葡萄糖转运蛋白1在卵巢上皮性癌组织中的表达及其与碱性成纤维生长因子、增殖细胞核抗原表达的关系

目的探讨卵巢上皮性癌组织中葡萄糖转运蛋白1(GLUT1 )的表达及其与碱性成纤维生长因子(bFGF)、增殖细胞核抗原(PCNA)表达的关系。方法采用免疫组化链霉菌抗生物素蛋白过氧化物酶连接法(SP法)检测6例正常卵巢、20例卵巢良性肿瘤、7例卵巢交界性肿瘤和44例卵巢上皮性癌组织中GLUT1、bFGF、PCNA的表达,并对GLUT1 与bFGF、PCNA表达的关系进行了相关性分析。结果GLUT1 在正常卵巢、卵巢良性肿瘤组织中不表达,而在卵巢交界性肿瘤及卵巢上皮性癌组织中阳性表达率分别为6 /7、91% (40 /44),卵巢上皮性癌组织中GLUT1 的阳性表达率明显高于卵巢交界性肿瘤组织(P<0 05)。卵巢上皮性癌组织中GLUT1 的阳性表达率与病理分级、手术病理分期、远处转移、淋巴结转移均呈明显正相关(P<0 01),而与病理类型无关(P=0 513)。在卵巢上皮性癌组织中,bFGF阳性表达25例,其中3例GLUT1 染色强度为( ++)、22例( +++);阴性表达19例,其中4例GLUT1 染色强度为( -)、4例( +)、8例( ++)、3例( +++),bFGF阳性表达者GLUT1 染色强度高于bFGF阴性表达者,差异有统计学意义(P<0 01)。GLUT1 染色强度与PCNA标记指数相关,GLUT1 染色强度为( +)、( ++)、( +++)的卵巢上皮性癌组织的PCNA标记指数分别为0 40、0 43、0 69,GLUT1 染色强度为( +++)的卵巢     

卵巢上皮性肿瘤中人类软骨糖蛋白39和癌胚抗原125的表达及意义

目的研究卵巢上皮性肿瘤组织中人类软骨糖蛋白39(YKL-40)和癌胚抗原125(CA125)的表达,探讨其在卵巢恶性上皮性肿瘤进展中的作用机制及其临床意义。方法选取2000年3月至2004年5月在哈尔滨医科大学第一临床医学院手术标本,采用免疫组化两步法检测正常卵巢组织5例、卵巢良性肿瘤18例、卵巢交界性肿瘤14例和卵巢恶性上皮性肿瘤33例中YKL-40和CA125的表达。结果YKL-40和CA125表达水平随卵巢浆液性肿瘤恶性程度的增加而表达增高。YKL-40的表达与病理分级密切相关,但与临床分期无相关性,CA125与病理分级和临床分期均无关。结论检测YKL-40的表达可作为预测卵巢癌预后有价值的指标。     

卵巢上皮肿瘤中Erα PR及E-Cadherin的表达及意义

目的探讨卵巢上皮肿瘤各亚型中雌激素受体α(ERα)及靶蛋白孕激素受体(PR)、E-钙黏着蛋白(E-cad-herin)间表达的相关性及临床意义。方法对解放军总医院2001年1月至2006年1月经病理检查证实的67例卵巢癌标本[5例浆液性交界性腺癌、46例浆液性腺癌(SAC)、6例子宫内膜样腺癌(MAC)、5例透明细胞癌(CCA)及5例其它恶性肿瘤亚型],采用免疫组化SP法检测其ERα、PR、E-cadherin的表达情况,结合临床病理特征分析3种蛋白间表达的关系。结果(1)浆液性交界性卵巢癌、SAC、MAC、CCA中ERα表达阳性率分别为:40.0%、76.08%、66.67%、0;PR表达阳性率分别为:60.00%、82.61%、66.67%、0;E-cadherin表达阳性率分别为:100.00%、95.65%、100.00%、100.00%;SAC与CCA间ERα、PR的表达阳性率差异有统计学意义(P<0.05)。(2)E-cadherin的表达与SAC临床分期存在相关性(r=0.3610,P<0.05)。(3)SAC中,各临床病理特征(临床分期、病理学分级、年龄、淋巴转移)进行内部比较ERα、PR、E-cadherin的表达阳性率无明显差异。(4)浆液性卵巢癌中ERα、PR、E-cadherin的表达未检测出相关性(P>0.05)。结论ERα可能成为临床区分CCA和SAC的一项重要特征;E-cadherin可能在SAC的癌变过程中起重要作用,对临床诊断及预后评估具有一定的指导意义。     

卵巢恶性肿瘤超声血流指标与微血管密度的相关性研究

目的：探讨卵巢恶性肿瘤组织中彩色多普勒超声血流指标与瘤内微血管密度的相关性及其与临床分期的关系。方法：对32例卵巢恶性肿瘤术前经阴道彩色多普勒超声检查，记录瘤内最大血流速度（PSV），切除卵巢肿瘤组织后采用抗Ⅷ因子相关抗原抗体免疫组化方法检测瘤内微血管密度（IMD），记录肿瘤临床分期，分析PSV与IMD的相关性，两者与肿瘤临床分期的关系。结果：32例肿瘤中Ⅰ期7例，Ⅱ期13例，Ⅲ期9例，Ⅳ期3例；PSV与IMD间有显著相关（r=0.344,p＜0．05），临床Ⅲ-Ⅳ的PSV与IMD较Ⅰ-Ⅱ期者高。结论：卵巢恶性肿瘤内最大血流速度与微血管密度间存在相关有，有一定的临床意义。     

Ki67抗原在卵巢肿瘤组织中的表达及与临床病理参数的关系

目的 :探讨卵巢肿瘤中增殖细胞相关核抗原Ki67的表达及意义。方法 :采用流式细胞术检测Ki67抗原在 5 2例卵巢肿瘤组织中的表达。结果 :卵巢癌组织中Ki67表达显著高于卵巢良性肿瘤 (P <0 0 1)。Ki67的表达随组织学分级 (P <0 0 1)、临床分期(P <0 0 5 )的升高而增加。Ki67与卵巢癌肿瘤大小呈正相关 (r =0 4 99,P =0 0 0 6)。结论 :Ki67与卵巢癌的组织学分级、临床分期及肿瘤大小有关。     

Transvaginal color flow Doppler in the assessment of ovarian and uterine blood flow in infertile women

OBJECTIVE: To measure the flow velocity of the uterine and ovarian arteries through the menstrual cycle to determine there are changes. DESIGN: Serial measurements throughout the menstrual cycle in women attending an infertility clinic, compared with volunteers coming for annual examinations. Transvaginal ultrasound-color flow Doppler was the investigative tool. SETTING: A University Hospital ambulatory care center. PATIENTS: One hundred infertile women compared with 150 women attending the clinic for annual checkups. MAIN OUTCOME MEASURES: Changes in the resistance index of flow velocity waveforms of the uterine and ovarian arteries. RESULTS: Uterine flow velocity has a resistance index of 0.88 +/- 0.04 (2 SE) in the proliferative phase and starts to decrease the day before ovulation. A nadir of 0.84 +/- 0.04 is reached on day 18 and remains at that level for the rest of the cycle. In anovulatory cycles, these changes do not occur. A subgroup of 12 women who lacked end diastolic flow in the uterine arteries during the secretory phase were identified. Eleven of these women were infertile, 8 of whom with primary infertility. Ovarian artery flow velocity is usually detected when the dominant follicle reaches 12 to 15 mm. The resistance index is 0.54 +/- 0.04 and also declines on the day before ovulation. A nadir of 0.44 +/- 0.04 is reached 4 to 5 days later and slowly rises to 0.050 +/- 0.04 before menstruation. CONCLUSIONS: There are changes in the flow velocity patterns of the uterine and ovarian arteries during the normal ovulatory menstrual cycle. Because these changes in flow velocity begin before ovulation, it can be suspected that they may involve angiogenesis as well as hormonal factors. The changes noted in these studies are statistically significant but may be too small to be used as a diagnostic tool in the study of infertility problems.     

Power doppler ultrasound assessment of the relationship between age and ovarian perifollicular blood flow in women undergoing in vitro fertilization treatment

PURPOSE: To examine the relationship between age and ovarian perifollicular blood flow (PFBF) in women undergoing IVF. METHODS: Serial transvaginal power Doppler ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively throughout the follicular phase of ovarian stimulation in women undergoing IVF. The ultrasound assessment days were categorized according to day of hCG trigger. RESULTS: A total of 1050 ovarian follicles from 34 women undergoing one IVF treatment cycle were used for data analysis. The median age of the women was 38.5 years, ranging from 28 years to 44 years. There was a significant negative correlation between age and ovarian PFBF on the day of hCG trigger or trigger day minus 1, but not beforehand during the follicular phase. CONCLUSIONS: There was a significant negative correlation between age and ovarian PFBF in women undergoing IVF which was only observed very late in the follicular phase of ovarian stimulation.     

Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral blood flow, microvessel density, and vascular endothelial growth factor levels

OBJECTIVE: To evaluate the relationship between blood flow in the tumor assessed by color Doppler ultrasound, microvessel density, and vascular endothelial growth factor levels in endometrial carcinoma. METHODS: Forty-nine patients undergoing surgery for endometrial carcinoma were enrolled. Transvaginal color Doppler ultrasound was performed preoperatively and the lowest resistance index (RI) in the tumor was recorded for analysis. Vascular endothelial growth factor in the tumor was quantified by enzyme immunoassay. The microvessel density of the excised tumor was assessed immunohistochemically. The relationships between the corresponding RI, microvessel density, and vascular endothelial growth factor level of the tumor tissues and clinical and pathologic parameters were analyzed. RESULTS: Significantly lower RIs were noted in tumors of stage II or greater (0.37 compared with 0.50, P <.001), of high histologic grade (grade 3) (0.34 compared with 0.49, P =.004), with deep myometrial invasion (one-half depth or greater) (0.39 compared with 0.49, P =.002), with lymphovascular emboli (0.38 compared with 0.49, P <.001), or with lymph node metastasis (0.30 compared with 0.49, P <.001) compared with stage I tumors and tumors of histologic grade 1 or 2, with superficial myometrial invasion, without lymphovascular emboli, or with no lymph node metastasis. Increased vascular endothelial growth factor levels and microvessel density (x200 field) also were detected in tumors of stage II or greater (975 compared with 129 pg/mg, P =.014; and 88 compared with 61, P =.018, respectively), with lymphovascular emboli (1138 compared with 120 pg/mg, P =.002; and 86 compared with 63, P =.023), or with lymph node metastasis (1011 compared with 95 pg/mg, P <.001; and 98 compared with 61, P =. 019). Resistance index, microvessel density, and vascular endothelial growth factor levels in the tumor showed linear correlations (RI compared with microvessel density: r = -.32, P =. 03; RI compared with vascular endothelial growth factor levels: r = -.40, P =.004; microvessel density compared with vascular endothelial growth factor levels: r =.36, P =.011). CONCLUSION: Blood flow assessed by color Doppler ultrasound has histologic and biologic correlations with angiogenesis and vascular endothelial growth factor levels and might play an important role in predicting tumor progression and metastasis in endometrial carcinoma.     

Change in the ovarian environment after hysterectomy as assessed by ovarian arterial blood flow indices and serum anti-Müllerian hormone levels

Objective

The aim of this prospective study was to evaluate the changes in the ovarian environment after hysterectomy based on ovarian arterial blood flow indices and serum anti-Müllerian hormone (AMH) levels.

Study design

Ovarian arterial blood flow indices (pulsatile and resistance indices) by Doppler ultrasonography and serum AMH levels were measured at baseline and 1 week, 1 month, and 3 months after hysterectomy in 32 women ranging in age from 38 to 49 years, or at the time of screening in 21 age-matched controls. The study subjects underwent hysterectomy with conservation of both ovaries for benign diseases of the uterus (laparoscopy-assisted vaginal hysterectomy [LAVH], n = 26; and total abdominal hysterectomy [TAH], n = 6). The study subjects and controls were analyzed using a t-test or one-way analysis of variance.

Results

No differences existed in demographic profiles, ovarian arterial blood flow indices, and serum AMH levels at baseline between the hysterectomy and control groups. Ovarian arterial blood flow indices did not change before and after surgery, and there were no serial changes in the mean levels of serum AMH at each time point (1.80 ± 1.81 ng/mL [pre-operatively], 1.69 ± 1.62 ng/mL [1 week post-hysterectomy], 1.42 ± 1.34 ng/mL [1 month post-hysterectomy], and 1.52 ± 1.72 ng/mL [3 months post-hysterectomy]; p = 0.805). In addition, no significant differences in ovarian arterial blood flow indices and serum AMH levels existed between the LAVH and TAH groups.

Conclusion

This preliminary study suggests that hysterectomy does not affect the ovarian environment for up to 3 months post-operatively, as assessed by ovarian arterial blood flow indices and serum AMH levels.     

The effects of ovulation induction on ovarian epithelium dysplasia scores and Ki67 expression: an experimental study on rats

We aimed to evaluate the effects of ovulation induction on Ki67 expression and dysplasia scores of female rat ovaries. Twenty female Wistar rats were randomized either to receive 150 IU/kg human menopausal gonadotropin on estrous day 2 and 75 IU/kg human chorionic gonadotropin on the day of preestrous (induction group, n= 10) or saline as placebo on the corresponding days (control group, n= 10). After five estrous cycles bilateral oophorectomy was performed to compare the Ki67 expression and dysplasia score of the ovarian epithelium. The mean number of the cells that stained positive for Ki67 was 159.6 +/- 101.92 in the follicles, 283.4 +/- 42 in the corpus luteum, and 151 +/- 75.1 in the stroma of the study group compared to 41.8 +/- 35.6 (P= 0.03), 43.2 +/- 28.3 (P= 0.007), and 55.6 +/- 18.6 (P= 0.01), respectively, in the control group. The mean number and rate of cells that stained positive for Ki67 in the epithelium was significantly higher in the ovulation induction group (758 +/- 71 and 63 +/- 1.6%, respectively) compared to the control group (386 +/- 23, P < 0.001; and 60 +/- 1.1%, P < 0.001; respectively). The mean dysplasia score was significantly higher (9.6 +/- 1.3) in the study group compared to the control group (5.08 +/- 0.9, P < 0.001). Ovulation induction in rats resulted in increased Ki67 expression and dysplastic features in the ovarian epithelial cells.