子宫颈癌IVIM与DCE-MRI灌注相关性研究

目的分析体素内不相干运动(introvoxel incoherent motion,IVIM)与磁共振动态增强扫描(dynamic contrast enhanced MRI,DCE-MRI)两种模型评估子宫颈癌血流灌注参数的相关性,并探讨两种模型参数对不同病理类型子宫颈癌的诊断价值。材料与方法搜集我院2016年4月至2017年6月初诊子宫颈癌53例,所有患者于治疗前行MRI检查,包括IVIM及DCE-MRI序列,测量IVIM的灌注参数D*值、f值,计算两者的乘积f D*值,测量DCE-MRI的参数K~(trans),K_(ep)、Ve值。采用Spearman法分析全部子宫颈癌组、子宫颈鳞癌组及子宫颈腺癌组各参数的相关性。采用独立样本t或t'检验比较各参数在子宫颈鳞癌与腺癌组的差异,并进行ROC曲线分析。结果全部子宫颈癌组,D*及f D*均与DCE-MRI各参数呈轻度至中度正相关(r值:0.357~0.672),而f与DCE-MRI各参数均无相关性。D*与Ktrans在子宫颈腺癌组呈高度正相关性(r=0.900),而在鳞癌组呈轻度至中度正相关(r=0.669)。宫颈腺癌的f、K~(trans)、K_(ep)值均高于宫颈鳞癌(P值:0.002~0.013),ROC曲线分析曲线下面积为0.788、0.749及0.722,以f值0.29为临界值,诊断子宫颈腺癌的敏感度、特异度及准确率分别为63.64%,92.86%及86.79%。结论不同病理类型子宫颈癌的IVIM及DCE-MRI模型灌注参数均呈正相关,f、Ktrans及Kep值有助于子宫颈鳞癌和腺癌的鉴别。     

Staging of uterine cervical carcinoma: whole-body diffusion-weighted magnetic resonance imaging

Purpose  

To evaluate the clinical value of magnetic resonance whole-body diffusion-weighted imaging (WB-DWI) in the staging of uterine cervical carcinoma.     

HER2 codon 655 polymorphism is associated with advanced uterine cervical carcinoma

Objectives:It has been suggested that overexpression of HER2 in advanced cervical tumors can be considered an independent predictor of poor patient outcome.Design and methods:Employing PCR-RFLPs, we examined the distribution of HER2 Ile655Val (rs 1136201) genotypes and alleles in patients with advanced cervical cancer (n = 109) and controls (n = 220).Results:Odds ratio (OR) for patients with advanced cervical cancer with the HER2 Val/Val homozygous or Val/Ile heterozygous state was 1.778 (95% CI = 1.117–2.830, p = 0.0176). We also observed an association of the HER2 Val/Val genotype with advanced cervical cancer in the patient group OR = 3.706 (95% CI = 1.061–12.950, p = 0.0459). However, we did not find a significant association between the distribution of genotypes or alleles and cancer characteristics for the HER2 Ile655Val polymorphism.Conclusions:Our results indicate that the HER2 655Val variant may be associated with the incidence of advanced cervical cancer.     

经子宫动脉化疗栓塞术对宫颈癌VEGF、MVD的影响

目的：通过检测宫颈癌血管内皮生长因子（VEGF）及微血管密度（MVD）在经子宫动脉化疗栓塞术前后的表达，观察经子宫动脉化疗栓塞术对宫颈癌VEGF和MVD的影响。方法：采用免疫组织化学法，分别对42例宫颈癌患者经子宫动脉化疗栓塞术前后的肿瘤组织测定MVD及VEGF的表达。结果：本组患者经子宫动脉化疗栓塞术后VEGF阳性表达率自术前的67％（28／42）降至35％（15／42），同时其MVD计数明显降低（P〈0．05）。结论：经子宫动脉化疗栓塞术能降低宫颈癌组织VEGF的表达，减少MVD计数，提示此方法可能抑制宫颈癌的生长，减少术后转移。     

宫颈癌组织P16基因突变分析

探讨Ｐ１６基因突变在宫颈癌发生中的作用及基突变的机制，利用点突变检测仪，水平和垂直板电泳对Ｐ１６基因的外显子１，外显子２的ＰＣＲ扩增产物作缺失和点突变发析，结果在２９例临床宫颈癌标本中的有８例发生缺失突变，４例发生点突变，突变率为４１％，其中１例外显子１为不完全缺失突变即有低于３４３ｂｐ的扩增带，Ｐ１６基因的发突变原因是因为其含有“ＣＧ”ＤＮＡ重复顺序，易发生ＤＮＡ重组及易位和重排。     

多序列MRI纹理分析预测宫颈癌新辅助化学治疗疗效

目的 观察不同序列MRI纹理特征分析预测宫颈癌新辅助化学治疗（NACT）疗效的价值。方法 回顾性分析32例接受NACT的宫颈癌患者，于NACT开始前及结束后各行1次盆腔MR，根据实体瘤疗效评价标准（RECIST）将患者分为有效组（完全缓解和部分缓解）及无效组（疾病稳定和疾病进展）。于治疗前MR T2WI、DWI及增强图像上分别勾画ROI，获得纹理参数，每组图像共采集106个纹理特征，比较2组参数差异。对每组选取诊断效能较高且相关性小的纹理特征参数进行Logistic回归分析，获得综合参数；绘制受试者工作特征（ROC）曲线，得到各序列单因素及回归模型的预测价值，并对各序列进行比较。结果 治疗前T2WI、DWI和增强图像纹理特征中，分别有22、13和36个组间差异存在统计学意义（P均<0.05）；T2WI、DWI和增强图像单个纹理特征预测宫颈癌NACT效果的ROC曲线下面积（AUC）分别为0.609~0.839、0.745~0.813及0.552~0.786，综合模型预测疗效的AUC分别为0.839、0.885及0.766。结论 不同序列MRI纹理分析预测NACT对于宫颈癌的疗效具有较高价值，以DWI最佳。     

CyclinD1和P27在宫颈鳞癌中的表达及临床意义

目的研究CyclinD1和P27蛋白在宫颈鳞状细胞癌发生、发展中的作用及其与宫颈鳞癌临床病理特征的关系。方法应用SP免疫组化法检测40例宫颈鳞癌,25例宫颈不典型增生组织中CyclinD1和P27蛋白的表达,取正常宫颈组织10例作为对照。结果CyclinD1在宫颈鳞癌中呈高表达,P27在宫颈鳞癌中呈低表达,与对照组均有组间差异(P<0.05)。在鳞癌组中,CyclinD1与P27的异常表达与组织学分级,临床分期和淋巴结转移有关(P<0.05),且二者在宫颈鳞癌中的表达呈负相关(rs=-0.397)。结论CyclinD1癌基因和P27抑癌基因突变协同作用于鳞状细胞癌的发生与发展。二者的检测可作为评价宫颈鳞状细胞癌恶性程度和判断预后的重要指标。     

Survivin在宫颈鳞癌中的表达及临床意义

目的 探讨宫颈鳞癌组织中survivin基因表达的特征及临床意义。方法 采用免疫组织化学方法（PV法）检测54例宫颈鳞癌，16例正常官颈组织中Survivin基因的表达，并分析其临床病理特征。结果 Survivin在正常宫颈组织中不表达，在官颈鳞癌组织中阳性表达率与年龄、临床分期及淋巴结转移有关。结论 Survivin基因在官颈鳞癌组织中的稳定表达。预示肿瘤有较高的侵袭性和不良预后，可能成为有效的预测官颈鳞癌侵袭性的监测指标及判断预后的指标，对指导临床治疗具有重要意义。     

宫颈脱落细胞RASSF1A基因甲基化在宫颈癌中的临床意义

目的研究宫颈脱落细胞RAS相关区域家族1A(RASSF1A)基因启动子甲基化在宫颈癌中的临床意义。方法应用甲基化特异性聚合酶链反应检测宫颈癌患者和健康女性宫颈脱落细胞RASSF1A基因启动子甲基化,分析与病理因素间的关系。结果宫颈癌患者宫颈脱落细胞RASSF1A基因启动子甲基化率为64.0%,高于健康女性的1.3%(P<0.05)。宫颈脱落细胞RASSF1A基因启动子甲基化率在宫颈癌不同组织学分级、肿瘤最大径、淋巴结转移、器官转移、Figo分期患者间的差异具有统计学意义(P<0.05)。结论宫颈脱落细胞RASSF1A基因启动子甲基化与宫颈癌病理因素密切相关,可作为宫颈癌病情判断和预后评估的标志物。     

KAI1转移抑制基因在宫颈鳞癌中的表达及其临床意义

目的　检测宫颈鳞癌中KAI1在mRNA水平的表达,探讨其与宫颈癌侵袭转移的关系。方法　采用逆转录-多聚酶链反应(RT-PCR)技术检测新鲜组织KAI1 mRNA的表达,宫颈鳞癌组52例,正常对照组21例。结果　(1) KAI1 mRNA 在正常宫颈上皮及宫颈癌组织中阳性率分别为100%,61.53%,差异具有显著意义(P<0.05)。(2) 在高、中、低分化宫颈癌组织中KAI1 mRNA阳性率分别为76.47%、68.18%和30.70%,三组间差异有极显著意义(P<0.01)。(3) KAI1 mRNA在≤ⅡA、ⅡB、Ⅲ/Ⅳ期宫颈癌组织中表达阳性率分别为68.00%、55.56%和55.56%,阳性率在各期间差异无显著意义(P>0.05)。(4) KAI1 在无淋巴转移组的阳性率(27/34,79.41%)明显高于有淋巴转移组(5/18,27.78%),差异有显著意义(P<0.05)。结论　KAI1 mRNA在宫颈鳞癌组织中表达减少,其表达与细胞分化及转移有关,提示KAI1可能参与了宫颈癌的发生发展,可能在一定程度上具有预测宫颈癌侵袭转移的潜能。     

Comparison of MR imaging features of uterine neuroendocrine carcinoma and uterine malignant lymphoma

Purpose

We retrospectively investigated the characteristic magnetic resonance (MR) imaging findings of uterine neuroendocrine carcinoma (UNEC) compared to those of uterine malignant lymphoma (UML).

Methods

Nine consecutive female patients with UNEC and 5 female patients with UML participated in this study. MR imaging features were evaluated retrospectively.

Results

On MR imaging, seven of 9 UNEC lesions and no UML lesions showed an exophytic growth pattern. All 9 UNEC lesions and no UML lesions showed a growth pattern along the surface of the endocervix or endometrium. Only 1 UNEC lesion and all 5 UML lesions showed diffuse enlargement of the uterus. No UNEC lesions and all 5 UML lesions showed a multinodular shape. These findings showed significant differences between lesions. Findings for margin, endophytic growth pattern, signal intensity, and homogeneity on T2-weighted and T1-weighted imaging did not differ significantly between lesion types. Apparent diffusion coefficient was significantly lower for UML lesions than for UNEC lesions, but was quite low for both types. Local invasion to surrounding tissues was more frequent in UML lesions than in UNEC lesions. There was no significant difference in the frequency of lymphadenopathy between two entities.

Conclusions

UNEC lesions tended to show an exophytic growth pattern and growth along the surface of the endocervix or endometrium, even when diffuse enlargement of the uterus was present, while all UML lesions showed a multinodular shape and diffuse enlargement of the uterus without thickening of the cervical epithelium and endometrium.

     

磁共振扩散峰度成像评价宫颈癌放疗后变化的小鼠实验研究

目的评价宫颈癌小鼠模型放疗前后的磁共振扩散峰度成像参数变化情况。材料与方法建立皮下种植成瘤的宫颈癌小鼠模型11只,在一侧腹股沟区及对侧腋下分别成瘤,对腹股沟区肿瘤行一次性大剂量放疗照射,腋下肿瘤作为未经放疗的对照组。对两部位肿瘤放疗前及放疗后1周左右行常规MR T2WI及磁共振扩散峰度成像(diffusion kurtosis imaging,DKI)成像,感兴趣区选取肿瘤全层面,计算表观扩散系数(apparent diffusion coefficient,ADC)值、平均扩散率(mean diffusivity,MD)、平均峰度值(mean kurtosis,MK)的平均值(av)及中位值(m)。对比放疗前各参数值的相关性(Pearson相关性检验),以及放疗前后在放疗组和对照组的变化差异(配对t检验)。结果放疗前的ADC值与MK之间存在强负相关性,ADC值与MD之间存在强正相关性(相关系数均大于0.7)。与放疗前相比,腹股沟组肿瘤放疗后的ADC值明显升高(ADCav分别为0.571±0.063×1 0~(-3) mm~2/s和0.6 1 1±0.0 5 5×1 0~(-3) mm~2/s,P=0.0 1 5;A D C m分别为0.543±0.052×10~(-3) mm~2/s和0.587±0.041×10~(-3) mm~2/s,P=0.013),MK值明显降低(MKav分别为1.14±0.12和1.02±0.10,P=0.003;MKm分别为1.13±0.10和1.14±0.10,P=0.003),而MD值的变化无统计学差异(MDav分别为0.856±0.105×10~(-3) mm~2/s和0.885±0.071×10~(-3) mm~2/s,P0.05;MDm分别为0.843±0.113×10~(-3) mm~2/s和0.878±0.081×10~(-3) mm~2/s,P0.05)。MK平均值变化幅度约9.4%,ADC平均值变化幅度约7.5%。对照组肿瘤前后两次ADC值、MD值和MK值均无统计学显著性差异(P0.05)。结论宫颈癌放疗后会引起ADC值的升高和MK的降低,其中MK的变化幅度相对稍高,提示扩散峰度成像用于放疗评价的可行性。     

Lymphoepithelioma-like carcinoma of the uterine cervix

We describe two rare cervical tumors having morphologic features closely resembling those of the nasopharyngeal lymphoepithelioma. This entity has historically been classified as a subtype of squamous cell carcinoma, but after reviewing the literature and the two cases presented here, we propose that this tumor is a distinct carcinoma of the cervix that differs from squamous cell carcinoma in that it carries a more favorable prognosis, typically affects a younger population of women, is more prevalent in noncaucasian populations (especially those of Asian descent), and lacks a clearly defined association with infection due to human papilloma virus (HPV).     

宫颈癌超声造影的诊断价值及与Egr-1基因表达的相关性

目的探讨宫颈癌患者的超声造影特征及其与Egr-1基因表达的相关性。方法分析40例病理确诊为宫颈癌患者的经腹超声造影特征,观察肿瘤的形态结构、血流信号分布及多普勒血流特征,对术后的肿瘤组织应用QRTPCR检测Egr-1基因的表达,分析超声造影表现与Egr-1基因表达之间的相关性。结果肿瘤组织的峰值强度(PI)为(75.71±2.13)显著高于正常组织(58.12±1.92),差异具有统计学意义(P0.001)。肿瘤组织的病灶达峰时间(TTP)为(32.43±1.76)s显著短于正常组织(40.41±2.24)s,差异具有统计学意义(P=0.003);Egr-1基因在宫颈癌组织标本中的表达明显低于癌旁组织,差异具有统计学意义(P0.001);Egr-1基因的表达与宫颈有无肿物,肿块的大小(≤4 cm)、淋巴结转移及病理分级相关(P均0.05);宫颈癌造影增强强度与Egr-1表达相关,与肿瘤大小、淋巴结转移及病理分级无明显相关关系(P0.05);非均匀性增强在Egr-1低表达患者中的比率明显高于Egr-1高表达者,差异具有统计学意义(P0.05)。结论宫颈癌超声造影特征可显示其与Egr-1基因表达的相关性,有助于无创性评估宫颈癌的预后评估。     

宫颈癌中FHIT基因CpG岛甲基化检测意义

目的探讨宫颈癌患者中脆性组氨酸三联体基因（fragile histidine triad,FHIT）CpG岛甲基化状态及其在宫颈癌诊断中价值。方法采用甲基化特异性PCR技术检测45例宫颈癌组织及血浆中、10例正常宫颈组织中FHIT基因CpG岛甲基化状态。结果 FHIT基因在宫颈癌组织及血浆中CpG岛甲基化率分别为55.6%和35.6%,正常宫颈组织中未检测出FHIT基因CpG岛甲基化,宫颈癌组织及血浆中CpG岛甲基化改变与正常对照比较差异有统计学意义（P〈0.05）;癌组织中FHIT基因甲基化发生率与年龄、病理分级、临床分期间差异无统计学意义（P〉0.05）。结论 FHIT基因CpG岛甲基化检测在宫颈癌早期诊断中有一定价值。     

Genetic variants of microsomal metabolism and susceptibility to hydrocarbon-associated glomerulonephritis

Hydrocarbon (HC) exposure can play a role in the development of chronic glomerulonephritis (GN). Interindividual variations in various metabolizing enzymes may influence HC biotransformation, and hence susceptibility to HC-associated GN. We evaluated the role of human genotypic polymorphism in HC-associated GN, in 41 patients (30 male, 11 female) with primary GN (17 diffuse mesangial proliferative GN, 12 focal segmental GN, 11 membranous GN, one membranoproliferative GN) and 60 (46 male, 14 female) healthy controls. Genotypic polymorphisms of (CYP) P450 2D6 (CYP2D6), glutathione S-transferases mu (GSTM1) and theta (GSTT1) and N-acetyltransferase (NAT-2) were determined using polymerase chain reaction analysis of white-blood-cell DNA. HC exposure scores were determined using a validated questionnaire, and were significantly elevated in GN patients compared to controls. While no significant differences in the various genotypic frequencies were observed in the GN group overall, compared to controls, there was a significant increase in GSTM1 null (n = 10) to GSTM1 wild type (n = 1), and NAT fast (n = 10) to slow (n = 1) acetylators, in the membranous GN group compared to controls (p < 0.05). These results suggest a possible role for GSTM1 null and NAT fast acetylator in the development of HC- associated membranous GN.      

p53基因异常与胃癌发生发展的关系

p53基因在恶性肿瘤发生发展中的作用已被许多研究证实，胃癌发生过程中伴有p53基因突变。为探讨p53基因异常与胃癌发生发展的关系，应用免疫组化技术检测58例胃癌和相应癌旁组织中P53蛋白表达．聚合酶链反应-单链构象多态分析(PCR—SSCP)结合DNA测序检测p53基因exon5-8突变情况。