全数字化X线摄影联合MR 动态增强检查诊断早期乳腺癌的 临床价值研究

摘要目的：分析早期乳腺癌的全数字X 线摄影与MRI影像学表现,评价全数字X 线摄影联合MRI 检查在早期乳腺癌诊断中的 临床价值。方法：回顾性分析2009 年10 月至2012 年5月在我院经穿刺或手术病理证实为早期乳腺癌的42例患者的临床资料, 术前均行数字X线及动态增强MR 检查,比较两种方法单独使用和联合使用的诊断乳腺癌的准确率。结果：全数字化X 线摄片 诊断早期乳腺癌的准确率为69.0%(29/42),动态增强MR 检查为95.2%(40/42),两者比较差异有统计学意义(P<0.05);两者联合使 用诊断早期乳腺癌的准确率为97.6%(41/42)。结论：动态增强MR 检查对早期乳腺癌的诊断价值明显优于全数字X线摄影,但后 者对微小钙化显示较好,两者联合可提高诊断正确率,尤其对多腺体型和致密型乳腺的早期乳腺癌的检出具有重要的价值。     

全数字化X线摄影联合MR动态增强检查诊断早期乳腺癌的临床价值研究

目的：分析早期乳腺癌的全数字X线摄影与MRI影像学表现,评价全数字X线摄影联合MRI检查在早期乳腺癌诊断中的临床价值。方法：回顾性分析2009年10月至2012年5月在我院经穿刺或手术病理证实为早期乳腺癌的42例患者的临床资料,术前均行数字X线及动态增强MR检查,比较两种方法单独使用和联合使用的诊断乳腺癌的准确率。结果：全数字化X线摄片诊断早期乳腺癌的准确率为69．0％（29／42）,动态增强MR检查为95．2％（40／42）,两者比较差异有统计学意义（P〈0．05）;两者联合使用诊断早期乳腺癌的准确率为97．6％（41／42）。结论：动态增强MR检查对早期乳腺癌的诊断价值明显优于全数字X线摄影,但后者对微小钙化显示较好,两者联合可提高诊断正确率,尤其对多腺体型和致密型乳腺的早期乳腺癌的检出具有重要的价值。     

乳腺癌钼靶X线检查的漏诊及误诊分析

目的:分析乳腺癌X线检查的误诊及漏诊情况。方法:选择2013年5月至2015年5月在我院的经乳腺X线和病理检查证实的乳腺肿瘤患者135例为研究对象,比较X线检查结果与病理诊断结果的误诊率及漏诊率,并分析导致误诊及漏诊的因素。结果:135例患者中,术后病理证实为恶性肿瘤63例(46.67%),良性肿瘤72例(53.33%)。63例乳腺恶性肿瘤中,X线误诊为良性5例,误诊率为7.93%。其中1例误诊为乳腺增生,2例误诊为乳腺炎症,1例误诊为术后疤痕挛缩,1例误诊为纤维腺瘤;X线表现为肿块形态呈圆形或类圆形边缘光滑2例,肿块周围出现透亮区1例,乳腺结构扭曲1例。72例良性肿瘤中,X线误诊为恶性7例,误诊率为9.72%。其中4例为乳腺增生,2例为乳腺炎,1例为乳腺纤维瘤,1例为乳腺筋膜炎;X线表现为密度较高而边缘不清的肿块影1例,边缘似有毛刺征1例,伴有钙化、模糊无定型呈散在分布1例,部分边缘有突起或后缘凹凸不平1例,片状影2例(1例密度较高,1例密度较均匀);肿块伴乳晕增厚、乳头内陷1例。结论:乳腺X线检查的准确性受直接征象和间接征象的影响。因此,临床实践中可联合运用乳腺X线检查和乳腺超声或MRI检查,从而提高乳腺肿块诊断的准确率。     

Differentiation of Breast Cancer from Fibroadenoma with Dual-Echo Dynamic Contrast-Enhanced MRI

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) of the breast is a routinely used imaging method which is highly sensitive for detecting breast malignancy. Specificity, though, remains suboptimal. Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI), an alternative dynamic contrast imaging technique, evaluates perfusion-related parameters unique from DCE MRI. Previous work has shown that the combination of DSC MRI with DCE MRI can improve diagnostic specificity, though an additional administration of intravenous contrast is required. Dual-echo MRI can measure both T₁W DCE MRI and T₂*W DSC MRI parameters with a single contrast bolus, but has not been previously implemented in breast imaging. We have developed a dual-echo gradient-echo sequence to perform such simultaneous measurements in the breast, and use it to calculate the semi-quantitative T₁W and T₂*W related parameters such as peak enhancement ratio, time of maximal enhancement, regional blood flow, and regional blood volume in 20 malignant lesions and 10 benign fibroadenomas in 38 patients. Imaging parameters were compared to surgical or biopsy obtained tissue samples. Receiver operating characteristic (ROC) curves and area under the ROC curves were calculated for each parameter and combination of parameters. The time of maximal enhancement derived from DCE MRI had a 90% sensitivity and 69% specificity for predicting malignancy. When combined with DSC MRI derived regional blood flow and volume parameters, sensitivity remained unchanged at 90% but specificity increased to 80%. In conclusion, we show that dual-echo MRI with a single administration of contrast agent can simultaneously measure both T₁W and T₂*W related perfusion and kinetic parameters in the breast and the combination of DCE MRI and DSC MRI parameters improves the diagnostic performance of breast MRI to differentiate breast cancer from benign fibroadenomas.     

乳腺癌转移相关基因的筛选与生物信息学分析

乳腺癌是女性最常见的恶性肿瘤,转移与复发是乳腺癌患者死亡的主要原因. 研究与乳腺癌细胞转移相关的分子靶点对预防乳腺癌术后复发、提高疗效有重要意义. 本研究以3组乳腺癌转移相关的基因表达谱数据(GSE2034, GSE2603, GSE12276)为分析材料,采用GeneSpring软件筛选乳腺癌原发瘤与转移瘤芯片数据的差异表达基因,结合生物信息学工具PATHER、STRING、pSTIING和文献挖掘工具iHOP对差异基因及其相互作用关系进行分析. 结果显示,共筛选出乳腺癌转移共同差异基因147个,其中表达上调93个,表达下调54个. 这些差异基因主要涉及细胞周期与增殖、细胞粘附、细胞迁移、血管形成及信号转导等生物通路和生物过程. 差异基因编码蛋白间的相互作用主要集中在14个蛋白,且在更为复杂的网络图谱中仍可见其中9个基因（CXCR4、MMP1、MMP2、MMP3、CTGF、COL1A1、MEF2C、PTGS2及SPARC）在重要的节点位置. 文献挖掘发现,COL1A1基因可能为新发现的乳腺癌转移候选基因,为乳腺癌转移的发病机制提供新的思路,也为转移性乳腺癌的分子诊断和个体化治疗奠定基础.     

全数字化乳腺X线摄影诊断临床隐匿型乳腺癌的价值

目的：探讨全数字化乳腺X线摄影对临床隐匿性乳癌的诊断价值。方法：回顾性分析临床扪诊阴性,手术病理证实乳腺癌12例。全部病例均使用全数字化乳腺X线摄影。结果：12例病例发现病灶12个,其中单纯钙化7例,微结节或结构紊乱伴微钙化3例,微结节伴毛刺11例。局部结构紊乱1例。结论：全数字化乳腺X线摄影能清晰显示乳房各个层次结构,尤其发现恶性钙化敏感性高,对发现临床隐匿型乳腺癌具有重大价值。     

乳腺X 线摄影癌周透亮带的影像特征及其病理基础与价值

目的:研究乳腺X线摄影癌周透亮带影像学特征,分析其病理基础及临床意义。方法:回顾性分析2010年6月-2011年10月期间我院经手术病理证实为乳腺癌患者196例,筛选出术前进行过乳腺X线摄影检查并且图像上癌周出现透亮带征象的患者共47例51个病灶,测量肿块直径、癌周透亮带宽度等,与病理大体标本切面和镜下切片进行对比研究分析。结果:双乳病灶多分布于外上象限(19/51),临床触诊病灶大小平均值约35.45±1.25 mm。乳腺X摄影观察病灶均为肿块样,影像测量病灶大小平均值约20.49±1.18 mm,与临床触诊大小之间的差别具有统计学意义(t=2.85,P<0.01);肿块周围可观察到宽窄不均透亮带,平均宽度约15.07±0.86 mm,乳腺癌癌周透亮带宽度与肿块大小之间没有显著相关性(r=0.188,P=0.186)。病理大体标本观察病灶周围包绕一圈连续的黄色脂肪组织;HE染色镜下切片观察瘤灶周围为一圈成熟脂肪细胞,局部被瘤灶边缘增生的致密结缔组织为主的毛刺分割,脂肪组织中散在分布炎性细胞,部分区域见灶状癌细胞团浸润。结论:乳腺X线摄影癌周透亮带病理基础为伴随瘤周间质反应的富含脂肪的组织层,此征象对乳腺癌的诊断、以及临床评估肿瘤浸润范围具有一定意义。     

全数字化乳腺X线摄影诊断临床隐匿型乳腺癌的价值

目的:探讨全数字化乳腺X线摄影对临床隐匿性乳癌的诊断价值。方法:回顾性分析临床扪诊阴性,手术病理证实乳腺癌12例。全部病例均使用全数字化乳腺X线摄影。结果:12例病例发现病灶12个,其中单纯钙化7例,微结节或结构紊乱伴微钙化3例,微结节伴毛刺1例,局部结构紊乱1例。结论:全数字化乳腺X线摄影能清晰显示乳房各个层次结构,尤其发现恶性钙化敏感性高,对发现临床隐匿型乳腺癌具有重大价值。     

Broadband Optical Mammography: Chromophore Concentration and Hemoglobin Saturation Contrast in Breast Cancer

This study reports the optical characterization and quantitative oximetry of human breast cancer using spectrally-resolved images collected with a broadband, continuous-wave optical mammography instrument. On twenty-six cancer patients, we collected two-dimensional optical mammograms and created maps of the concentrations of hemoglobin, water, and lipids, as well as the oxygen saturation of hemoglobin. For each cancerous breast, we analyzed the difference between the tumor region (as identified by x-ray and optical mammography) and the remainder of breast tissue. With respect to the surrounding tissue, we found that cancer regions have significantly higher concentrations of total hemoglobin (+2.4±0.4 μM) and water (+7±1% v/v), and significantly lower lipid concentration (8±2% v/v) and oxygen saturation of hemoglobin (5±1%). We also found a significant correlation between the tumor optical contrast and the grade of breast cancer as quantified by the Nottingham histologic score; this demonstrates how optical signatures may be representative of metabolic and morphological features, as well as the aggressive potential of the tumor.     

X线钼靶摄影和彩超诊断早期乳腺癌比较研究

目的:探讨X线钼靶摄片和彩色多普勒超声对早期乳腺癌的诊断价值.方法:回顾性分析经手术病理证实的76例直径＜1cm较早期乳腺癌的影像学表现,比较两种检查方法的诊断准确性.结果:X线钼靶摄片和彩色多普勒超对早期乳腺癌的诊断符合率分别为92.7%和80.01%,对＞40岁的早期乳腺癌患者的诊断符合率分别为97.1%和75.9%.检出率X线钼靶摄影均明显高于彩超,差异有统计学意义(P＜0.01).结论:钼靶X线撮片和超声都是乳腺疾病最常用的诊断方法,乳腺钼靶摄片对早期乳腺癌的检出率更高,尤其适合于对40岁以上女性的诊断.     

乳腺癌HER2表达与乳腺X线及超声影像表现的相关性分析(英文)

目的:对比分析乳腺癌人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)表达阳性和阴性与乳腺癌的X线及超声影像表现的相关性。方法:对139例雌激素受体(oestrogen receptor ER)、孕激素受体(progesterone receptor PR)表达均阴性的乳腺癌患者术前行X线及超声形态学分析,术后标本测定癌细胞的人类表皮生长因子受体2(HER2)表达情况,比较并分析HER2+/ER-/PR-乳腺癌和HER2-/ER-/PR-乳腺癌影像学的特征性表现,在X线上主要分析:腺体致密度、及病变类型(肿块、钙化、结构紊乱)。其中肿块主要分析形状、边缘、大小;钙化主要分析形态、分布,在超声上主要分析:肿块边缘、有无强回声点、有无腋淋巴结转移,血流情况。结果:HER2+/ER-/PR-乳腺癌在X线上的特征性表现为单纯肿块(x2=8.067,P=0.005)或肿块伴钙化(x2=4.384,P=0.036),棒状、分枝状钙化(x2=5.723,P=0.017),簇状分布(x2=12.110,P=0.007),肿块直径多2cm(x2=4.933,P=0.026),而在腺体致密度、肿块边缘方面差异无统计学意义。超声的特征性表现为肿块伴钙化(x2=16.134,P0.001)、边界不清(x2=9.188,P=0.010)、伴腋下淋巴结转移(x2=5.210,P=0.022),血流方面差异无统计学意义。结论:HER2+/ER-/PR-乳腺癌影像学有特征性表现,X线常表现为单纯肿块或肿块伴钙化,棒状、分枝状钙化,簇状分布,肿块直径多2cm;超声常表现为低回声肿块、边界不清、其内可见点状强回声、常伴腋下淋巴结转移。     

Identification and Quantification of AKT Isoforms and Phosphoforms in Breast Cancer Using a Novel Nanofluidic Immunoassay

Breast cancer subtype-specific molecular variations can dramatically affect patient responses to existing therapies. It is thought that differentially phosphorylated protein isoforms might be a useful prognostic biomarker of drug response in the clinic. However, the accurate detection and quantitative analysis of cancer-related protein isoforms and phospho-isoforms in tumors are limited by current technologies. Using a novel, fully automated nanocapillary electrophoresis immunoassay (NanoPro^TM 1000) designed to separate protein molecules based on their isoelectric point, we developed a reliable and highly sensitive assay for the detection and quantitation of AKT isoforms and phosphoforms in breast cancer. This assay enabled the measurement of activated AKT1/2/3 in breast cancer cells using protein produced from as few as 56 cells. Importantly, we were able to assign an identity for the phosphorylated S473 phosphoform of AKT1, the major form of activated AKT involved in multiple cancers, including breast, and a current focus in clinical trials for targeted intervention. The ability of our AKT assay to detect and measure AKT phosphorylation from very low amounts of total protein will allow the accurate evaluation of patient response to drugs targeting activated PI3K-AKT using scarce clinical specimens. Moreover, the capacity of this assay to detect and measure all three AKT isoforms using one single pan-specific antibody enables the study of the multiple and variable roles that these isoforms play in AKT tumorigenesis.Activation of the PI3K-AKT signaling pathway is one of the most common events in cancer (1, 2). Pathway activation can confer a number of advantages to the cancer cells, including enhanced proliferation and survival (1, 2). Multiple mechanisms exist by which the pathway may become activated, including amplification or activation of receptor tyrosine kinases (e.g. ERBB2 in breast and EGFR in lung tumors), mutation of the catalytic or regulatory subunits of PI3K (e.g. PIK3CA in colorectal and breast tumors), loss of the negative regulator PTEN (e.g. mutation in prostate and melanoma), and gain of function of AKT (e.g. amplification or mutation in breast and pancreatic tumors) (reviewed in Refs. 1 and 2).AKT represents a central node in the PI3K signaling cascade (3). AKT is recruited to the cell membrane via its pleckstrin homology domain when PI3K phosphorylates PIP₂ to form PIP₃ (4, 5). Following recruitment, AKT is phosphorylated by PDK1 and the rictor-mTOR complex, resulting in conformational changes and activation of the protein (5–8). Multiple studies have shown that the phosphorylation of AKT leads to the phosphorylation and activation of downstream effectors of the signaling pathway, such as mTOR complex 1 and S6K (reviewed in Ref. 1). The central role of this pathway in cancer is further underscored by the efforts of multiple pharmaceutical companies that have developed inhibitors against AKT as potential anti-oncogenic therapeutics (9).Despite the importance of AKT in growth and survival signaling in cancer, there are surprisingly few data that address the specific roles played in growth and survival by the multiple AKT family members (AKT-1, -2, and -3) and different phosphorylation and putative phosphorylation sites that can potentially activate the protein. Western blot analysis has been the foundation of most AKT studies, but in many cases pan-AKT antibodies have been employed that fail to distinguish between the different AKT isoforms. Recent siRNA silencing studies have indicated distinct functions for different AKT family members within a cell (10, 11). Moreover, there is evidence in breast cancer that the three isoforms exhibit different localizations and therefore must have at least partially distinct functions (12). Similarly, evidence is mounting for multiple phosphorylation sites in AKT beyond the two most studied phosphorylation events (Thr-308 and Ser-473) (5–8). Phosphorylation at serine and threonine residues at Thr-72 and Ser-246 may be required for the activation or regulation of kinase activity (13). The functional significance of constitutive phosphorylation of Ser-124 and Thr-450 is still unknown (14). Finally, there is evidence that phosphorylation of tyrosine residues at Tyr-315 and Tyr-326 is required for full kinase activity (15).Analysis of such phospho- and isoform-specific activation often requires complicated in-depth analyses using large quantities of proteins, purified recombinant protein, immunoprecipitation, incorporation of ³²P isotopes, and/or mass spectroscopy, which makes such studies more difficult to perform and not easily adaptable to clinical specimens. Thus, better methods are required for the accurate assessment of both phosphoform and isoform usage in cells with an activated PI3K-AKT pathway and the effects of pathway inhibitors using relatively small amounts of starting material. We describe here the development of such an assay using nanocapillary-based isoelectric focusing (16). This approach allows the separation of AKT into distinct peaks that correspond to different iso- and phosphoforms using a small amount of starting material and a single pan-specific antibody. This approach should allow for more accurate determinations of isoform usage in different cell types, as well as of changes in phosphorylation states in response to pathway inhibition, including in clinical specimens.     

Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.     

彩超联合钼靶在未扪及肿块乳腺癌诊断中的应用分析

目的:探讨彩色多普勒超声联合钼靶在未扪及肿块乳腺癌中的临床诊断价值。方法:选取我院乳腺科收治的未扪及肿块乳腺癌患者92例,回顾性分析92例患者术前彩色多普勒超声和钼靶检查结果与手术病理相印证,对比不同的检查方法与病理诊断结果的符合率。结果:单纯彩色多普勒超声检查与单纯钼靶机检查诊断准确率无明显差异(P0.05),而彩色多普勒超声联合钼靶机检查诊断准确率明显高于单纯彩色多普勒超声检查诊断准确率和单纯钼靶机检查诊断准确率,差异有统计学意义(P0.05)。结论:彩色多普勒超声联合钼靶能够明显提高未扪及肿块乳腺癌诊断的准确率,对临床具有指导意义,值得临床推广。     

乳腺癌人类表皮生长因子受体2表达与X线表现的相关性分析

目的：对比分析人类表皮生长因子受体2（HER-2）阳性和阴性乳腺癌X线特征,探讨乳腺癌X线征象与HER-2基因之间的相关性。方法：回顾性分析经手术病理确诊的1153例女性乳腺癌患者的X线表现,根据免疫组织化学结果分为HER-2阳性组（314例）和HER-2阴性组（839例）。对比分析两组乳腺癌肿块和钙化的X线特征,肿块主要分析形态、边界及边缘,钙化主要分析形状及分布形式,并对各项分析结果进行X2检验,P〈0.05为差异性有统计学意义。结果：HER-2阳性组乳腺癌较阴性组多表现为钙化（X2=42.528,P=0.001）,HER-2阴性组乳腺癌X线表现多为单纯肿块（389/839,X2=16.374,P=0.001）。星芒状肿块在HER-2阴性组比例较高（57/514,X2=5.912,P=0.015）,两组类圆形（P=0.480）、分叶状（P=0.111）、不规则形肿块（P=0.152）分布比例则无明显统计学差异。HER-2阳性组乳腺癌肿块边界多模糊不清（X2=8.319,P=0.004）,阴性组肿块边界多为部分清楚（X2=5.818,P=0.016）。HER-2阳性组乳腺癌钙化形态多表现为沙砾状（X2=8.955,P=0.001）、多形性和不定形（X2=7.137,P=0.001）,分布形式无明显统计学差异。结论：HER-2阳性乳腺癌X线表现钙化居多,且多为沙砾状、多形性和不定形钙化,肿块边界多模糊不清;HER-2阴性乳腺癌多表现为单纯肿块,边界多为部分清楚,星芒状肿块多见。     

磁共振肿瘤矩特征信息研究

目的:采用MR脑肿瘤图像分割与矩方法进行结合,以获取特定器官及组织的轮廓。方法:对MR脑肿瘤图像进行分割,并对分割的结果进行矩描述。通过分析当前常用的医学图像分割方法,采用了一种基于形变模型的医学图像分割方法,并按照相应的理论算法模型和实现步骤对医学图像进行了处理,最后用Visual C 6.0编程,并对MR脑肿瘤图像进行分割实验。结果:从切割的图形中可以看出,本分割方法分割边界清晰,总体不确定性较小,利用矩技术所提取的图像特征在基于内容的图像检索中是有效的。结论:本分割方法切实可行,分割效果较好,为进一步的MR脑肿瘤图像分析和研究提供了一种有效工具。     

The Values of Combined and Sub-Stratified Imaging Scores with Ultrasonography and Mammography in Breast Cancer Subtypes

ResultsThese selected cases were evaluated by the “5-point score.” MG, US, and combined and sub-stratified imaging assessments all revealed statistically significant (P < 0.001) incidence of malignancy. The sensitivity was increased in the combined imaging score (99.8%), and the specificity was increased in the sub-stratified combined score (75.4%). In the sub-stratified combined imaging assessment, all BCS can be classified with higher scores (abnormality hierarchy), and luminal B subtype showed the most salient result (hierarchy: higher, 95%; lower, 5%).ConclusionsCombined and sub-stratified imaging assessments can increase sensitivity and specificity of breast cancer diagnosis, respectively, and Luminal B subtype shows the best identification by sub-stratified combined imaging scoring.