交界性卵巢肿瘤和良性卵巢肿瘤、正常卵巢组织中HIF 1αmRNA的阳性表达率分别为 81 9%、4 2 1%、13 2 %和 0。交界性卵巢肿瘤和卵巢癌组织中HIF 1αmRNA的表达高于正常卵巢和良性卵巢肿瘤 ,卵巢癌高于交界性肿瘤 ,差异均有统计学意义 (P <0 0 1)。卵巢癌组织中HIF 1αmRNA的表达与手术病理分期和病理类型无关 (P >0 0 5 ) ,而与病理分级呈正相关 (r=0 2 4 6 ,P <0 0 1)。卵巢癌组织中HIF 1αmRNA表达与VEGF表达 (r =0 2 0 6 ,P =0 0 1)和MVD计数 (r =0 4 5 1,P <0 0 1)均呈显著正相关。结论　卵巢癌组织过度表达HIF 1αmRNA ,并通过诱导VEGF促进肿瘤的新生血管形成。     

两种类型子宫内膜癌的血管生成研究

目的 :研究两种类型 (伴有内膜过度增生和不伴有内膜过度增生 )内膜癌血管生成的差别。方法 :诊刮或子宫切除内膜癌标本 94份 ,用LSAB免疫组化法以CD34标记血管内皮细胞计数微血管密度 (MVD) ,检测并比较碱性成纤维细胞生长因子 (FGF - 2 )在两种不同类型内膜癌中的表达。结果 :37份 (39.4 % )在内膜癌邻近部位有内膜过度增生。在有过度增生型内膜癌中 ,MVD低 (≤ 6 0 / 2 0 0倍光镜 )的例数所占比例 (70 .3% )多于无过度增生型 (42 .1% ) (P <0 .0 1)。FGF - 2阳性率在有过度增生的内膜癌组 (43.2 % )低于无过度增生组 (6 4 .9% ) (P <0 .0 5 )。FGF - 2阳性组的平均MVD(6 1.2 9± 6 .38)高于FGF - 2阴性组 (5 8.6 4± 5 .17) (P <0 .0 5 )。结论 :无子宫内膜过度增生的内膜癌患者血管生成增加 ,而FGF - 2有促进内膜癌血管生成的作用     

基质金属蛋白酶-9及基质金属蛋白酶组织抑制物-1表达失衡与宫颈癌局部肿瘤血管生成的关系

目的 :探讨基质金属蛋白酶 - 9(MMP 9)和基质金属蛋白酶组织抑制物 - 1(TIMP 1)在宫颈癌局部肿瘤血管生成中的作用。方法 :采用免疫组织化学SP法检测 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中MMP 9和TIMP 1的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )。结果 :从NCE组到CIN组再到ICC组 ,MMP 9的阳性表达率显著升高 (P <0 0 5 )而TIMP 1未见升高 (P >0 0 5 ) ,并且TIMP 1在ICC组的阳性表达率显著低于MMP 9(P <0 0 1)。MMP 9在ICC组中表达与MVD显著正相关 (r =0 2 87,P <0 0 5 ) ,而TIMP 1与MVD无显著相关性 (r=0 195 ,P >0 0 5 )。宫颈癌中MMP 9表达高于TIMP 1者 ,其MVD显著高于MMP 9表达低于TIMP 1者 (P <0 0 5 )。结论 :MMP 9和TIMP 1表达失衡可能在宫颈癌局部肿瘤血管生成中起重要作用 ,MMP 9表达增强而TIMP 1表达降低 ,其血管生成能力可能显著增强 ,但并非唯一决定因素。检测宫颈癌中MMP 9和TIMP 1表达对进一步了解宫颈癌局部血管生成情况有一定的应用价值。     

肿瘤抑素抗血管活性相关肽对宫颈癌Hela细胞生长和转移抑制作用的实验研究

目的研究改造后的血管生成抑制相关肽（21肽）抗血管生成活性及对人宫颈癌Hela细胞皮下移植裸鼠模型的抑制作用,探讨其抑瘤作用机制。方法2005年8月至2006年2月哈尔滨医科大学第一临床医学院进行Hela细胞株皮下接种裸鼠造模,21肽治疗3周后,处死动物剥离肿瘤,称重并计算抑瘤率。免疫组化方法检测21肽对肿瘤组织的微血管密度（MVD）、增殖细胞核抗原（PCNA）和血管内皮生长因子（VEGF）的影响。结果21肽组平均抑瘤率可达51.89%,肿瘤组织微血管密度明显降低,与对照组比较差异有统计学意义（P〈0.05）;21肽组肿瘤组织的PCNA、VEGF呈低表达,与对照组比较差异有统计学意义（P〈0.05）。结论21肽具有显著的抗血管生成活性,可明显地抑制裸鼠宫颈癌细胞的生长,其抑制宫颈癌的作用机制可能与其降低新生血管形成和调解血管生成相关因子的表达有关。