细胞角蛋白在子宫内膜癌淋巴结中的表达及意义

目的 :研究细胞角蛋白 (cytokeratin ,CK)在子宫内膜癌淋巴结中的表达及其意义。方法 :采用免疫组化SP法检测 5 0例子宫内膜癌患者的淋巴结 2 98枚中CK的表达。结果 :(1)在转移淋巴结中 ,CK皆呈强阳性表达 ,其阳性表达率为 10 0 %。在Ⅰ、Ⅱ、Ⅲc期无转移淋巴结中 ,CK皆呈弱阳性表达 ,其阳性表达率分别为 14 .5 %、15 .1%和 16 .4 % ,3期差异无显著性 (P >0 .0 5 ) ;(2 )Ⅰ、Ⅱ期病例的淋巴结中CK表达在肌层浸润深度、组织学类型、组织学分级 3组的组内差异无显著性 (P >0 .0 5 ) ;而淋巴管浸润组的组内差异有显著性 (P <0 .0 5 ) ;(3)Ⅰ、Ⅱ期病例的淋巴结中CK表达及其他预后因素与肿瘤复发的关系 ,淋巴结中CK表达、淋巴管浸润、术后治疗 3组的组内差异有显著性 (P <0 .0 5 ) ,而肌层浸润深度、组织学类型、组织学分级 3组的组内差异无显著性 (P >0 .0 5 ) ;(4 )对子宫内膜癌的诸预后因素如肌层浸润深度、组织学类型、组织学分级、淋巴结中CK表达、淋巴管浸润、术后治疗等进行多元回归分析 ,结果显示 :淋巴结中CK表达是Ⅰ、Ⅱ期子宫内膜癌患者复发的唯一相关因素。结论 :在无转移淋巴结中 ,CK表达与淋巴管浸润有关 ,提示可能存在淋巴结微转移 ,是Ⅰ、Ⅱ期子宫内膜癌复发的独立危险因素     

雌激素受体β mRNA在子宫内膜癌中的表达及其意义

目的探讨雌激素受体β第5外显子野生型mRNA（ERβWT）及变异型mRNA（ERβE5SV）在子宫内膜癌中的表达及在子宫内膜癌发生、发展中的意义。方法取子宫内膜正常者36例及子宫内膜癌患者45例,用逆转录-聚合酶链反应（RT-PCR）扩增其组织ERβWT和ERβE5SV。将扩增产物进行电泳分析并计算ERβE5SV/ERβWT比值,用DNA测序仪对ERβE5SV和ERβWT的碱基序列进行分析。结果无论是正常子宫内膜组织还是子宫内膜癌组织,均有ERβE5SV和ERβWT的表达。ERβE5SV与ERβWT相比,缺少了激素结合区即从812～950bp之间的139个碱基。正常子宫内膜组织ERβE5SV表达均高于ERβWT,ERβE5SV/ERβWT比值平均为2.47±0.99;子宫内膜癌组织ERβE5SV表达均低于ERβWT,ERβE5SV/ERβWT比值平均为0.55±0.12,前者明显高于后者（P<0.0001）。且随病理分级的增高,ERβE5SV/ERβWT比值逐渐下降（P<0.01）。结论子宫内膜癌的发生可能与ERβWT相对于ERβE5SV的过度表达有关。     

间皮素mRNA在子宫内膜癌的表达及意义

目的:研究间皮素mRNA表达与子宫内膜癌发生、发展的关系。方法:采用半定量RT-PCR技术检测41例子宫内膜癌组织和14例正常子宫内膜组织中间皮素mR-NA的表达。结果:间皮素mRNA在子宫内膜癌和正常子宫内膜组织中的表达率分别为82.9%(34/41)与78.6%(11/14),相对含量分别为74.95±22.34、54.45±9.01。子宫内膜癌组间皮素mRNA相对含量高于正常内膜组(P=0.005)。手术病理分期Ⅲ~Ⅳ期、有淋巴结转移、深肌层浸润及低分化组的子宫内膜癌间皮素mRNA相对含量分别高于手术病理分期Ⅰ~Ⅱ期、无淋巴结转移、浅肌层浸润及高、中分化组(P分别为0.000、0.014、0.01和0.034),而与病理类型无关(P=0.219)。结论:间皮素mRNA过表达与子宫内膜癌的浸润、转移有相关性,检测其表达有助于判断子宫内膜癌的恶性程度和评估预后。     

p16基因与细胞周期素D1在子宫内膜癌中的表达及？…

研究ｐ１６和细胞周期素Ｄ１在子宫内膜癌中的表达及其临床意义。方法 采用免疫组化ＬＳＡＢ法检测４２例子宫内膜癌中ｐ１６、细胞周期素Ｄ１的表达。结果 ４２例子宫内膜癌中２０例ｐ１６表达阳性,占４７．６％,ｐ１６与子宫内膜癌的细胞分级、临床分期、肌层浸润深度有关（ｐ〈０．０５）;１７例子宫内膜癌细胞周期素Ｄ１表达阳性,占４０．５％,细胞周期素Ｄ１与子宫内膜癌的细胞分级、临床分期、淋巴结转移有关（ｐ〈０．     

Rb、CyclinD1在子宫内膜癌中的表达及临床意义

目的 研究 Rb、CyclinD1在子宫内膜癌中的表达及其临床意义。方法 采用免疫组化LSAB法检测42例子宫内膜癌中Rb、CyclinD1的表达。结果42例子宫内膜癌中19例Rb表达阳性,占45.2％,Rb与子宫内膜癌的细胞分级、肌层浸润深度有关(P<0.05);17例子宫内膜癌CyclinD1表达阳性,占40.5％,CyclinD1与子宫内膜癌的细胞分级、临床分期、淋巴结转移有关(P<0.05);Rb、CyclinD1)协同表达15例,均为晚期或低分化癌。结论Rb、CyclinD1作为细胞周期调节因子参与子宫内膜癌的发生、发展,其协同作用促进子宫内膜癌的发展,且预后不良。     

RECK与MMP-9基因在子宫内膜癌中的表达及临床意义

目的:研究RECK和MMP-9在不同子宫内膜组织中的表达,探讨两者在子宫内膜癌的发生、发展和浸润转移中的作用。方法:应用链霉菌抗生物素蛋白-过氧化酶(SP)免疫组化法检测42例子宫内膜癌组织、15例子宫内膜不典型增生组织及26例正常增生期子宫内膜组织中RECK蛋白及MMP-9蛋白表达情况。结果:与正常增生期子宫内膜组织及子宫内膜不典型增生组织相比,子宫内膜癌组织中RECK蛋白阳性表达率显著降低(χ2=9.307,P<0.05),MMP-9蛋白阳性表达率显著增高(χ2=11.438,P<0.05),RECK蛋白与MMP-9蛋白在子宫内膜癌中的表达存在明显负相关(P<0.01)。RECK蛋白的表达水平与临床分期、组织学分级、肌层浸润深度及淋巴结转移密切相关(均P<0.05);MMP-9蛋白的表达水平与临床分期、组织学分级、肌层浸润深度密切相关(均P<0.05),而与淋巴结转移无关。结论:RECK蛋白的表达缺失和MMP-9的表达可能与子宫内膜癌的发生、发展及浸润转移有关。     

子宫内膜癌Dickkopf1表达及对内膜癌侵袭力的影响

目的:研究Dickkopf1在子宫内膜癌组织和Ishikawa细胞系的表达及对子宫内膜癌侵袭力的影响。方法:应用免疫组化和免疫荧光法检测子宫内膜癌组织和Ish-ikawa细胞系中Dickkopf1的表达定位;向子宫内膜癌Ishikawa细胞系施加外源性Dickko-pf1,应用Transwellchamber法进行体外侵袭试验,检测它对内膜癌侵袭能力的影响。结果:Dickkopf1在子宫内膜癌腺上皮和基质组织中均有表达,腺上皮的表达高于基质;Dickkopf1主要表达于内膜癌细胞浆和细胞膜中;施加外源性Dickkopf1后,子宫内膜癌细胞的侵袭能力下降。结论:Dickkopf1能减弱子宫内膜癌的侵袭能力,它有望作为内膜癌的治疗靶点。     

基质金属蛋白酶及其组织抑制因子在子宫内膜癌中的表达及其意义

目的　研究基质金属蛋白酶 (matrixmetalloproteinases,MMPs) 2、9及其组织抑制因子(tissueinhibitorofmetalloproteinases ,TIMPs) 1、2在子宫内膜癌中的表达 ,探讨其与子宫内膜癌浸润转移的关系。方法　应用链霉菌抗生物素蛋白 过氧化物酶免疫组织化学方法和明胶酶谱法对 37例内膜癌及 7例绝经期妇女子宫内膜组织中MMP 2、MMP 9、TIMP 1、TIMP 2蛋白及其活性进行检测。结果　MMP 2、MMP 9及TIMP 1、TIMP 2蛋白主要分布在内膜癌细胞、血管内皮细胞及绝经期子宫内膜腺上皮细胞中 ,在间质细胞中也有少量表达。内膜癌细胞中 ,MMP 2、MMP 9及TIMP 1蛋白的表达 ,病理分级为G3内膜癌的强阳性率分别为 73%、2 0 %及 6 7% ,高于G2 (13%、0及 2 7% )、G1 者 (均为 0 ,P<0 0 5 ) ;深肌层浸润内膜癌的强阳性率分别为 6 3%、16 %及 6 8% ,高于浅肌层浸润的 8%、0及 0 (P<0 0 1) ;有淋巴结转移者的强阳性率分别为 4例中 4例、4例中 3例及 4例中 4例 ,高于无淋巴结转移者的 2 5 %、0及 2 5 % (P <0 0 5 ) ;手术病理分期为Ⅲ～Ⅳ期者强阳性率分别为 5例中 5例、5例中 3例及 5例中 5例 ,高于Ⅰ～Ⅱ期者的 30 %、0及 30 % (P <0 0 5 ) ;TIMP 2蛋白在不同病理分级、肌层浸润、淋巴结转移和手术病理分期的内膜癌细     

SLP-2 mRNA在子宫内膜癌中的表达及其意义

目的探讨SLP-2mRNA在子宫内膜癌中的表达,及其在子宫内膜癌发生、发展中的作用。方法采用半定量RT-PCR技术检测32例子宫内膜癌组织和28例正常子宫内膜组织中SLP-2mRNA的表达情况;并用表达SLP-2基因的正义和反义质粒,分别转染子宫内膜癌细胞系HEC-1B细胞,RT-PCR技术检测转染前、后HEC-1B细胞中SLP-2mRNA的表达情况,观察转染前、后细胞的形态变化;用四甲基偶氮唑蓝(MTT)法检测细胞生长情况,并绘制细胞生长曲线;流式细胞仪检测细胞周期的变化。结果子宫内膜癌组织中SLP-2mRNA的表达水平为1.6±0.7,正常子宫内膜组织为0.7±0.3,两者比较,差异有统计学意义(P<0.05)。表达SLP-2基因的正义和反义质粒成功转入HEC-1B细胞中,正义质粒转染后SLP-2mRNA表达水平增加约2.4倍,细胞生长变快,其中G1期减少12.5%,S期增高8.0%;反义质粒转染后SLP-2mRNA表达水平减少50%,细胞生长变慢,其中G1期增高10.5%,S期减少9.8%。结论子宫内膜癌中SLP-2mRNA的高表达与子宫内膜癌发生、发展有一定关系。     

淋巴结清扫术在Ⅰ期子宫内膜癌中的意义

目的　探讨盆腔淋巴结清扫术在Ⅰ期子宫内膜癌中的临床意义。方法　回顾性分析 1990年 1月～ 2 0 0 0年 12月 ,在我院住院治疗的Ⅰ期子宫内膜癌 112例 ,其中广泛或次广泛子宫切除术加盆腔淋巴结清扫术 6 6例 ,单纯广泛或次广泛子宫切除术 4 6例。结果　在 6 6例Ⅰ期子宫内膜癌中 ,发现 7例淋巴结转移 ,转移率为 10 6 %。Ⅰa期中无淋巴结转移 ;Ⅰb期转移率为 5 9% (2 34) ;Ⅰc期转移率为 2 5 % (5 2 0 )。Ⅰ期子宫内膜癌随着肌层浸润的加深其淋巴结转移率亦增加 ,P <0 0 5。而且特殊类型的子宫内膜癌其淋巴结转移率明显高于腺癌。但是行淋巴结清扫术与未行淋巴结清扫术的 5年生存率无差异。结论　Ⅰa期可以不做淋巴结清扫术 ,Ⅰc期和合并高危因素的Ⅰb期必须行盆腹腔淋巴结清扫术。且加强术前术中对肌层浸润程度的判断 ,以指导Ⅰ期亚分期的确定。淋巴结清扫术本身能否改善Ⅰ期患者的预后有待进一步研究。     

Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative

Objective

Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer.

Methods

We studied 86 937 postmenopausal women enrolled in the Women's Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade.

Results

During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade.

Conclusions

Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival.     

LRP16基因在子宫内膜样腺癌中的表达及意义

目的:探讨LRP16在子宫内膜样腺癌(EEC)中的表达及与临床病理的相关性。方法:用免疫组化法检测76例EEC患者癌组织标本中LRP16和雌激素受体α(ERα)的表达水平。结果:LRP16核阳性率为67.11%(51/76),LRP16浆阳性率为96.05%(73/76),浆核均阳性占64.47%(49/76);ERα阳性占51.32%(39/76),阴性占48.68(37/76)。ERα阴性患者中LRP16核阳性率(86.49%,32/37)明显高于ERα阳性患者(48.71%,19/39)(P<0.01),且LRP16在胞核中表达与EEC患者的手术病理分期无显著相关性(P>0.05)。在胞浆中分布的LRP16与ERα表达无关(P>0.05),但胞浆中的LRP16与EEC的手术病理分期呈明显的负相关(P<0.01),与组织学分级则无显著相关性(P>0.05)。在LRP16核浆均阳性的病例中,ERα阴性患者(81.08%,30/37)的比例明显高于ERα阳性患者(48.72%,19/39)(P<0.01);且LRP16在核浆中均有表达与EEC患者的手术病理分期及组织学分级无显著相关性(P>0·05)。在EEC肿瘤细胞中核、浆分布的LRP16着色强度呈负相关(P<0.05)。结论:LRP16在EEC细胞中均有表达,但其亚细胞分布与ERα状态密切相关,LRP16在胞浆中的表达可能提示预后良好。     

子宫内膜癌患者血清hsa-miR-155的表达及其临床意义

目的 探讨hsa-miR-155在子宫内膜癌患者血清中的表达及其临床意义.方法 选择2008年9月至2009年12月间解放军第一六九医院妇产科收治的44例子宫内膜癌患者,以同期12例健康志愿者作为对照,应用实时荧光定量PCR技术检测子宫内膜癌患者和健康志愿者血清hsa-miR-155的表达水平(以倍数表示),分析hsa-miR-155表达与子宫内膜癌临床病理指标间的关系.结果 相对于健康志愿者,子宫内膜癌患者血清hsa-miR-155的表达水平为(3.9±0.7)倍,两者比较,差异有统计学意义(P＜0.01).其中,高、中、低分化子宫内膜癌患者血清hsa-miR-155的表达水平分别为(3.7±0.6)、(3.9±0.6)、(3.7±0.6)倍,3者分别比较,差异均无统计学意义(P＞0.05);子宫内膜样腺癌与非子宫内膜样腺癌患者血清hsa-miR-155的表达水平分别为(3.8±0.6)、(3.9±0.6)倍,两者比较,差异无统计学意义(P＞0.05);Ⅰ～Ⅱ、Ⅲ～Ⅳ期子宫内膜癌患者血清hsa-miR-155的表达水平分别为(2.1±0.4)、(5.6±0.8)倍,两者比较,差异有统计学意义(P＜0.01);有、无盆腔淋巴结转移子宫内膜癌患者血清hsa-miR-155的表达水平分别为(5.5±0.5)、(1.9±0.2)倍,两者比较,差异有统计学意义(P＜0.01).结论 hsa-miR-155与子宫内膜癌的发生、转移密切相关,有可能成为判断子宫内膜癌疗效及预后的潜在生物学指标.     

Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression

Objective

This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE).

Methods

Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed.

Results

158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p = 0.0013) and stage 3-4 tumors (p = 0.0079), mean depth of myometrial invasion (p = 0.0019), lymphovascular space invasion (p = 0.0020), nodal metastases (p = 0.0157), and a lower incidence of Grade I (p = 0.0020) and stage 1A tumors (p = 0.0085). LOE had a significantly lower mean BMI (p = 0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40.

Conclusion

Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies.     

Mismatch repair protein expression in 1049 endometrial carcinomas,associations with body mass index,and other clinicopathologic variables

Objective

Links between obesity, with its attendant estrogen abnormalities, and the endometrial carcinoma (EC) DNA Mismatch Repair Protein (MMR) system have recently been proposed. We investigated relationships between body mass index (BMI) and clinicopathological correlates including MMR expression in a large single institution EC cohort.

Methods

Clinical and pathological databases from 2007 to 2012 were used to identify consecutive hysterectomy specimens with EC. Univariate and multivariate analyses were used to explore relationships between BMI, age, stage, tumor type and immunohistochemical results for MLH1, PMS2, MSH2 and MSH6.

Results

1049 EC were identified. Overall, BMI was higher amongst women with normal MMR (p = 0.002). However, when stratified by age and specific MMR, statistically significant differences localized exclusively to women < 50 years old with loss of MSH2 and/or MSH6 (p = 0.003 and p = 0.005 respectively). Higher BMI correlated with endometrioid FIGO 1 and 2 tumors (p < 0.001) and with stage 1a (p < 0.001). Conversely, MMR abnormalities did not show significant associations with stage (p = 0.302) or histologic grade (p = 0.097).

Conclusions

BMI showed statistically significant associations with MMR expression, tumor grade and stage amongst 1049 consecutive EC. Obesity correlates with lower grade and stage EC. A link between BMI and maintenance of the MMR system is not supported by our data because the only statistically significant association occurred in women < 50 years old with MSH2 and/or MSH6 abnormalities where Lynch syndrome related cases are expected to cluster.     

The effects of obesity and HER-2 polymorphisms as risk factors for endometrial cancer in Korean women

Objective  To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER-2 gene, body mass index (BMI) and the risk of endometrial cancer.
Design  Case–control study.
Setting  Medical centres in Korea.
Sample  DNA samples and medical histories were obtained from 125 endometrial cancer cases and 302 controls.
Methods  The genotypes evaluated in HER-2 at positions –423, –655, –776, –857, –1170, –1177, –1253 of the coding region and two SNPs located in an intron by SNP-IT assay using SNPstream Ultra–high throughput system.
Main outcome measures  Odd ratio for endometrial cancer associated with HER-2 polymorphisms and BMI.
Results  Cases had a significantly higher BMI than controls and the obese subjects had a 2.65-fold increased risk for endometrial cancer. However, HER-2 polymorphism was not associated significantly with the risk of endometrial cancer. Subjects with BMI ≥ 25 kg/m² who carried rs1801200 AA, rs1801200 GA/GG, rs1810132 CT/CC, rs2517951 CT/TT and rs1058808 CG/GG genotype had significantly increased risk of endometrial cancer than subjects with a normal BMI ( P for linear trend <0.05). However, the risk in the subjects with the variant allele for HER-2 genotypes did not differ significantly compared to those with homozygous wild-type allele within specific BMI subgroups.
Conclusions  Endometrial cancer risk increased significantly in proportion to BMI. However, HER-2 polymorphism did not affect significantly on the risk of endometrial cancer.     

PPARs在子宫内膜腺癌细胞中的表达及其激动剂对子宫内膜癌细胞生长抑制的影响

目的:探讨过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPARs)在子宫内膜癌细胞中的表达及PPARγ激动剂罗格列酮(Rosiglitazone)对体外培养人子宫内膜癌细胞系HHUA、KLE生长抑制和凋亡的影响。方法:RT-PCR检测PPARs在子宫内膜癌细胞中的表达;用MTT比色法分别检测罗格列酮作用于子宫内膜癌细胞HHUA、KLE不同时间后的细胞生长抑制率;流式细胞仪分析细胞周期分布; TUNEL检测细胞凋亡。结果:RT-PCR结果显示,两种子宫内膜癌细胞中均有PPARαPPARγmRNA表达,未见到PPARβmRNA表达;罗格列酮对人子宫内膜癌细胞的生长有抑制作用,呈时间剂量依赖性;流式细胞仪(FCM)检测结果显示盐酸罗格列酮作用于人子宫内膜癌细胞24h后,细胞周期被阻滞于G_1期;荧光显微镜,TUNEL检测显示, 200μmol/L罗格列酮作用子宫内膜癌细胞24h后出现典型的凋亡现象,细胞凋亡率为(18．3±1．9)%,与对照组(2．66±0．49)%相比差异有统计学意义(P＜0．05)。结论:罗格列酮对人子宫内膜癌细胞系的生长具有明显的抑制作用,促进细胞凋亡,其抗肿瘤作用机制可能是通过活化PPARγ途径诱导了细胞凋亡。