转化生长因子β1及其Ⅱ型受体在卵巢肿瘤中的表达及意义

目的探讨转化生长因子β1(TGF-β1)及其Ⅱ型受体(TGFβR-Ⅱ)在卵巢肿瘤中的表达及其意义。方法1998年7月至2001年12月哈尔滨医科大学第一临床医学院,采用SP免疫组化染色方法,对30例卵巢癌,30例卵巢良性上皮性肿瘤及30例正常卵巢组织中TGF-β1、TGFβR-Ⅱ的表达进行分析。结果卵巢癌组TGF-β1阳性率明显高于正常卵巢组(P<0·01),且二者的强阳性率比较差异有非常显著性意义(P<0·01);卵巢良性上皮性肿瘤中TGF-β1阳性率与正常卵巢组比较,两者的阳性率、强阳性率之间比较差异均无显著性意义(P>0·05)。卵巢癌组TGFβR-Ⅱ阳性率低于正常卵巢组(P<0·05),且两者的强阳性率之间差异有非常显著性意义(P<0·01);卵巢良性上皮性肿瘤中TGFβR-Ⅱ阳性率与正常卵巢组比较,两者的阳性率、强阳性率之间差异均无显著性意义(P>0·05),与卵巢癌组比较,两者的阳性率之间差异有显著性意义(P<0·05),但强阳性率之间差异无显著性意义(P>0·05)。结论在卵巢癌中TGF-β1呈过度表达,使得其抑制癌细胞生长的作用丧失。在卵巢癌中TGFβR-Ⅱ失表达,使肿瘤细胞有效地逃避了机体的抑制。     

整合素连接激酶在卵巢肿瘤组织中的表达及意义

目的探讨整合素连接激酶（ILK）在正常卵巢、卵巢良性肿瘤、卵巢交界性肿瘤、卵巢癌组织中的表达及其临床意义。方法1999年1月至2006年12月在沧州中西医结合医院采用免疫组化SP法检测正常卵巢组织10例,良性卵巢肿瘤20例,交界性肿瘤28例,卵巢癌86例中整合素连接激酶的表达。结果ILK蛋白在卵巢癌、交界性肿瘤、良性肿瘤组织中的表达差异有显著性意义（P〈0.05）。结论ILK在卵巢恶性肿瘤的发生发展中起重要作用,检测ILK的表达有助于判断肿瘤的生物学行为及预后。     

可溶型Fas在卵巢肿瘤中的表达及共生物学意义分析

目的 检测Ｆａｓ基因在各类人卵巢组织标本和卵巢癌细胞系中的表达并分析其对肿瘤发生的意义。方法 应用免疫组织化学染色和Ｗｅｓｔｅｒｍ印迹杂交技术,对８例非瘤卵巢组织、１８例良性和２３例卵巢癌标本以及３株卵巢癌细胞系中Ｆａｓ基因的表达情况加以分析,观察抗Ｆａｓ抗体对卵巢癌细胞体外生长的影响。结果 Ｆａｓ在非瘤卵巢组织中的阳性表达率是１２．５％,在良性肿瘤为８９％,在浆液性囊腺癌和粘液性囊腺癌分别为１０     

可溶型Fas在卵巢肿瘤中的表达及其生物学意义分析

目的　检测Fas基因在各类人卵巢组织标本和卵巢癌细胞系中的表达并分析其对肿瘤发生的意义。方法　应用免疫组织化学染色和Western印迹杂交技术 ,对 8例非瘤卵巢组织、18例良性和 2 3例卵巢癌标本以及 3株卵巢癌细胞系中Fas基因的表达情况加以分析 ,观察抗Fas抗体对卵巢癌细胞体外生长的影响。结果　Fas在非瘤卵巢组织中的阳性表达率是 12 5 % ,在良性肿瘤为 89% ,在浆液性囊腺癌和粘液性囊腺癌分别为10 0 %和 86 % ;3株卵巢癌细胞系Fas均呈阳性表达。Western印迹杂交显示 :卵巢癌细胞产生的Fas蛋白以分子质量 40ku的可溶型 (sFas)为主 ,伴少 (痕 )量的 43ku膜型 (mFas)。用最高浓度为 2 0 0 μg/L的抗Fas抗体处理 3株卵巢癌细胞系 ,未能抑制靶细胞生长和诱导凋亡。结论　sFas普遍存在于卵巢肿瘤和癌细胞系。缺乏mFas可能是影响卵巢癌细胞凋亡和 (或 )化疗耐受性的遗传学因素之一     

Wnt信号通路成分β-catenin和APC在卵巢肿瘤中的表达及意义

目的:探讨Wnt信号通路成分β-catenin和APC基因在上皮性卵巢癌的表达及意义。方法:应用免疫组织化学染色SABC法检测49例卵巢癌(24例浆液性囊腺癌、15例黏液性囊腺癌、10例子宫内膜样癌),10例交界性卵巢肿瘤及16例良性卵巢肿瘤中β-catenin、APC基因的表达,分析其相关性。结果:卵巢癌中β-catenin的异常表达率明显高于卵巢交界性肿瘤和卵巢良性肿瘤,差异有统计学意义(P0.05)。卵巢癌中APC基因的阴性表达率明显高于卵巢良性肿瘤,差异有统计学意义(P0.05),而与卵巢交界性肿瘤无显著差异(P0.05)。卵巢癌中APC基因的阴性表达与β-catenin的异常表达无相关性(r=0.0429,P0.05)。2例卵巢子宫内膜样癌中可见β-catenin胞核表达,但不伴有APC基因的阴性表达。结论:卵巢癌中Wnt信号通路中的成分发生变化,但其激活机制可能有别于Wnt信号通路的传统激活机制,可能在卵巢子宫内膜癌的发生中发挥作用。     

CD44S在卵巢肿瘤中的表达

ＣＤ４４Ｓ在卵巢肿瘤中的表达曲焦书竹陈斌其师宜荃张新莹郭月梅ＣＤ４４是一类分布极为广泛的细胞表面跨膜糖蛋白，主要参与细胞－细胞、细胞－基质间特异性粘连过程［１］。特别是ＣＤ４４标准型（ＣＤ４４Ｓ），是透明质酸（ＨＡ）的主要表面受体［２］，能介导细...     

CD44在卵巢肿瘤组织中的表达及临床意义

为探讨CD44在卵巢肿瘤组织中的表达及其临床意义。我们采用RNA逆转录-聚合酶链反应（RT-PCR）方法,对卵巢肿瘤及对照组织中的CD44标准型（CD44S幻变异型（CD44V）以及变异型中的一些亚型（CD44V3、V6、V9）的表达进行检测。现报道如下。一、材料与方法1．标本来源及临床资料：     

肿瘤坏死因子基因在卵巢肿瘤中的表达

以地高辛配基记的肿瘤坏死因子－ａｃＤＮＡ为探针，采用原位杂交技术对５４例卵巢肿瘤及１０例正常卵巢组织新鲜标本制成的冰冻切片，进行肿瘤坏死因子基因检测，观察卵巢肿瘤细胞及肿瘤浸润淋巴细胞ＴＮＦ基因的表达。结果：卵巢癌细胞及ＴＩＬ的ＴＮＦ基因阳性率明显高于卵巢交界性和良性肿瘤的瘤细胞及其ＴＩＬ；临床分期赵晚，癌细胞内ＴＮＦ基因的阳性纺赵高，而ＴＩＬ内ＴＮＦ基因阳性率赵低，表明：卵巢肿瘤细胞及ＴＩＬ内Ｔ     

上皮性卵巢肿瘤cyclin B1和p27的表达及其意义

目的:探讨cyclin B1和p27在上皮性卵巢肿瘤发生、发展及预后中的作用。方法:应用免疫组化S-P法检测正常卵巢(20例)、良性上皮性卵巢肿瘤(20)及恶性上皮性卵巢肿瘤(20例)中cyclin B1和p27的表达,分析其表达水平与肿瘤恶性程度、临床分期及淋巴转移间的关系。结果:cyclin B1在恶性上皮性卵巢肿瘤中的表达水平高于正常卵巢和良性肿瘤,差异有显著性(P<0.05);p27在正常卵巢、良性肿瘤和恶性肿瘤中的阳性表达呈显著性递减趋势(P<0.05);cyclin B1表达与肿瘤的临床分期及淋巴转移显著相关(P<0.05)。结论:cyclin B1高表达和p27低表达,可能与卵巢肿瘤的发生、发展密切相关。     

上皮性卵巢肿瘤eyelin B1和p27的表达及其意义

目的：探讨cyclinB1和p27在上皮性卵巢肿瘤发生、发展及预后中的作用。方法：应用免疫组化S—P法检测正常卵巢（20例）、良性上皮性卵巢肿瘤（20）及恶性上皮性卵巢肿瘤（20例）中cyclinB1和p27的表达，分析其表达水平与肿瘤恶性程度、临床分期及淋巴转移间的关系。结果：cyclinB1在恶性上皮性卵巢肿瘤中的表达水平高于正常卵巢和良性肿瘤，差异有显著性（P〈0．05）；p27在正常卵巢、良性肿瘤和恶性肿瘤中的阳性表达呈显著性递减趋势（P〈0．05）；cyclinB1表达与肿瘤的临床分期及淋巴转移显著相关（P〈0．05）。结论：cyclinB1高表达和p27低表达，可能与卵巢肿瘤的发生、发展密切相关。     

Aurora-Ipl1激酶1 mRNA在卵巢恶性肿瘤组织中的表达及其意义

目的 :研究卵巢恶性肿瘤组织中Aurora Ipl1激酶 1(AIK1)mRNA的表达 ,探讨AIK1基因与卵巢肿瘤发生的关系。方法 :采用半定量逆转录聚合酶链反应 (RT PCR)检测 2 7例卵巢恶性肿瘤、15例卵巢良性肿瘤或瘤样病变、12例正常卵巢组织中AIK1mR NA。结果 :AIK1mRNA在卵巢恶性肿瘤组织中的表达显著高于卵巢良性病变 (P <0 .0 5 )及正常组织 (P <0 .0 5 )。AIK1mRNA的表达与年龄、组织学类型、分期、腹水等无关 (P >0 .0 5 )。结论 :卵巢恶性肿瘤中AIK1mRNA表达上调 ,提示AIK1基因与卵巢癌发生有关     

CyclinD1、C-erbB2及bcl-2基因在卵巢上皮性肿瘤中的表达及其临床意义

目的 :检测癌基因CyclinD1、C erbB2及bcl 2在卵巢上皮肿瘤中的表达 ,探讨它们在卵巢肿瘤发生、发展中的作用及临床、病理意义。方法 :应用免疫组化SP法检测72例恶性卵巢肿瘤、12例交界性卵巢肿瘤、2 1例良性肿瘤及 10例正常卵巢组织中Cy clinD1、C erbB2及bcl 2基因的表达情况。结果 :1.卵巢恶性、交界性及良性肿瘤中Cy clinD1阳性率依次为 2 7.78%、33.3%、9.5 2 %。恶性及交界性肿瘤阳性率明显高于良性肿瘤 ,其阳性率与组织学分级呈负相关 ,而与患者年龄、临床分期、组织学类型无关 ;2 .卵巢恶性、交界性及良性肿瘤中C erbB2的阳性率依次为 5 6 .9%、4 1.6 7%、14.2 8%。恶性及交界性肿瘤阳性率明显高于良性肿瘤 ,差异有显著性。C erbB2阳性表达在组织分化差及期别晚的肿瘤中较分化好、期别早者高 ;3.卵巢恶性、交界性、良性肿瘤中bcl 2的阳性表达率依次为 6 3.89%、5 0 %、2 8.5 %。恶性及交界性肿瘤与良性肿瘤之间的表达差异有显著性。组织分化差、期别早的肿瘤中bcl 2的阳性率较分化好、期别晚者高 ;4 .两种及两种以上基因同时表达率 (5 1.4 % )显著高于单基因表达 (2 7.79% )。CyclinD1与C erbB2基因表达呈负相关。结论 :CyclinD1、C erbB2及bcl 2基因在卵巢癌发生、发展中起重要作用 ,表明细胞?     

卵巢上皮性癌组织中水通道1蛋白和mRNA的表达及其临床意义

目的探讨水通道1(AQP1)蛋白和mRNA在卵巢上皮性癌组织中的表达及其临床意义。方法采用免疫组化法、蛋白印迹法和RT-PCR技术检测35例卵巢上皮性癌、15例卵巢交界性上皮性肿瘤、15例卵巢良性上皮性肿瘤组织中AQP1蛋白和mRNA的表达,并以13例正常卵巢组织为对照。结果AQP1蛋白主要表达于卵巢上皮性肿瘤和正常卵巢组织的毛细血管及小血管内皮细胞膜,卵巢上皮性癌和卵巢交界性上皮性肿瘤组织中AQP1蛋白表达水平分别为0.39±0.12和0.43±0.21,AQP1mRNA表达水平分别为0.93±0.51和0.95±0.34,均明显高于卵巢良性上皮性肿瘤和正常卵巢组织(AQP1蛋白表达水平分别为0.27±0.13和0.24±0.13,AQP1mRNA表达水平分别为0.51±0.41和0.34±0.29;P<0.05)。卵巢上皮性癌患者腹水量≥1000ml者其癌组织中AQP1蛋白表达水平为0.46±0.13、AQP1mRNA表达水平为1.25±0.57,明显高于腹水量为1～499ml者(AQP1蛋白表达水平为0.35±0.11,AQP1mRNA表达水平为0.75±0.45;P<0.05);卵巢上皮性癌组织中AQP1蛋白和mRNA表达与其手术病理分期、病理类型、病理分级和有无淋巴结转移无关(P>0.05)。结论AQP1蛋白和mRNA过度表达在卵巢上皮性癌发生、发展中起一定的作用,是其腹水形成的原因之一。     

The prognostic significance of elongation factor eEF1A2 in ovarian cancer

BackgroundCervical embryonal rhabdomyosarcoma (ERMS) mostly affects young girls. The current treatment protocols are based on trials done on patients under 21 years old. ERMS in women over 40 is rare, and studies on treatment and outcome are limited.CaseWe report a case of a 41 year-old woman with cervical ERMS who was treated with radical hysterectomy followed by chemotherapy. She is currently disease-free.ConclusionCervical ERMS in women over the age of 40 can be treated using protocols established for the pediatric population.     

Cyclooxygenase-2 expression in borderline ovarian tumors

OBJECTIVES: The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors. METHODS: Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive. RESULTS: Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22). CONCLUSIONS: COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis.     

卵巢癌胸苷磷酸化酶及其mRNA的表达及临床意义

目的 :研究卵巢肿瘤中胸腺嘧啶脱氧核苷磷酸化酶 (TP)及其mRNA的表达与微血管密度 (MVD)的关系及其临床意义。方法 :卵巢良性肿瘤 2 1例 ,卵巢癌 35例。术后肿瘤组织用免疫组化法检测TP及factorⅧ的表达 ,计算MVD ;用原位杂交 (ISH)法检测TPmRNA。结果 :卵巢癌TP、TPmRNA的阳性率分别为 71.4 %和 4 8.5 % ,明显高于良性者的 38.0 %和 2 8.0 % (P <0 .0 0 1,P <0 .0 5 )。有淋巴结转移者TP、TPmRNA的表达率分别为10 0 %和 77% ,明显高于无淋巴结转移者的 65 .3%和 38.4 % (P <0 .0 5 )。卵巢癌TP、TPmRNA表达与病理组织类型、细胞分化程度、临床期别、患者腹水多少无关。卵巢癌的MVD平均为 2 8.2 7± 2 2 .34,明显高于良性者的 12 .5 3± 16.5 8(P <0 .0 1)。TP与MVD具有相关性 ,TP阳性者MVD明显增高。结论 :TP和TPmRNA在卵巢癌中表达增强 ,是卵巢癌重要的促血管生成因子 ,TP表达与淋巴结转移、患者预后有关     

Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia

Objective

To investigate the placental expression of angiopoietin (Ang)-1, Ang-2 and their receptor, Tie-2, in preeclampsia (PE) with or without intrauterine growth restriction (IUGR).

Methods

Case-control study including placentas from 28 PE pregnancies, 30 PE-IUGR pregnancies and 40 controls. The expression status of the genes was evaluated by quantitative real-time PCR.

Results

In both PE and PE-IUGR groups, compared to the control group, there was significantly higher expression of Ang-2 (p < 0.001) and Tie-2 (p = 0.008) and lower expression of Ang-1 (p = 0.001). The magnitude of the difference was similar for Ang-1 for both groups, whereas the magnitude of the differences was higher for Ang-2 and Tie-2 in PE-IUGR group compared to controls. Ang-2 and Tie-2 were correlated in both PE (r = 0.8602, p < 0.001) and PE-IUGR (r = 0.6342, p < 0.001) groups. In PE-IUGR group, Ang-1 was associated to Ang-2 (r = 0.3458, p = 0.0452) and Tie-2 (r = 0.4448, p = 0.0084). Log₁₀Ang-1 but not Ang-2 was gestational age dependent (R2 = 0.40, p < 0.001). After conversion in Multiples of the Median (MoM) log₁₀ MoM Ang-1 was reduced in the PE group (mean = −0.8181, p < 0.001) and the PE-IUGR group (mean = −1.2583, p < 0.001) compared to control group (mean = −0.0924).

Discussion

We have demonstrated increased placental expression of Ang-2 and Tie-2 along with lower expression levels of Ang-1 in pregnancies with PE and PE-IUGR.

Conclusion

The angiopoietin axis seems to be disrupted in PE pregnancies. Whether the results of this study represent the angiogenic imbalance observed in PE pregnancies or they are part of the pathophysiology of this condition has to be further investigated.     

Gelatinases and their tissue inhibitors in ovarian tumors; TIMP-1 is a predictive as well as a prognostic factor

OBJECTIVE: In the present study, the significance of circulating matrix metalloproteinases -2 and -9 (MMP-2, MMP-9), as well as their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in ovarian cancer were studied to assess the possibility of using them in clinical decision-making. METHODS: We measured, prior to primary surgery, the concentrations of these proteins in serum samples of 115 patients with an ovarian tumor: 63 with cancer, 6 with a low malignant potential tumor, and 46 with a benign tumor. The measurements were performed with enzyme-linked immunosorbent assays (ELISA). The results were compared to clinicopathological data. RESULTS: A high serum concentration of TIMP-1 at diagnosis was found to correlate with the malignant phenotype of an ovarian tumor. Within malignant neoplasias, high circulating TIMP-1 correlated to the aggressive phenotype and unfavorable prognosis. An association was found between a high serum level of TIMP-1 and an advanced stage of the disease, a residual tumor>2 cm, poor response to cytotoxic treatment, shorter recurrence free time, and shorter cancer-related overall survival. No statistically significant correlation was found between the circulating gelatinases (MMP-2, MMP-9) or TIMP-2 and the clinicopathological factors. However, a tendency for better survival with high serum concentration of TIMP-2 or MMP-2 was observed. CONCLUSION: We conclude that an elevated preoperative serum TIMP-1 concentration correlates to the aggressive behavior of ovarian cancer.     

卵巢上皮性肿瘤中细胞周期素D1蛋白与p16蛋白的表达及其临床意义

目的　探讨细胞周期素D1蛋白 (cyclinD1)与 p16蛋白在卵巢上皮性肿瘤中的表达及临床意义。 方法　 1998年 1月至 2 0 0 0年 1月采用免疫组化SP法 ,检测恶性、交界性、良性卵巢上皮性肿瘤、正常卵巢组织中的cyclinD1蛋白和p16蛋白的表达。结果　cyclinD1蛋白、p16蛋白表达的阳性率分别为恶性 5 0 %和 4 0 %、交界性30 %和 5 0 %、良性卵巢上皮性肿瘤 0和 80 %、正常卵巢组织中 0和 90 %。恶性卵巢上皮性肿瘤与良性卵巢上皮性肿瘤及正常卵巢组织之间比较 ,cyclinD1蛋白的表达差异有显著性意义 (P <0 0 1) ,p16蛋白的表达差异有显著性意义 (P <0 0 5 )。在恶性程度较高 ,组织分化差 ,晚期的恶性卵巢上皮性肿瘤中cyclinD1蛋白表达率高 ,p16蛋白的表达率低。相关性分析显示 ,cyclinD1蛋白与 p16蛋白的表达呈负相关。 结论　cyclinD1蛋白的过度表达与 p16蛋白表达的缺失在恶性卵巢上皮性肿瘤的发生、发展中起一定作用 ,二者可能存在相互抑制机制。