Ki-67、Her-2在乳腺浸润性导管癌中的表达与临床特征相关性研究

目的：探讨Ki－67、Her－2在乳腺浸润性导管癌中的表达情况及二者与临床特征的相关性。方法收集2012年1月至2014年9月军事医学科学院附属医院202例乳腺浸润性导管癌患者的临床及病理学资料,统计分析Ki－67、Her－2的表达与临床特征的相关性。结果在202例患者中,Ki－67阳性率为73．3％（148／202）,Her－2阳性率为19．3％（39／202）。 Ki－67的表达水平与组织学分级、激素受体（ER、PR）表达情况相关（P＜0．05）,与年龄大小、肿瘤直径、淋巴结转移均无关（P＞0．05）。 Her－2的表达与雌激素及孕激素受体表达相关（P＜0．05）,而与年龄大小、肿瘤直径、组织学分级、淋巴结转移均无关（ P＞0．05）。 Ki－67低表达、Her－2表达阴性时与雌激素及孕激素受体阳性表达呈正相关（P＜0．05）,与年龄大小、肿瘤直径、组织学分级、淋巴结转移均无关（P＞0．05）。 Ki－67表达水平与Her－2表达之间无相关性（P＜0．05）。结论 Ki－67高表达提示肿瘤组织学分级更高,分化程度更低,即肿瘤的恶性程度越高,越易转移;Ki－67高表达、Her－2阳性提示对内分泌治疗的敏感性低,治疗效果差;检测Ki－67、Her－2在乳腺浸润性导管癌中的表达对了解乳腺浸润性导管癌的恶性程度,指导患者个体化治疗及评估预后具有一定指导意义。     

Comparison of enhancement characteristics between invasive lobular carcinoma and invasive ductal carcinoma

Purpose:

To compare enhancement characteristics between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) on contrast enhanced MRI of the breast and to observe the magnitude of eventual differences as these may impair the diagnostic value of breast MRI in ILC.

Materials and Methods:

We performed an analysis of enhancement characteristics on biphasic breast MRI in a series of 136 patients (103 IDC, 33 ILC) using an in‐house developed application for pharmacokinetic modeling of contrast enhancement and a commercially available CAD application that evaluated the contrast‐enhancement versus time curve.

Results:

Pharmacokinetic analysis showed that the most enhancing voxels in IDC had significantly higher K^trans‐values than in ILC (P < 0.01). No difference in v_e‐values was noted between groups. Visual assessment of contrast‐enhancement versus time curves revealed wash‐out curves to be less common in ILC (48% versus 84%). However, when using the CAD‐application to assess the most malignant looking curve, the difference was blotted out (76% versus 86%).

Conclusion:

ILC enhances slower than IDC but peak enhancement is not significantly less. The use of a CAD‐application may help to determine the most malignant looking contrast‐enhancement versus time curve, and hence facilitates lesion classification. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

基于ADC和增强MRI的影像组学模型预测低级别胶质瘤TERT启动子突变状态

目的:探讨基于ADC和增强MRI的影像组学模型对低级别胶质瘤端粒酶逆转录酶基因（TERT）启动子突变状态的预测价值。方法:回顾性搜集109例经病理证实的低级别胶质瘤患者,所有患者术前均行MRI检查,在ADC和对比增强T₁WI（T₁CE）图像上选取病灶最大层面,沿肿瘤边缘勾画ROI,提取影像组学特征。采用三联法（Fisher, POE+ACC,MI）和最小绝对收缩选择算子（LASSO）进行特征筛选,然后行多因素logistic回归分析,构建影像组学预测模型。采用ROC曲线评估预测模型的诊断效能。结果:在ADC和T₁CE图像上分别提取279个影像组学特征,最终筛选出11个影像组学特征,分别建立ADC模型、T₁CE模型和联合分析（ADC+T1CE）模型共3个影像组学模型。联合分析模型的预测效能最佳,训练集中曲线下面积（AUC）为0.928（95%CI:0.859～0.996）,验证集中AUC为0.878（95%CI:0.758～0.997）。结论:基于ADC和增强MRI的影像组学模型能有效预测低级别胶质瘤...     

上腰椎与下腰椎动态增强MRI(DCE MRI)灌注参数的差异

研究年龄、性别、腰椎节段对正常腰椎骨髓动态增强MRI(DCE MRI)灌注参数的影响。对67例下腰痛或坐骨神经痛病人进行了腰椎DCEMRI检查。动态增强影像     

Differences in perfusion parameters between upper and lower lumbar vertebral segments with dynamic contrast-enhanced MRI (DCE MRI)

To investigate the influence of age, sex and spinal level on perfusion parameters of normal lumbar bone marrow with dynamic contrast-enhanced MRI (DCE MRI). Sixty-seven subjects referred for evaluation of low back pain or sciatica underwent DCE MRI of the lumbar spine. After subtraction of dynamic images, a region of interest (ROI) was placed on each lumbar vertebral body of all subjects, and time intensity curves were generated. Consequently, perfusion parameters were calculated. Statistical analysis was performed to search for perfusion differences among lumbar vertebrae and in relation to age and sex. Upper (L1, L2) and lower (L3, L4, L5) vertebrae showed significant differences in perfusion parameters (p<0.05). Vertebrae of subjects younger than 50 years showed significantly higher perfusion compared to vertebrae of older ones (p<0.05). Vertebrae of females demonstrated significantly increased perfusion compared to those of males of corresponding age (p<0.05). All perfusion parameters, except for washout (WOUT), showed a mild linear correlation with age. Time to maximum slope (TMSP) and time to peak (TTPK) showed the same correlation with sex (0.22<r<0.32, p<0.05). Our results indicate increased perfusion of the upper compared to the lower lumbar spine, of younger compared to older subjects and of females compared to males.     

Diffusion-weighted MRI provides additional value to conventional dynamic contrast-enhanced MRI for detection of hepatocellular carcinoma

The purpose of this study was to evaluate the accuracy of diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating HCC from benign cirrhotic lesions compared with conventional dynamic contrast-enhanced MRI. Fifty-five patients with cirrhosis underwent conventional and DW-MRI at 1.5 Tesla. Signal intensity ratios (SI_ratio) of solid liver lesions to adjacent hepatic parenchyma were measured for b0, b100, b600 and b1000, and the apparent diffusion coefficients (ADC) were calculated. In 27 patients, imaging results were compared to histopathology, and in 28 patients, to imaging follow-up. Based on predetermined thresholds, sensitivity and specificity of DW-MRI and conventional MRI were compared. SI_ratio was significantly different between malignant and benign lesions at all b-values (P?<?0.0001). No significant difference in ADC was seen (P?=?0.47). For detection of malignant lesions, DW-MRI with b600-SI_ratio yielded a sensitivity of 95.2% compared to 80.6% for conventional MRI (P?=?0.023) and a specificity of 82.7% compared to 65.4% (P?=?0.064). The improved accuracy was most beneficial for differentiating malignant lesions smaller than 2 cm. DW-MRI with b600-SI_ratio improved the detection of small HCC and the differentiation of pseudotumoral lesions compared with conventional MRI.     

子宫内膜癌MRI征象与血管内皮生长因子、Ki-67表达的相关性研究

目的评价MRI征象结合血管内皮生长因子(VEGF)和增殖细胞核抗原(Ki-67)的表达在诊断子宫内膜癌及反映肿瘤分子生物学特性中的价值。资料与方法回顾性分析经病理证实为子宫内膜癌的56例患者,术前1周行MRI扫描,以SP染色法检测56例子宫内膜癌石蜡切片中VEGF、Ki-67的表达情况,并以10例正常子宫内膜作为对照,评价MRI诊断子宫内膜癌的灵敏度,分析MRI分期与VEGF、Ki-67表达的相关性。结果 56例中MRI诊断为子宫内膜癌53例,诊断灵敏度为94.6%,其中Ⅰ期34例,诊断符合25例,诊断准确率为73.5%;Ⅱ期17例,诊断符合15例,诊断准确率为88.2%;Ⅲ期5例,诊断符合5例,诊断准确率为100%。VEGF表达指数:正常内膜2.75±1.04,Ⅰ期12.99±3.48,Ⅱ期20.12±5.08,Ⅲ期37.13±7.23;Ki-67的表达指数:正常内膜6.74±2.67,Ⅰ期18.32±5.28,Ⅱ期36.41±8.06,Ⅲ期48.75±9.04。VEGF、Ki-67的表达与MRI分期呈正相关(r=0.772、0.823,P=0.001),表达指数随分期增加而增高。结论 MRI成像对子宫内膜癌术前分期具有较好的诊断价值,结合癌组织VEGF、Ki-67的表达,有利于临床治疗方案的选择。     

基于T2WI和增强MRI影像组学列线图预测宫颈鳞癌淋巴脉管间隙浸润

目的:探讨基于T₂WI和增强MRI影像组学列线图对宫颈鳞癌淋巴脉管间隙浸润(LVSI)的预测价值。方法:将92例经术后病理证实的宫颈鳞癌患者纳入研究,并按7:3的比例随机分为训练集(66例)和验证集(26例)。所有患者术前行MRI检查,在横轴面T₂WI和对比增强T₁WI(T1CE)上选取病灶最大层面沿肿瘤边缘勾画ROI,应用AK软件提取影像组学特征。采用mRMR和LASSO回归分析对提取的纹理特征进行初步筛选,然后进行多因素logistic回归分析,构建影像组学模型。使用单因素logistic回归分析筛选临床病理危险因素,并使用多因素logistic回归结合影像组学评分(Radscore)构建影像组学列线图。应用ROC曲线评估影像组学模型、临床病理危险因素模型和影像组学列线图模型的预测能力,并应用决策曲线分析评估影像组学列线图的临床应用价值。结果:在T₂WI和T1CE图像上分别提取病灶的396个影像组学特征,最终筛选出14个具有最大诊断效能的纹理特征。使用多因素logistic回归构建包含FIGO分期、分化程度和Radscore的影像组学列线图。影像组学列线图的预测效能优于临床病理危险因素模型(训练集中,AUC:0.96 vs.0.70;Delong检验:Z=4.04,P=5.415e-05;验证集中,AUC:0.87 vs.0.71;delong检验:Z=1.24,P=0.02)。决策曲线分析显示风险阈值为0.01~1.00时使用影像组学列线图对预测宫颈鳞癌LVSI情况的临床应用价值较大。结论:基于双序列MRI构建的影像组学列线图对宫颈鳞癌LVSI情况有较好的预测能力,可作为一种术前评估的无创性影像学生物标志。     

Differentiation between ductal carcinoma in situ and mastopathy using dynamic contrast-enhanced magnetic resonance imaging and a model of contrast enhancement

The purpose of this study was to retrospectively evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between ductal carcinoma in situ (DCIS) and mastopathy by analyzing their time-intensity curves (TICs) using the two-compartment pharmacokinetic model with an assumption of instantaneous injection of contrast medium (TCPM).After the pre-contrast MRI was performed using a 1.5 T MRI system, DCE-MRI was performed four times after the intravenous administration of contrast medium. We set the volumes of interest (VOIs) on the tumor and normal mammary gland, and obtained the TICs in these VOIs. We calculated the following parameters by fitting these TICs to the equation derived from TCPM; the initial slope of the TIC (Slope_ini), the area under the TIC (AUC), the time to peak enhancement (TTP) and the peak enhancement (PeakE). We calculated these parameters in both the lesion and normal mammary gland and the ratios of the parameters in the lesion to those in the normal gland (rSlope_ini, rAUC, rTTP and rPeakE).There were significant differences in Slope_ini (P = 0.009), PeakE (P = 0.019), rSlope_ini (P = 0.010), and rTTP (P = 0.005) between DCIS and mastopathy. The areas under the receiver operating characteristic curve for Slope_ini, PeakE, rSlope_ini, and rTTP were 0.67 ± 0.06 (P = 0.009), 0.65 ± 0.06 (P = 0.019), 0.67 ± 0.06 (P = 0.01), and 0.68 ± 0.06 (P = 0.005), respectively.In conclusion, our results suggest that analysis of TICs obtained by DCE-MRI using TCPM appears to be useful for differentiating between DCIS and mastopathy.     

基于动态对比增强MRI的肿瘤血流动力学及形态学特征预测乳腺癌术后复发时间的价值

目的探讨乳腺癌患者术前经常规动态对比增强MRI(DCE-MRI)扫描后获得的肿瘤血流动力学及形态学特征预测术后复发时间的价值。方法回顾性分析2012年11月至2014年12月辽宁省肿瘤医院术后复发的乳腺癌患者58例,依据复发时间分为早期复发(术后≤2年)组33例,晚期复发(术后>2年)组25例。所有患者均在术前行常规DCE-MRI扫描,通过计算机提取肿瘤三维容积内的血流动力学特征及在每一个期相下的肿瘤形态学特征及纹理特征。早期复发组和晚期复发组患者间计数资料和计量资料的比较分别采用Fisher精确概率法和Mann-Whitney U检验,绘制受试者操作特征(ROC)曲线,应用多元logistic回归计算特征联合预测早期复发与晚期复发的诊断效能。应用Kaplan-Meier法分析生存预后,并用Log-Rank检验比较各组生存曲线的差异。结果早期复发组和晚期复发组患者背景实质强化、病灶边缘、病灶内部强化特征、病灶形态、时间信号曲线类型和全乳血管增加程度的差异均无统计学意义(P均>0.05);2组患者的对比剂最大浓度值(Max Conc)、时间信号曲线下面积(AUC)及时间信号曲线最大斜率值(Max Slope)值差异有统计学意义(P<0.05)。对比分析8期DCE-MRI影像组学特征参数,第3期形态特征参数球度(sphericity)在早期复发与晚期复发组间差异有统计学意义(P=0.03)。AUC、Max Conc、Max Slope和第3期形态特征参数球度预测早期与晚期复发的ROC曲线下面积分别为0.664、0.659、0.684、0.670,上述4个参数联合预测的ROC曲线下面积为0.765,特异度为63.6%,灵敏度为84.0%,预测效能高于单变量。58例患者随访时间17~64个月,中位随访时间47个月。早期复发组的无进展生存和总生存均明显低于晚期复发组,差异有统计学意义(P<0.05)。结论基于术前无创性常规DCE-MRI获取的肿瘤血流动力学特征联合形态学特征预测乳腺癌患者的术后复发时间有一定的价值。     

Measurement of pharmacokinetic parameters in histologically graded invasive breast tumours using dynamic contrast-enhanced MRI

Dynamic contrast-enhanced MRI (DCE-MRI) has demonstrated high sensitivity for detection of breast cancer. Analysis of correlation between quantitative DCE-MRI findings and prognostic factors (such as histological tumour grade) is important for defining the role of this technique in the diagnosis of breast cancer as well as the monitoring of neoadjuvant therapies. This paper presents a practical clinical application of a quantitative pharmacokinetic model to study histologically confirmed and graded invasive human breast tumours. The hypothesis is that, given a documented difference in capillary permeability between benign and malignant breast tumours, a relationship between permeability-related DCE-MRI parameters and tumour aggressiveness persists within invasive breast carcinomas. In addition, it was hypothesized that pharmacokinetic parameters may demonstrate stronger correlation with prognostic factors than the more conventional black-box techniques, so a comparison was undertaken. Significant correlations were found between pharmacokinetic and black-box parameters in 59 invasive breast carcinomas. However, statistically significant variation with tumour grade was demonstrated in only two permeability-related pharmacokinetic parameters: k(ep) (p<0.05) and K(trans) (p<0.05), using one-way analysis of variance. Parameters k(ep) and K(trans) were significantly higher in Grade 3 tumours than in low-grade tumours. None of the measured DCE-MRI parameters varied significantly between Grade 1 and Grade 2 tumours. Measurement of k(ep) and K(trans) might therefore be used to monitor the effectiveness of neoadjuvant treatment of high-grade invasive breast carcinomas, but is unlikely to demonstrate remission in low-grade tumours.     

采用动态对比增强CT评估肿瘤血供的现状及指南

摘要动态对比增强CT(DCE-CT)通过在静脉注射碘对比剂后快速采集一系列图像,并分析对比剂在血管和组织里的时间密度变化来评估肿瘤血供。DCE-CT分析的商用软件能够对一系列证实的生理参数逐像素计算并生成参数图。临床研究支持采用DCE-CT参数反映肿瘤血管生成的生理和分子过程。DCE-CT在很多肿瘤早期治疗试验中被用于提供药物作用的生物学标志。由于DCE-CT应用广泛,且价格低廉,已经成为当前肿瘤疗效评估的影像学手段之一。     

Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points ? DCE-CT can robustly assess tumour vascular support ? DCE-CT has reached technical maturity for use in therapeutic trials in oncology ? This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.     

Ki-67和p53与肾癌的相关性研究

目的探讨Ki-67和p53蛋白在肾癌中的表达和临床意义。方法应用免疫组化方法对66例肾癌组织进行Ki-67和p53蛋白检测。结果在肾癌组织中Ki-67和p53蛋白表达阳性率分别为62.1%和39.4%。Ki-67表达与肾细胞癌分级、分期相关(P<0.05),与肾癌的病理类型无关(P>0.05)。p53表达与肾癌的病理类型、分级、分期无关(P>0.05)。结论 Ki-67表达水平随着肾癌组织的病理分级和临床分期的增高而增高,与肿瘤的生物学行为有一定关系。而p53表达在肾癌生物学行为不具有重要意义。