乳腺MRI动态增强对良恶性病变的鉴别价值

Objective  

The aim of the study was to discuss the diagnostic value of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in distinguishing malignant tumors of breast from benign lesions.     

动态增强磁共振与乳腺癌分子亚型血管生成的相关性研究

目的 动态增强磁共振成像(dynamic contrast enhanced magnetic resonance imaging,DCE MRI)为乳腺癌敏感度最高的检查方法之一,能够显示病灶血供情况而间接评价病灶微血管生成情况.探讨DCE-MRI半定量参数达峰时间(the time to peak enhancement,TTP)、早期增强率(early-phase enhancement rate,El)、最大线性斜率(SLOPE)与乳腺癌不同分子亚型血管生成的相关性,及比较乳腺癌4种不同分子亚型血管生成的特点.方法 收集山东省肿瘤医院2012-12-01-2015 03 31经手术确诊的103例乳腺癌患者,术前1周内行DCE-MRI扫描,记录上述参数,对切除病变行常规病理和免疫组化检查,根据免疫组化结果分为4种不同分子亚型,观察微血管密度(microvessel density,MVD)计数和血管内皮生长因子(vascular endothelialgrowth factor,VEGF)的表达,并将不同分子亚型DCE-MRI各项参数与免疫组化结果进行相关性分析.结果 4种不同分子亚型的各动态增强参数差异均无统计学意义;三阴型乳腺癌MVD值(79.47±49.79)明显高于Luminal B型(50.89±18.21),P=0.02;除Luminal A型与Luminal B型外,其他各亚型之间VEGF表达差异均有统计学意义,P＜0.001;三阴型乳腺癌的MVD与DCE MRI的关系最密切,r-0.55,P=0.015;MVD与EER、SLOPE呈正相关,r=0.859,P＜0.001;与TTP呈负相关,r=-0.60,P=0.007.Luminal A型乳腺癌MVD与EER(r=0.71,P＜0.001)和SLOPE呈正相关(r=0.51,P=0.001).结论 三阴型乳腺癌较两种Luminal表现为更丰富的血管生成,三阴型及Luminal A型MVD与DCKMRI半定量参数EER、SLOPE存在一定的相关性.     

Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non‐invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB‐neuT mice). Histological examination showed that BALB‐neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE‐MRI results highlighted marked functional changes in terms of vessel permeability (K^trans, volume transfer constant) and vascularisation (v_p, vascular volume fraction) in BALB‐neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE‐MRI biomarkers was observed in BALB‐neuT in comparison to BALB/c mice (K^trans = 5.3 ± 0.7E‐4 and 3.1 ± 0.5E‐4; v_p = 7.4 ± 0.8E‐2 and 4.7 ± 0.6E‐2 for BALB‐neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE‐MRI observations, microvessel counting revealed a significant increase in tumour vessels. Our study showed that DCE‐MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model.     

MRI表观扩散系数对乳腺非肿块样病灶的诊断价值

目的评价表观扩散系数对乳腺MRI非肿块样强化病灶的诊断价值及其与时间信号强度曲线联合应用对诊断效能的影响。方法 68个经手术病理证实的乳腺病灶,根据其不同强化形态分为肿块型与非肿块型两组。测量病灶时间-信号强度曲线并记录曲线类型,并于b=800 s/mm2扩散加权图像上测量病灶ADC值。利用两独立样本t检验比较同一强化形态组中良恶性病灶ADC值的差异。分别绘制曲线类型及ADC值诊断病灶良恶性的ROC曲线,计算曲线下面积、最佳截断点、敏感性、特异性、准确性、阳性预测值、阴性预测值。分析对不同强化形态的病灶,以ADC值作为曲线类型的辅助诊断指标对诊断效能的影响。结果肿块型组中恶性病灶ADC值(0.85±0.09)×10-3mm2/s明显低于良性病灶(1.68±0.32)×10-3mm2/s(P=0.001),非肿块型组中恶性病灶ADC值(1.02±0.19)×10-3 mm2/s亦明显低于良性病灶(1.43±0.31)×10-3 mm2/s(P=0.015)。同一强化形态组,曲线类型与ADC值的ROC曲线下面积均无显著性差异(P值均小于0.05)。对于肿块型组,以ADC值作为曲线类型的辅助诊断指标,诊断效能无显著改变(P=0.549),但可以提高诊断的特异性和阳性预测值(准确性达100%);对于非肿块型组,以ADC值作为曲线类型的辅助诊断工具,诊断效能无显著改变(P=0.709),但可以提高诊断的准确性至87.5%,敏感性和阴性预测值达100%。结论 ADC值对不同强化形态的病灶有辅助诊断作用。     

Breast Lesions： Correlation of Dynamic Contrast Enhancement Patterns on MR images with Tumor Angiogenesis

Objective To determine whether dynamic contrast -enhanced MRI features of the early -phase enhancement rate, enhancement amplitude, and signal-intensity (SI) time course are associated with the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression of malignant and benign breast lesions. Methods Sixty patients with breast lesions, detected with physical examination or conventional mammography, were examined pre —operatively with dynamic contrast-enhanced MRI from December 1998 to June 2000. Of these 60 patients, histopathological correlation was available in 38. These 38 patients(aged 29–73 years) formed the basis of this study. SI changes during dynamic scanning were assessed quantitatively. Early-phase enhancement rate and enhancement amplitude were calculated. Time-SI curves of the lesions were obtained and classified according to their shapes as type I (which was steady enhancement to the end of the dynamic data acquisition at 7.5min.), type II (plateau of SI after avid initial contrast enhancement), or type III (washout of SI after avid initial contrast enhancement). The mean MVD and VEGF expression of the lesions were measured with immunohistochemical staining methods in all the pathologic specimens by a pathologist without knowledge of the results of the MR examination. Care was taken to ensure identical location in the plane of the MR image and pathologic specimens. The relationships among dynamic contrast-enhanced MRI features, MVD, and VEGF expression of benign and malignant breast lesions were analyzed. Results Histology revealed 21 malignancies and 17 benign lesions. The mean MVD and VEGF expression for the 21 malignant lesions were significantly higher than the mean MVD and VEGF expression for the 17 benign lesions (P<0.01). High VEGF expression of benign and malignant breast lesions showed a significant association with increased MVD (P< 0.01 ). Among all 38 lesions, greater (>60%) MR early-phase enhancement rate and time-SI curve type II or III showed a significant association with MVD and VEGF expression. All the differences mentioned above showed statistical significance (P<0.01) except the difference between VEGF expression and the distribution of curve types which had no statistical significance (P=0.069). No significant relationships were observed between the enhancement amplitude and MVD (P>0.05) and VEGF expression (P> 0.05). Regarding the distribution of MVD, the study showed that the greater MVD was most frequently observed at the marginal region of the breast cancers, although the distribution of MVD was heterogeneous in each lesion. Conclusions MVD and VEGF affect the contrast medium enhancement of breast lesions. The early -phase enhancement rate and time — SI curve types of benign and malignant breast lesions are closely related to MVD and VEGF. As a noninvasive method, contrast-enhanced MRI has a potential role in estimating the degree of angiogenesis of breast neoplasms.     

Rim enhancement of breast cancers on contrast-enhanced MR imaging: Relationship with prognostic factors

BACKGROUND: There is little evidence regarding associations between magnetic resonance imaging (MRI) features and other important histopathological prognostic factors of breast cancer. The purpose of our study was to investigate the relationship between rim enhancement on MRI and common histopathological prognostic factors of breast cancers. METHODS: We reviewed the contrast-enhanced MR images of 106 consecutive women with histopathologically verified invasive breast carcinomas. Three radiologists assessed the images of each lesion for the presence of rim enhancement on early and delayed images, which were classified into four patterns. Statistical analyses were performed to explore the associations of these patterns with common histopathological prognostic factors and patient age. RESULTS: Positive ratios of lymph node metastasis and blood vessel invasion and negative ratios of hormone receptors were higher in the invasive cancers with rim enhancement than those without rim enhancement. Rim enhancement was more frequent in invasive ductal cancers with a higher histological grade and larger invasive cancers. The pattern of rim enhancement with centripetal progression showed a significantly increased risk of lymph node metastasis and was associated with a larger size of invasive lesion when compared with the other patterns. Invasive cancers with rim enhancement and little change between the early and delayed images and with centrifugal progression showed significantly less hormone receptor positivity than those without rim enhancement. CONCLUSIONS: Rim enhancement patterns of breast cancers on contrast-enhanced MRI are related to common histopathological prognostic factors and these patterns may be valuable in the preoperative evaluation of breast cancers.     

磁共振动态增强、扩散加权成像联合应用对乳腺疾病的诊断价值

目的 探讨磁共振动态增强（dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI）、扩散加权成像（diffusion weighted imaging,DWI）及其联合应用对乳腺疾病诊断的价值.方法 乳腺病变患者75例,共80个病灶.观察病灶形态、信号特征、时间信号强度曲线（time signal intensity curve,TIC）、早期强化率.联合诊断采用序列诊断及平行诊断两种方法.评价DCE-MRI、DWI及联合成像对乳腺疾病定性诊断的价值.结果 恶性病变形状不规则或呈分叶状、多见毛刺或棘状突起、不均匀强化或环状强化、早期强化明显、TIC多为Ⅲ型.乳腺良性病变多形态规则、边缘清晰、呈均匀强化、早期强化率低、TIC多为Ⅰ型.DCE-MRI联合DWI平行诊断,提高了诊断的灵敏度及准确率,有助于对病变进行定性诊断.结论 DCE-MRI及DWI诊断均有较高的灵敏度、特异度及准确率,推荐作为常规检查序列.联合DCE-MRI和DWI平行诊断,为疾病的诊断提供更丰富、更有价值的信息,诊断的灵敏度和准确率较高,有助于病变性质的判定.     

Differentiation of malignant and benign lung lesions with diffusion-weighted MR imaging

Background

The aim of the study was to evaluate the role of diffusion-weighted magnetic resonance imaging in the differential diagnosis of lung lesions.

Patients and methods.

Sixty-seven patients with lung lesions (48 malignant, 19 benign) were included in this prospective study. Signal intensities (SIs) were measured in diffusion-weighted MR images that were obtained with b=0, 500 and 1000 s/mm² values. Apparent diffusion coefficient (ADC) maps were calculated by using images with b=0 and 1000 s/mm² values. The statistical significance was determined using the Student-t test.

Results

The SIs of malignant lesions were significantly higher than those of benign lesions (p<0.004 for b=0 s/mm² and p<0.000 for the other b values). Using b=500 s/mm², SI≥391 indicated a malignant lesion with a sensitivity of 95%, specificity of 73% and positive predictive value of 87%. Using b=1000 s/mm², SI≥277 indicated a malignant lesion with a sensitivity of 93%, specificity of 69% and positive predictive value of 85%. There was no significant difference between malignant and benign lesions regarding ADC values (p=0.675). There was no significant difference in SIs or ADC values between small cell carcinoma and non-small cell carcinoma. When comparing undifferentiated with well- partially differentiated cancers, SIs were higher with all b values, but the difference was statistically significant only with b=1000 s/mm² (p<0.04).

Conclusions

Diffusion-weighteted MR trace image SI is useful for the differentiation of malignant versus benign lung lesions.     

Differentiation of benign and malignant breast lesions by mechanical imaging

Mechanical imaging yields tissue elasticity map and provides quantitative characterization of a detected pathology. The changes in the surface stress patterns as a function of applied load provide information about the elastic composition and geometry of the underlying tissue structures. The objective of this study is the clinical evaluation of breast mechanical imager for breast lesion characterization and differentiation between benign and malignant lesions. The breast mechanical imager includes a probe with pressure sensor array, an electronic unit providing data acquisition from the pressure sensors and communication with a touch-screen laptop computer. We have developed an examination procedure and algorithms to provide assessment of breast lesion features such as hardness related parameters, mobility, and shape. A statistical Bayesian classifier was constructed to distinguish between benign and malignant lesions by utilizing all the listed features as the input. Clinical results for 179 cases, collected at four different clinical sites, have demonstrated that the breast mechanical imager provides a reliable image formation of breast tissue abnormalities and calculation of lesion features. Malignant breast lesions (histologically confirmed) demonstrated increased hardness and strain hardening as well as decreased mobility and longer boundary length in comparison with benign lesions. Statistical analysis of differentiation capability for 147 benign and 32 malignant lesions revealed an average sensitivity of 91.4% and specificity of 86.8% with a standard deviation of ±6.1%. The area under the receiver operating characteristic curve characterizing benign and malignant lesion discrimination is 86.1% with the confidence interval ranging from 80.3 to 90.9%, with a significance level of P = 0.0001 (area = 50%). The multisite clinical study demonstrated the capability of mechanical imaging for characterization and differentiation of benign and malignant breast lesions. We hypothesize that the breast mechanical imager has the potential to be used as a cost effective device for cancer diagnostics that could reduce the benign biopsy rate, serve as an adjunct to mammography and to be utilized as a screening device for breast cancer detection.     

乳腺X线摄影及磁共振诊断乳腺良恶性病变的性能评价

乳腺癌是女性最常见的恶性肿瘤之一，在全球发病率呈现逐年增高的趋势，严重危害女性健康。目前乳腺X线摄影检查作为筛查及诊断乳腺癌的标准影像检查方法得到了广泛的应用，但其低特异性及敏感性易造成致密乳腺病灶的漏诊及误诊，增加患者不必要的活检几率，MRI检查不仅弥补了X线摄影的不足，其高敏感性及多种成像序列及多方位成像的特点以及绘制TIC曲线、测量感兴趣区ADC值等后处理技术可提供更多的组织结构信息，并进行病灶的良恶性诊断，本文对乳腺X线摄影及磁共振检查诊断乳腺良恶性病变的性能进行了较为详细的综述。     

MRI background parenchymal enhancement,breast density and serum hormones in postmenopausal women

Background parenchymal enhancement (BPE) is the degree to which normal breast tissue enhances on contrast‐enhanced magnetic resonance imaging (MRI). MRI‐density is a volumetric measure of breast density that is highly correlated with mammographic density, an established breast cancer risk factor. Endogenous estrogen concentrations are positively associated with postmenopausal breast cancer risk and BPE has been shown to be sensitive to hormonal exposures. The objective of our study was to examine the relationship between BPE and MRI‐density and serum hormone concentrations in postmenopausal women. This was a study of cancer‐free postmenopausal women undergoing contrast‐enhanced breast MRI (N = 118). At the time of MRI all women completed a self‐administered questionnaire and blood samples were collected for hormone analyses. Serum concentrations of estrone (E1), estradiol (E2) and bioavailable E2 were examined by category of BPE and MRI‐density. Compared to women with “minimal” BPE, those who had “marked” BPE had significantly higher serum concentrations of E1, E2 and bioavailable E2 (90% increase, p_trend across all categories = 0.001; 150% increase, p_trend = 0.001; and 158% increase, p_trend = 0.001, respectively). These associations were only affected to a minor extent by adjustment for BMI and other variables. After adjustment for BMI, no significant associations between MRI‐density and serum E1, E2 and bioavailable E2 were observed. Serum estrogen concentrations were significantly positively associated with BPE. Our study provides further evidence of the hormone‐sensitive nature of BPE, indicating a potential role for BPE as an imaging marker of endogenous and exogenous hormonal exposures in the breast.     

Immunohistochemical demonstration of metallothionein in normal human breast tissue and benign and malignant breast lesions

Metallothioneins (MTs) are a set of low molecular weight proteins with a high binding affinity to metal ions. MT over-expression has been recently demonstrated in invasive ductal carcinoma of the breast with poor clinical prognosis. In the present study, MTs have been immunohistochemically investigated in normal human breast tissue and a variety of benign, pre-invasive, and malignant breast lesions. In normal breast tissue, MTs were present in myoepithelial cells whereas the vast majority of luminal cells were MT negative. In lesions without increased cancer risk (adenosis and scleradenosis), MT was only immunolocalized in myoepithelial cells. In papillomas, MT was also found exclusively in myoepithelial cells. In most cases of epitheliosis, both the luminal and myoepithelial cells expressed MT. Atypicallobular hyperplasia, lobular carcinomain situ, and 13/15 invasive lobular carcinomas showed no MT over-expression. The two invasive lobular carcinomas with MT over-expression were classified as pleomorphic lobular carcinomas with apocrine differentiation. In contrast to lobular cancerization, 12/24 ductalin situ carcinomas and 9/20 invasive ductal carcinomas showed MT over-expression.In situ components found within invasive ductal carcinomas usually reflected the MT status of their invasive counterpart. It is concluded from our immunohistochemical results that breast carcinoma cases with MT overexpression arise from lesions which also show MT overexpression. Thus MT expression in carcinomas may be regarded as a genuine feature of the tumour cells and seems not to be related to endogenous or exogenous factors known to induce MT synthesis.     

Cytogenetics of benign breast lesions

This review summarizes the cytogenetic information on benign breast lesions of various histologies, i.e., fibrocystic lesions from women with and without a known hereditary predisposition to breast cancer, fibroadenomas, phyllodes tumors, and papillomas, and relate the chromosomal features with those in breast carcinoma. In general, the frequency of chromosome abnormalities is lower in benign lesions than in breast cancer, and seems to correlate with the histologic features of the tissue, and the corresponding risk of developing invasive mammary carcinoma; aberrations are more common in proliferative than in nonproliferative lesions. The karyotypes are generally less complex than those detected in invasive carcinoma, and more often involve balanced rearrangements. No lesion-specific aberration has so far been detected; on the contrary, changes repeatedly encountered in breast cancer samples can be found in benign lesions as well, e.g., gain of 1q, interstitial deletion of 3p, and trisomies 7, 18, and 20. Especially intriguing is the prevalence of rearrangements of the short arm of chromosome 3, with the minimally deleted bands 3p13–14, in proliferative lesions from prophylactic mastectomies in breast cancer families. The potential tumor suppressor gene(s) in this region remains, however, to be identified.     

Study of Benign and Malignant Intraductal Lesions of the Breast by Fiberoptic Ductoscopy

OBJECTIVE To observe and subtype the appearance of intraductal papilloma (lesions) and of infiltrating ductal carcinoma or early infiltrating ductal carcinoma using a fiberoptic ductoscope (FDS) examination, and to discuss the differentiation and diagnosis of benign and malignant tumors by FDS.METHODS The characteristics of FDS images and diagnostic data for 229patients with intraductal papilloma (lesions) and 50 patients with ductal carcinoma, who were confirmed by surgical pathology from October 1998 to December 2003, were analyzed retrospectively.RESULTS The appearance of the lesions observed by FDS were grouped into 4 types: a monothelia (type Ⅰ), polythelia (type Ⅱ), superficies (type Ⅲ)and a mixture (type Ⅳ). Intraductal papillomas (lesions) were more commonly seen in type Ⅰ and Ⅱ, and intraductal carcinomas or early infiltrating ductal carcinomas were more commonly seen in type Ⅲ and Ⅳ;there was a statistically significant difference in the distribution of the ductoscopic types, except in type Ⅱ, between the two types of lesions, P＜0.001. The focal detection rate by FDS for intraductal papilloma and papillomatosis was 99.6% (228/229) and for breast cancer was 96.0% (48/50). The diagnostic accuracy was 97.8% (224/229) and 82.0% (41/50),respectively.CONCLUSION FDS can be a guide for the treament of benign and malignant intraductal tumors, with early discovery and accurate diagnosis.     

乳管内良恶性肿瘤的乳管内视镜下鉴别诊断研究

目的 :对导管内乳头状瘤 (病 )和导管内癌或早期浸润性导管癌的乳管内视镜(fiberopticductoscope ,FDS)下表现进行观察及分型 ,探讨FDS下乳管内良恶性肿瘤的鉴别诊断。方法 :回顾分析了 1998年 10月 1日～ 2 0 0 3年 12月 3 1日手术病理确诊的 2 2 9例导管内乳头状瘤 (病 )和 5 0例导管癌患者的FDS图象特征和诊断资料。结果 :将其镜下表现分为单乳头型 (Ⅰ型 )、多乳头型 (Ⅱ型 )、表面型 (Ⅲ型 )和混合型 (Ⅳ型 )。导管内乳头状瘤 (病 )多见于Ⅰ型和Ⅱ型 ,导管内癌或早期浸润性导管癌多见于Ⅲ型和Ⅳ型。两者在Ⅰ、Ⅲ、Ⅳ型的分布上差异有统计学意义 ,P <0 0 0 1。但在Ⅱ型的分布上差异无统计学意义。FDS对两者的病灶检出率分别为 99 6%( 2 2 8/2 2 9)和 96 0 % ( 4 8/5 0 ) ,诊断准确率分别为 97 8% ( 2 2 4/2 2 9)和 82 0 % ( 4 1/5 0 )。结论 :FDS能早期发现乳管内良恶性肿瘤 ,诊断准确性高 ,对治疗有指导意义     

多参数磁共振成像对乳腺良恶性病变的诊断价值

目的 探讨扩散加权成像(DWI)、T2加权成像(T2WI)和动态对比增强(DCE)-MRI对乳腺癌的诊断价值.方法 对136例患者的169个乳腺病变进行分析,所有患者同时接受了DCE-MRI和DWI(b值为1000 s/mm2)检查.按检查方法分为三组,第一组DCE-MRI,第二组DWI-T2WI,第三组DCE-MRI...     

Nuclear morphometry of benign and malignant breast lesions

The mean nuclear area (MNA) of mammary gland epithelium was measured in 403 breast specimens, comprising 239 invasive carcinomas, 49 carcinomas in situ, 45 cases of fibrocystic disease (f.c.d.) with intraductal epithelial hyperplasia, and 60 cases of f.c.d. without intraductal hyperplasia. Normal breast tissue adjacent to other benign or malignant lesions was measured in 170 specimens. Statistical analysis revealed no difference between the MNA of invasive ductal carcinoma and ductal carcinoma in situ. The MNA of lobular and ductal carcinomas were significantly different. Significant differences were also found between ductal carcinoma and the two classes of f.c.d. The MNA of f.c.d. with and without intraductal hyperplasia were also significantly different, the former having the highest MNA. All breast lesions showed MNA significantly higher than that of normal breast epithelium. These findings show that there is a gradual increase in MNA from the baseline value of normal breast epithelium, via fibrocystic disease without and with intraductal proliferation to invasive carcinomas. Measurement of MNA may aid in pinpointing cases of intraductal epithelial hyperplasia with malignant potential.     

Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

Background:

Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer.

Methods:

We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women.

Results:

We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers.

Conclusion:

Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours.