Histological and electron microscopic features of the extracellular matrix of invasive breast ductal carcinoma of no special type. Report of 5 cases and literature review.

Invasive ductal carcinoma of no special type is the most common type of breast cancer. In light of the above, many authors have reported the histological and electron microscopic characteristics of these tumors. On the other hand, a limited number of works exist where the authors have concentrated on investigating the extracellular matrix. This article presents data received as the results of light and electron microscopic examination of the extracellular matrix, angiogenesis, and cellular microenvironment of invasive breast ductal carcinoma of no special type. The authors have shown that the processes of stroma formation in the IDC NOS type are associated with the presence of fibroblasts, macrophages, dendritic cells, lymphocytes, and other cells. It was also shown the detailed interaction of the above cells with each other, as well as with vessels and fibrillar proteins such as collagen and elastin. The microcirculatory component is characterized by histophysiological heterogeneity, which manifests as the activation of angiogenesis, relative vascular differentiation, and regression of individual microcirculation components.

Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.

PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors. CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκß pathway.

Predicting breast cancer response to neoadjuvant chemotherapy based on tumor vascular features in needle biopsies.

In clinical breast cancer intervention, selection of the optimal treatment protocol based on predictive biomarkers remains an elusive goal. Here, we present a modeling tool to predict the likelihood of breast cancer response to neoadjuvant chemotherapy using patient specific tumor vasculature biomarkers. A semi-automated analysis was implemented and performed on 3990 histological images from 48 patients, with 10-208 images analyzed for each patient. We applied a histology-based model to resected primary breast cancer tumors (n = 30), and then evaluated a cohort of patients (n = 18) undergoing neoadjuvant chemotherapy, collecting pre- and post-treatment pathology specimens and MRI data. We found that core biopsy samples can be used with acceptable accuracy (r = 0.76) to determine histological parameters representative of the whole tissue region. Analysis of model histology parameters obtained from tumor vasculature measurements, specifically diffusion distance divided by radius of drug source (L/rb) and blood volume fraction (BVF), provides a statistically significant separation of patients obtaining a pathologic complete response (pCR) from those that do not (Student's t-test; P < 0.05). With this model, it is feasible to evaluate primary breast tumor vasculature biomarkers in a patient specific manner, thereby allowing a precision approach to breast cancer treatment.

Role of nestin expression in angiogenesis and breast cancer progression.

Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical (IHC) analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki­67. We evaluated nestin expression in tumour and endothelial cells, Ki­67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA­MB­231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA­MB­231 and BO2 cells than in MCF-7 and SK-BR-3 cells.

Mapping breast cancer blood flow index, composition, and metabolism in a human subject using combined diffuse optical spectroscopic imaging and diffuse correlation spectroscopy.

Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are model-based near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, ? a , and reduced scattering, ? s ? ) and blood flow (blood flow index, BFI), respectively. DOSI-derived ? a values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin ( HbO 2 , HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 ?? mm ? 1 (37%) in ? s ? and 0.003 ?? mm ? 1 (33%) in ? a lead to ? 53 % and 9% errors in BFI, respectively. DOSI/DCS imaging of a solid tissue-simulating flow phantom and

[Development of an Innovative Cell Isolation Method for the Investigation of Breast Cancer Pathogenesis and Angiogenesis for Experimental In Vitro And In Vivo Assays]. / Entwicklung eines neuen Zellisolationsverfahrens zur Erforschung der Mammakarzinompathogenese und -angiogenese für experimentelle in vitro und in vivo Assays.

Background Breast cancer is the world's most common cancer among women. Autologous lipotransfer is increasingly used for breast reconstruction following surgical removal of the tumour. In cell-assisted lipotransfer, the transplant is enriched with stem cells from adipose tissue (ADSC). Despite positive clinical results, there are some concerns regarding oncological safety due to transplanted stem cells. To date there are only a few breast cancer studies using primary cells from the same patient to enable further investigation into the complexity of cell-cell interactions in breast cancer in an experimental setting. Materials and methods We performed literature research on the topic of autologous lipotransfer. 5 different cell types (epithelial, mesenchymal cells, ADSC, endothelial cells, endothelial progenitor cells) were isolated from mammary (carcinoma) tissue or blood and were subsequently characterised for gene and protein expression as well as functional properties. The arteriovenous (AV) loop model in the rat was evaluated as a possible in vivo model for breast cancer pathogenesis and angiogenesis in this study. Results The literature provided evidence for an in-vitro interaction between ADSC and cells of the mammary (carcinoma) tissue. In some clinical studies, certain subgroups of patients appeared to be exposed to an increased risk of tumour recurrence after lipotransfer, but in most studies no correlation between lipotransfer and tumour recurrence was found. Different cell populations, which differed significantly in terms of surface markers, gene expression and functional properties, were isolated from tissue of the same patient. Axial vascularised tissue was successfully generated in the AV loop model. Conclusion In this study we were able to isolate different cell populations from the same patient, which reflect the heterogeneity of the tumour tissue. This enables a precise analysis of cell-cell interactions and their effects on tumour angiogenesis and pathogenesis in breast cancer. In combination with the AV loop model, this offers new possibilities to generate vascularised mammary carcinoma tissue as well as healthy mammary gland tissue in vivo as an optimal model for the clinical setting.

Visualization of tumor-related blood vessels in human breast by photoacoustic imaging system with a hemispherical detector array.

Noninvasive measurement of the distribution and oxygenation state of hemoglobin (Hb) inside the tissue is strongly required to analyze the tumor-associated vasculatures. We developed a photoacoustic imaging (PAI) system with a hemispherical-shaped detector array (HDA). Here, we show that PAI system with HDA revealed finer vasculature, more detailed blood-vessel branching structures, and more detailed morphological vessel characteristics compared with MRI by the use of breast shape deformation of MRI to PAI and their fused image. Morphologically abnormal peritumoral blood vessel features, including centripetal photoacoustic signals and disruption or narrowing of vessel signals, were observed and intratumoral signals were detected by PAI in breast cancer tissues as a result of the clinical study of 22 malignant cases. Interestingly, it was also possible to analyze anticancer treatment-driven changes in vascular morphological features and function, such as improvement of intratumoral blood perfusion and relevant changes in intravascular hemoglobin saturation of oxygen. This clinical study indicated that PAI appears to be a promising tool for noninvasive analysis of human blood vessels and may contribute to improve cancer diagnosis.

Correlation of microvessel parameters in invasive ductal carcinoma of the breast and fibroadenomas: a morphometric study.

Modifications of microvascular configuration are essential features encountered during the progression of breast tumors. Our objectives were to correlate morphometrically evaluated microvessel parameters (microvessel density [MVD], microvessel caliber [VC], microvessel cross-sectional area [VCSA], percentage of total VCSA [%TVCSA], and total microvessel boundary density [TVBD]) with histologic grades of invasive ductal carcinoma (IDC) of the breast and benign breast lesions. Sixty cases of IDC presented with modified radical mastectomy, and 20 benign breast fibroadenomas were evaluated for various microvessel parameters, using CD34-immunostained histologic sections by computerized image morphometry. Samples were divided into 4 histologic groups: benign, grade 1, grade 2, and grade 3; mean with SD and range was evaluated for each group. Histologic grades showed a strong positive correlation with %TVCSA (ρ=0.773) and TVBD (ρ=0.811) and a moderate positive correlation with MVD (ρ=0.607), VC (ρ=0.609), and VCSA (ρ=0.616) when analyzed for all samples of the 4 groups. Except MVD, all parameters including age was the lowest (P<.001) for the benign group. Among the IDCs, differences of mean VC and VCSA were not significant; MVD, %TVCSA, and TVBD were the lowest in grade 1 and the highest in grade 3. Upper cutoff value of benign lesions for MVD was 155mm-2; VC, 9.94µm; VCSA, 94.42 µm2; %TVCSA, 1.33; and TVBD, 4.37mm-1. Total microvessel boundary density included the information of microvessel concentration and size showed the best correlation with grades. Microvessel density showed a positive correlation with grades in the IDCs, but for the differentiation of benign from malignant, VC, VCSA, %TVCSA, and TVBD showed excellent area under the receiver operating characteristic curve (area under the curve > 0.990), unlike MVD (area under the curve = 0.797).

Comparison of Microvessel Density with Prognostic Factors in Invasive Ductal Carcinomas of the Breast.

OBJECTIVE: Angiogenesis plays a key role in tumor growth and metastasis. Determination of microvessel density is the most common technique used to evaluate the amount of the intratumoral angiogenesis in breast cancer. We have aimed to investigate the relationship with tumor angiogenesis and prognostic parameters in breast invasive ductal carcinomas. MATERIAL AND METHOD: In this study, a total of 100 invasive ductal carcinoma patients, who were diagnosed at the Department of Pathology, Ataturk University Faculty of Medicine between the years 2003-2008, were re-evaluated. Patient characteristics and clinicopathological findings were obtained from archival records. In the present study, microvessel density was determined by immunohistochemical staining by using anti-CD34 monoclonal antibody in the paraffin blocks. First, the most vascular area was selected in the tumor under a low magnification (40x) by a light microscope and then microvessels were counted under a higher magnification (200x). Patients were classified as low and high microvessel density depending on their microvessel counts. Chi-square test and multivariate linear regression analysis were used for statistical analysis (p≤0.05). RESULTS: We have determined that microvessel density increases as tumor size increases (p=0.001). Microvessel density was higher in patients with at least 10 lymph node metastases compared to those with no metastasis (p=0.05). However, there was no statistically significant difference between microvessel density and other prognostic factors such as histological grade, nuclear grade, patient age, vascular invasion, estrogen, progesterone receptor status, HER2/neu expression. CONCLUSION: In our study, we have found that microvessel density is associated with tumor size and lymph node metastasis in patients with invasive ductal carcinoma.

Hypervascularity Predicts Complete Pathologic Response to Chemotherapy and Late Outcomes in Breast Cancer.

BACKGROUND: Our objective was to investigate the relationship between asymmetric increase in breast vascularity (AIBV) and pathologic profiles of breast cancer. We also addressed the prognostic performance of AIBV and of vascular maps reduction after neoadjuvant chemotherapy (NAC) in predicting pathologic complete response (pCR) at surgery and outcome at follow-up. MATERIALS AND METHODS: Two hundred nineteen patients with unilateral locally advanced breast cancer (LABC) underwent magnetic resonance imaging before and after NAC. Axial, sagittal, and coronal maximum intensity projections were obtained in a subjective comparative evaluation. Asymmetrical versus symmetrical breast vascularity was defined through number of vessels, diameter, and signal intensity. Kaplan-Meier methodology was employed for late survival (31.4 ± 18 months follow-up). RESULTS: AIBV ipsilateral to LABC occurred in 62.5% (P < .001). AIBV was significantly associated with invasive ductal carcinoma, G3, triple-negative, HER2+, and hybrid phenotypes (P < .001). pCR was more frequent among patients with AIBV (24%) (P = .001). After NAC, the vascular map was significantly reduced, particularly in patients with pCR (P < .001). At follow-up, the recurrence rate was 22% (6.1% mortality). AIBV after NAC was associated with worse late survival (P = .036). A trend towards worse late survival existed among patients with AIBV before NAC. We did not observe statistically different survival according to the variation of vascularity after NAC. CONCLUSION: LABC with ipsilateral AIBV before NAC is associated with more aggressive pathologic profiles. Nonetheless, it is more sensitive to NAC and shows a higher frequency of pCR. The persistence of AIBV after NAC entails a worse late prognosis and should prompt more aggressive therapeutic strategies.

Damage effect of high-intensity focused ultrasound on breast cancer tissues and their vascularities.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive therapy that makes entire coagulative necrosis of a tumor in deep tissue through the intact skin. There are many reports about the HIFU's efficacy in the treatment of patients with breast cancer, but randomized clinical trials are rare which emphasize on the systematic assessment of histological changes in the ablated tumor vascularities, while clinical trials utilizing bevacizumab and other anti-angiogenic drugs in breast cancer have not demonstrated overall survival benefit. The purpose of this study is to evaluate the damage effect of HIFU on breast cancer tissues and their vascularities. METHODS: Randomized clinical trials and the modality of treat-and-resect protocols were adopted. The treated outcome of all patients was followed up in this study. The target lesions of 25 breast cancer patients treated by HIFU were observed after autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau's histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEAI); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy. RESULTS: The average follow-up time was 12 months; no local recurrence or a distant metastatic lesion was detected among treated patients. Histological examination of the HE slides indicated that HIFU caused coagulative necrosis in the tumor tissues and their vascularities: all feeder vessels less than 2 mm in diameter in the insonated tumor were occluded, the vascular elasticity provided by fibrin was lost, the cells were disordered and delaminated, and UEAI staining of the target lesions was negative. Immediately after HIFU irradiation, the tumor capillary ultrastructure was destroyed, the capillary endothelium was disintegrated, the peritubular cells were cavitated, and the plasma membrane was incomplete. CONCLUSIONS: HIFU ablation can destroy all proliferating tumor cells and their growing vascularities simultaneously; this may break interdependent vicious cycle of tumor angiogenesis and neoplastic cell growth that results in infinite proliferation. While it cannot cause tumor resistance to HIFU ablation, it may be a new anti-angiogenic strategy that needs further clinical observation and exploration. Furthermore, the treatment indications of HIFU ablation were reviewed and discussed in this manuscript.

Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases.

UNLABELLED: Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. AIM: The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. METHODS: 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. RESULTS: High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). CONCLUSION: Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer.

Breast contrast-enhanced MR imaging: semiautomatic detection of vascular map.

BACKGROUND: The diagnostic value of breast vascular maps using contrast-enhanced MR imaging has recently been explored. We propose a semiautomatic method to obtain breast vascular maps and to measure the number of blood vessels in the breast. METHODS: From January 2011 to December 2013, 188 patients underwent breast contrast-enhanced MRI; patients with unilateral and histopathologically confirmed breast lesions were included in this study; 123 patients had malignant lesions and 65 patients had benign tissue diagnoses. Breast semiautomatic vascular map detection was performed using Hessian matrix-based method and morphologic operators. Blood vessels detection was compared with radiologic interpretation findings to evaluate algorithm goodness. Increase in vascularity associated with ipsilateral cancer was also assessed. Chi square test was used to observe statistically significant difference. RESULTS: A total of 1315 blood vessels were identified using semiautomatic procedure; 1034 were correctly classified (78.7 %), 261 (19.8 %) were incorrectly classified, and 20 (1.5 %) were missing. A significant association was found between one-sided increased breast vascularity and ipsilateral malignancy (p < 0.001). CONCLUSIONS: In conclusion, detection of vascularity increase as risk factor for developing breast cancer could be performed with semiautomatic vascular mapping of contrast-enhanced MR imaging.

Tumor Angiogenesis in Breast Cancer: Pericytes and Maturation Does Not Correlate With Lymph Node Metastasis and Molecular Subtypes.

BACKGROUND: Angiogenesis, traditionally assessed by microvessel density (MVD), does not give an indication of the functional status of the tumor neovasculature. The structural and functional stability of the tumor vasculature and its potential clinical relevance in breast cancer was evaluated. MATERIALS AND METHODS: In invasive breast cancer, immunostaining of endothelial cells and pericytes was performed using anti-CD34 and anti-platelet-derived growth factor receptor-ß antibody, respectively. Double immunostaining for the proliferating capillary index (PCI) and microvessel pericyte coverage index (MPI) was performed with CD34/Ki-67 and CD34/smooth muscle actin. RESULTS: The mean MVD of 145 vessels/mm(2) was significantly greater in grade 3 tumors (P = .018) and in necrotic tumors (P = .022). The PCI ranged from 0% to 17.14% (mean, 4.37%) and was associated with a high proliferative index in tumor tissue (P = .044). The MPI ranged from 13.09% to 88.18% (mean, 41.35%), indicating the stability of the tumor vasculature. However, it was not significantly associated with the tumor size, tumor grade, lymph node metastasis, proliferative index, or molecular subtypes. CONCLUSION: MVD remains the angiogenesis-related parameter associated with tumor grade and necrosis. The PCI was the only functional parameter of angiogenesis associated with a poor prognostic indicator. The MPI did not show any correlation with the known prognostic and predictive factors.

Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report.

The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer.

The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3ß/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.

Association of ultrasonographic features with NGX6 expression and prognosis in invasive ductal breast carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a newly discovered tumor suppressor gene. It contains one epidermal growth factor (EGF)-like domain. Many studies have shown that proteins contain (EGF)-like domain structure affect a variety of biological actions. However, little is known about the relationships between NGX6 expression and biological behaviors in invasive ductal breast carcinoma (IDBC). The study discussed the association of ultrasonographic features with NGX6 expression and prognosis in IDBC. METHODS: Ultrasonographic feature and clinical data in 122 patients with IDBC were retrospectively analyzed. NGX6 expression of IDBC was measured using immunohistochemistry methods. RESULTS: The incidence of the burr sign, lymph node metastasis and abundance blood flow in NGX6 expression negative groups were higher than those in positive groups. Kaplan-Meier analysis showed that the association between NGX6 positive expression and higher disease-free survival (DFS) or higher overall survival (OS); Lymph node metastasis is associated with lower DFS or lower OS; Lower blood flow grade is associated with higher DFS. In univariate and multivariate survival analysis, NGX6 expression, lymph node metastasis, TNM and the blood flow grade were the independent prognostic factors for DFS and OS of IDBC. CONCLUSIONS: ultrasonographic features are associated with NGX6 expression in IDBC. NGX6 is involved in the invasion and metastasis activity of IDBC. Our results suggest that NGX6 may be employed as a promising prognostic factor and useful therapeutic target for IDBC. Combination of ultrasonic findings and NGX6 detection may yield clinically useful information for IDBC prognosis.

Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas.

Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.