Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds.

The treatment of wounds using the body's own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)+ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP+ vascular and lymph vessel fragments, which interconnected with the GFP- vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management.

Lymph Vessels Associate with Cancer Stem Cells from Initiation to Malignant Stages of Squamous Cell Carcinoma.

Tumor-associated lymph vessels and lymph node involvement are critical staging criteria in several cancers. In skin squamous cell carcinoma, lymph vessels play a role in cancer development and metastatic spread. However, their relationship with the cancer stem cell niche at early tumor stages remains unclear. To address this gap, we studied the lymph vessel localization at the cancer stem cell niche and observed an association from benign skin lesions to malignant stages of skin squamous cell carcinoma. By co-culturing lymphatic endothelial cells with cancer cell lines representing the initiation and promotion stages, and conducting RNA profiling, we observed a reciprocal induction of cell adhesion, immunity regulation, and vessel remodeling genes, suggesting dynamic interactions between lymphatic and cancer cells. Additionally, imaging analyses of the cultured cells revealed the establishment of heterotypic contacts between cancer cells and lymph endothelial cells, potentially contributing to the observed distribution and maintenance at the cancer stem cell niche, inducing downstream cellular responses. Our data provide evidence for an association of lymph vessels from the early stages of skin squamous cell carcinoma development, opening new avenues for better comprehending their involvement in cancer progression.

Changes and effects of lymphatic vessels and lymphatic endothelial cells in lymph node metastasis of esophageal cancer / 中国胸心血管外科临床杂志

@#The lymphatic system is the main way of tumor metastasis and diffusion. Esophageal cancer is one of the typical cancers that are prone to metastasis through the lymphatic system. At present, an increasing number of studies show that the interaction between tumor cells and lymphatic endothelial cells is the first step in tumor lymphatic metastasis, but the underlying molecular mechanism is unclear. This article reviews the role and changes of tumor-related lymphatic vessels and lymphatic endothelial cells in the process of tumor lymphatic metastasis, which lays a foundation for further study of the specific molecular mechanism of esophageal cancer lymphatic metastasis and provides a new treatment direction for esophageal cancer patients.

Case Report: Multiple Cavernous Pericardial Lymphangioma (Pericardial Lymphangiomatosis) in a Captive Peregrine Falcon (Falco peregrinus brookei).

A 12-year-old female peregrine falcon (Falco peregrinus brookei) from a private raptor breeding facility that presented a good body condition, died suddenly without showing previous symptoms. At necropsy, in the coelomic cavity, multiple cystic structures demarcated by a thin transparent wall and filled with a serous content were observed. They were firmly adhered to the cranial part of the epicardium and adjacent tissues and occupied the entire thoracic area of the coelomic cavity. Microscopically, emerging simultaneously from several areas the epicardium, multiple irregular channels and cystic spaces, lined by a single endothelial cell layer and separated by fibrovascular septa containing smooth muscle tissue, were observed. Immunohistochemical examination revealed that the neoplastic endothelial cells positively immunolabelled for the pan-endothelial marker factor VIII-related antigen but immunostained negative for cytokeratins (PCK26) while strong positivity for sarcomeric α-smooth muscle actin (α-SMA) was detected in the cystic walls. Based on the morphological and immunohistochemical findings, lesions were determined as consistent with a multiple cavernous pericardial lymphangioma, or pericardial lymphangiomatosis, a rare vascular neoplasm. The animal also showed a diffuse chronic perihepatitis, a necrotic area in the liver and foci of cartilaginous metaplasia and calcification in the aorta and vena cava. Literature review, particularly on the epidemiology of lymphangioma, demonstrated the rarity of this tumor in the different animal species and in this location, particularly in birds, being the first report of this type of tumor in a peregrine falcon.

Use of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration.

Impaired wound healing represents an unsolved medical need with a high impact on patients´ quality of life and global health care. Even though its causes are diverse, ischemic-hypoxic conditions and exacerbated inflammation are shared pathological features responsible for obstructing tissue restoration. In line with this, it has been suggested that promoting a normoxic pro-regenerative environment and accelerating inflammation resolution, by reinstating the lymphatic fluid transport, could allow the wound healing process to be resumed. Our group was first to demonstrate the functional use of scaffolds seeded with photosynthetic microorganisms to supply tissues with oxygen. Moreover, we previously proposed a photosynthetic gene therapy strategy to create scaffolds that deliver other therapeutic molecules, such as recombinant human growth factors into the wound area. In the present work, we introduce the use of transgenic Synechococcus sp. PCC 7002 cyanobacteria (SynHA), which can produce oxygen and lymphangiogenic hyaluronic acid, in photosynthetic biomaterials. We show that the co-culture of lymphatic endothelial cells with SynHA promotes their survival and proliferation under hypoxic conditions. Also, hyaluronic acid secreted by the cyanobacteria enhanced their lymphangiogenic potential as shown by changes to their gene expression profile, the presence of lymphangiogenic protein markers and their capacity to build lymph vessel tubes. Finally, by seeding SynHA into collagen-based dermal regeneration materials, we developed a viable photosynthetic scaffold that promotes lymphangiogenesis in vitro under hypoxic conditions. The results obtained in this study lay the groundwork for future tissue engineering applications using transgenic cyanobacteria that could become a therapeutic alternative for chronic wound treatment. STATEMENT OF SIGNIFICANCE: In this study, we introduce the use of transgenic Synechococcus sp. PCC 7002 (SynHA) cyanobacteria, which were genetically engineered to produce hyaluronic acid, to create lymphangiogenic photosynthetic scaffolds for dermal regeneration. Our results confirmed that SynHA cyanobacteria maintain their photosynthetic capacity under standard human cell culture conditions and efficiently proliferate when seeded inside fibrin-collagen scaffolds. Moreover, we show that SynHA supported the viability of co-cultured lymphatic endothelial cells (LECs) under hypoxic conditions by providing them with photosynthetic-derived oxygen, while cyanobacteria-derived hyaluronic acid stimulated the lymphangiogenic capacity of LECs. Since tissue hypoxia and impaired lymphatic drainage are two key factors that directly affect wound healing, our results suggest that lymphangiogenic photosynthetic biomaterials could become a treatment option for chronic wound management.

Inflammation Precedes Fat Deposition in an Experimental Model of Lymphedema.

Background: Chronic lymphedema is a common complication of lymphatic obstruction, particularly after cancer treatment, characterized by an increased volume of the affected extremity, partly caused by the accumulation of excessive adipose tissue. The relationship between lymph vessels' obstruction and fat deposit is, however, poorly understood. Objective: Our central hypothesis was that the inflammatory process caused by lymph stasis precedes the adipocyte differentiation and fat deposition. Methods and Results: We used a modified mouse tail model to produce secondary lymphedema. Animals were treated with dexamethasone, or the procedure was performed in nitric oxide synthase 2 (NOS2)-deficient mice to evaluate the role of inflammation in lymphedema formation. Adipose tissue (Lipin) and inflammatory markers (IL-6, MCP-1, and F4-80) were analyzed in histological samples and by quantitative polymerase chain reaction. We observed an increased deposition of fat into the affected area that starts 3 weeks after lymph vessel ligation; it further increased after 6 weeks. Genes involved in the inflammatory process were upregulated before adipocyte maturation. Treatment with dexamethasone or the use of inducible nitric oxide synthase knockout mice blocked the inflammatory reaction and inhibited the accumulation of fat distal to the lymphatic obstruction. Conclusion: In the modified mouse tail lymphedema, inflammation precedes adipogenesis. Our data suggest that MCP-1 and nitric oxide may be potential targets for lymphedema management.

Distinct roles of VE-cadherin for development and maintenance of specific lymph vessel beds.

Endothelial cells line blood and lymphatic vessels and form intercellular junctions, which preserve vessel structure and integrity. The vascular endothelial cadherin, VE-cadherin, mediates endothelial adhesion and is indispensible for blood vessel development and permeability regulation. However, its requirement for lymphatic vessels has not been addressed. During development, VE-cadherin deletion in lymphatic endothelial cells resulted in abortive lymphangiogenesis, edema, and prenatal death. Unexpectedly, inducible postnatal or adult deletion elicited vessel bed-specific responses. Mature dermal lymph vessels resisted VE-cadherin loss and maintained button junctions, which was associated with an upregulation of junctional molecules. Very different, mesenteric lymphatic collectors deteriorated and formed a strongly hyperplastic layer of lymphatic endothelial cells on the mesothelium. This massive hyperproliferation may have been favored by high mesenteric VEGF-C expression and was associated with VEGFR-3 phosphorylation and upregulation of the transcriptional activator TAZ Finally, intestinal lacteals fragmented into cysts or became highly distended possibly as a consequence of the mesenteric defects. Taken together, we demonstrate here the importance of VE-cadherin for lymphatic vessel development and maintenance, which is however remarkably vessel bed-specific.

Three-Dimensional Visualization of the Lymphatic Vasculature.

Like the circulatory blood vessel system, the dendriform lymphatic vascular system forms a disseminated organ that is virtually indispensible for the function of most other organs. Formation and maintenance of the correct topology are essential for lymph vessel physiology and hence analysis of its three-dimensional architecture provides crucial functional information.Here we describe protocols for whole-mount immunostaining of the vessel systems in various mouse tissues, mouse fetuses, and human skin biopsies. The resulting samples are suited after flat mounting for confocal microscopy or after optical tissue clearing for light sheet microscopy. Both microscopic modalities use optical sectioning to generate image stacks from which the three-dimensional vessel structure can be digitally reconstructed. We introduce the open software package Voreen, developed at the University of Münster. Voreen has been adapted and extended for the interactive visualization of large multichannel image stacks on commodity hardware, allowing for a faithful digital representation of the spatial structure of the vessel systems in whole-mount stained tissue samples.

Visualization of murine lymph vessels using photoacoustic imaging with contrast agents.

Metastasis frequently occurs even in the early stage of breast cancer. This research studied the feasibility of using photoacoustic (PA) imaging for identifying metastasis in the lymph vessels of mice. The photoacoustic efficiency of various contrast agents was investigated, and the influence of scattered light was evaluated by using a lymph vessel phantom. The lymph vessels of mice were then visualized using the selected contrast agents: indocyanine green (ICG) and gold nanorods (AuNR). The attenuation of the PA imaging was -1.90 dB/mm, whereas that of the fluorescence imaging was -4.45 dB/mm. The results indicate the potential of identifying sentinel lymph nodes by using PA imaging with these contrast agents.

The anatomy of the thoracic duct at the level of the diaphragm: A cadaver study.

BACKGROUND: Injury and subsequent leakage of unrecognized thoracic duct tributaries during transthoracic esophagectomy may lead to chylothorax. Therefore, we hypothesized that thoracic duct anatomy at the diaphragm is more complex than currently recognized and aimed to provide a detailed description of the anatomy of the thoracic duct at the diaphragm. BASIC PROCEDURES: The thoracic duct and its tributaries were dissected in 7 (2 male and 5 female) embalmed human cadavers. The level of origin of the thoracic duct and the points where tributaries entered the thoracic duct were measured using landmarks easily identified during surgery: the aortic and esophageal hiatus and the arch of the azygos vein. MAIN FINDINGS: The thoracic duct was formed in the thoracic cavity by the union of multiple abdominal tributaries in 6 cadavers. In 3 cadavers partially duplicated systems were present that communicated with interductal branches. The thoracic duct was formed by a median of 3 (IQR: 3-5) abdominal tributaries merging 8.3cm (IQR: 7.3-9.3cm) above the aortic hiatus, 1.8cm (IQR: -0.4 to 2.4cm) above the esophageal hiatus, and 12.3cm (IQR: 14.0 to -11.0cm) below the arch of the azygos vein. CONCLUSION: This study challenges the paradigm that abdominal lymphatics join in the abdomen to pass the diaphragm as a single thoracic duct. In this study, this occurred in 1/7 cadavers. Although small, the results of this series suggest that the formation of the thoracic duct above the diaphragm is more common than previously thought. This knowledge may be vital to prevent and treat post-operative chyle leakage.

[Importance of Virchow-Robin spaces]. / Bedeutung der Virchow-Robin-Räume.

Virchow-Robin spaces are perivascular fluid-filled cavities that surround perforating arteries and veins in the brain parenchyma. As a rule in healthy people they are approximately 5 mm in diameter. Typical localizations are brainstem ganglia, mesencephalon and the white matter of the brain. Morphological imaging characteristics of Virchow-Robin spaces are round or tubular, smoothly bordered areas which are hyperintense in T2-weighted sequences. Virchow-Robin spaces represent a physiological structure in normal brain parenchyma. It is assumed that they contain interstitial fluid filled with macrophages and play an important role in the drainage of interstitial fluid in the direction of the cervical lymph system. In many diseases, such as Alzheimer's disease, cerebrovascular diseases and traumatic brain injuries, an association with Virchow-Robin spaces is assumed. In the differential diagnostics lacunar infarcts, cystic space-occupying lesions, low-grade malignant tumors and arachnoid cysts must be considered. In individual studies an association with frequently occurring expanded perivascular spaces in patients with arterial hypertension and patients with CADASIL disease was established. Rarely, Virchow-Robin spaces are so expanded that they lead to compression of the aqueduct or the foramina of Monro with subsequent hydrocephalus.

Opportunities for Studying the Hydrodynamic Context for Breast Cancer Cell Spread Through Lymph Flow.

The lymphatic system serves as the primary route for the metastatic spread of breast cancer cells (BCCs). A scarcity of information exists with regard to the advection of BCCs in lymph flow and a fundamental understanding of the response of BCCs to the forces in the lymphatics needs to be established. This review summarizes the flow environment metastatic BCCs are exposed to in the lymphatics. Special attention is paid to the behavior of cells/particles in microflows in an attempt to elucidate the behavior of BCCs under lymph flow conditions (Reynolds number <1).

Lymph Node Metastases in Papillary and Medullary Thyroid Carcinoma Are Independent of Intratumoral Lymphatic Vessel Density.

BACKGROUND: Blood and lymph vessel invasion are well-recognized markers of tumor aggressiveness, as these are the routes that lead to metastases. Thyroid tumors, depending on the histological variant, tend to have distinctive biological behaviors and use different vascular routes to metastasize, yet the mechanisms underlying the metastatic process are still poorly understood. OBJECTIVES: The aim of this study was to assess how the lymph vessel density (LVD) in different histological types of thyroid tumors, and in their surrounding tissue, correlate with the presence of lymph node metastases (LNM) and tumor pathological features. METHODS: Lymph vessels of papillary thyroid carcinomas (PTC), of the classical (CVPTC, n = 50) and follicular variants (FVPTC, n = 18), and medullary thyroid carcinomas (MTC, n = 34) were immunohistochemically stained against antigen D2-40. The stained area was quantified using a computerized morphometric analysis tool and correlated with the tumor pathological characteristics. RESULTS: LVD within all analyzed thyroid tumor subtypes was significantly lower than in the surrounding thyroid tissues (p < 0.001). Despite intratumoral LVD being significantly higher in CVPTC than in FVPTC, and peritumoral LVD being significantly higher in MTC than in PTC (p < 0.05), no correlations were found between LVD (either intratumoral or peritumoral) and the presence of lymph node metastasis. CONCLUSIONS: As no LVD differences were found amongst thyroid tumors with or without LNM, dissemination is more likely to depend on the tumor ability to invade the abundant lymph vessel network of the surrounding thyroid tissue than on the ability of the tumor to promote de novo lymphangiogenesis.

Skin depigmentation along lymph vessels of the lower leg following local corticosteroid injection for interdigital neuroma.

Steroid injection is frequently used in the treatment of interdigital neuroma and has a high rate of success. We report the case of a patient who develops skin depigmentation at the injection site and linear streaks of depigmentation over the foot, the ankle and half way up to the knee after a steroid injection for interdigital neuroma. Minor disadvantages such as subcutaneous fat atrophy and depigmentation of the skin at the injection site are well known problems following steroid injection. Depigmentation of the skin with a lymphatic distribution in the foot after steroid injection for interdigital neuroma however, has not yet been reported before. This complication is a serious aesthetic problem and clinicians should be aware of this complication when treating patients with steroid injections for interdigital neuroma.

Lymph vessels: the forgotten second circulation in health and disease.

The lymphatic circulation is still a somewhat forgotten part of the circulatory system. Despite this, novel insights in lymph angiogenesis in health and disease, application of immune markers for lymphatic growth and differentiation and also the introduction of new imaging techniques to visualize the lymphatic circulation have improved our understanding of lymphatic function in both health and disease, especially in the last decade. These achievements yield better understanding of the various manifestations of lymph oedemas and malformations, and also the patterns of lymphovascular spread of cancers. Immune markers that recognize lymphatic endothelium antigens, such as podoplanin, LYVE-1 and Prox-1, can be successfully applied in diagnostic pathology and have revealed (at least partial) lymphatic differentiation in many types of vascular lesions.

Carcinoma inflamatório de mama ­ Uma abordagem comparada / Inflammatory mammary carcinoma - A comparative approach / Carcinoma inflamatório de mama - Un enfoque comparativo

O Carcinoma Inflamatório de Mama (CIM) é um neoplasma maligno de rápida evolução que apresenta baixa ocorrência tanto em cadelas quanto em mulheres. É pouco relatado pelos médicos veterinários no Brasil, fato que pode ser relacionado à falta de conhecimento da doença associado à necessidade da relação dos achados clínicos com exame histopatológico para o diagnóstico definitivo. Esse neoplasma também acomete a glândula mamária de mulheres, nas quais demonstra características clássicas de inflamação como dor, turgor de pele e aumento de temperatura local. Para diagnóstico definitivo é considerado a presença de êmbolos de células tumorais em canais linfáticos da derme associados aos sinais clínicos de inflamação. Devido ao grau de infiltração local, os sinais de inflamação e a presença de êmbolos em linfáticos, o paciente humano e veterinário apresentam prognóstico desfavorável. O CIM é pouco responsivo à quimioterapia e devido às características de inflamação, não apresenta indicação cirúrgica na maioria dos casos. Devido à agressividade do CIM em mulheres e nas cadelas, do prognóstico desfavorável e das restritas opções terapêuticas essa revisão objetiva descrever os avanços das opções terapêuticas além do tratamento paliativo na literatura atual além de apresentar uma abordagem comparada, considerando a cadela um modelo de estudo para a doença na mulher.

The Inflammatory Mammary Carcinoma (IMC) is a low-occurrence malignant neoplasm with rapid evolution that affects dogs and women. There are few reports of this disease in the Brazilian veterinary literature, which may be related to the lack of knowledge of the disease associated with the need of relating clinical findings to histopathology exams for definitive diagnosis. This neoplasm also affects the mammary glands in women, which demonstrates classical signs of inflammation such as pain, skin turgor and increased local temperature. The diagnosis considers the presence of tumor cell emboli in the lymph vessels in the dermis associated with clinical signs of inflammation. Due to the degree of local infiltration, signs of inflammation and the presence of lymph emboli, both human and veterinary patients have unfavorable prognosis. The IMC is poorly responsive to chemotherapy and due to its inflammation characteristics, in most cases, surgical removal is not recommended. Due to the aggressiveness of the IMC on women and bitches, poor prognosis and limited therapeutic options, this paper aims to describe the advances of therapeutic options beyond palliative care in current literature, as well as presenting a comparative approach considering the bitch as a study model for treating the disease in women.

El carcinoma inflamatorio de mama (CIM) es una neoplasia maligna de evolución rápida que tiene una baja incidencia tanto en perras como en mujeres. Es poco relatado por médicos veterinarios en Brasil, hecho que puede estar relacionado a la falta de conocimiento de la enfermedad, asociada a la necesidad de la relación de los hallazgos clínicos con examen histopatológico para el diagnóstico definitivo. Esta neoplasia también afecta a las glándulas mamarias de mujeres, lo que demuestra características clásicas de inflamación, como dolor, la turgencia de la piel y el aumento de la temperatura local. Para el diagnóstico definitivo se considera la presencia de émbolos de células tumorales en los canales dermis ganglios, asociados con los signos clínicos de inflamación. Debido al grado de infiltración local, los signos de inflamación y la presencia de embolias en el linfático, el paciente humano y veterinario presentan pronóstico desfavorable. El CIM es poco sensible a la quimioterapia y debido a las características de inflamación no presenta indicación quirúrgica en la mayoría de los casos. Debido a la agresividad del CIM en mujeres y perras, del pronóstico desfavorable y de las restrictas opciones terapéuticas, esa investigación tuvo como objetivo revisar el progreso de las opciones terapéuticas además del tratamiento paliativo en la literatura actual, allende presentar un enfoque comparativo, teniendo en cuenta que la perra es un modelo de estudios para la enfermedad en mujeres.

Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model.

Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that functions as a cell-surface sensor for coagulation factors and other proteases associated with the tumour microenvironment. Pancreatic cancer cells express high levels of PAR-2 and activation of PAR-2 may induce their proliferation and migration. Interestingly, however, PAR-2 expression is increased in stroma-rich pancreatic cancer regions, suggesting a potential role of PAR-2 in the tumour microenvironment. Here, we assessed the importance of PAR-2 in the stromal compartment by utilizing an orthotopic pancreatic cancer model, in which tumour cells are PAR-2-positive, whereas stromal cells are PAR-2-negative. We assessed tumour weight and volume and analysed proliferation and (lymph)angiogenesis both in vivo and in vitro. We show that genetic ablation of PAR-2 from the stromal compartment inhibits primary tumour growth, which is accompanied by reduced vascularization in primary tumours and reduced in tube formation of vascular endothelial cells in vitro. In contrast to smaller primary tumours, the number of lymph node metastases was increased in PAR-2-deficient animals, which was accompanied by an increased number of lymphatic vessels. In vitro tube-formation assays show that PAR-2 does not inhibit the intrinsic tube-forming capacity of lymphatic endothelial cells, but that PAR-2 actually inhibits cancer cell-induced tube formation. Overall, stromal PAR-2 thus plays a dual role in pancreatic cancer development by potentiating primary tumour growth but limiting lymphangiogenesis and subsequent lymph node metastasis. Our data identify a novel role of PAR-2 in the tumour microenvironment and pinpoint PAR-2 as a negative regulator of lymphangiogenesis.

Lymphangioma circumscriptum in an adult: an unusual oral presentation.

Lymphangioma is a benign hamartomatous tumor of lymphatic vessels. This lymphatic malformation is characterized by an abnormal proliferation of lymphatic vessels. Extra-oral lymphangiomas occur more frequently in the neck region predominantly in the posterior triangle, while intra-oral lymphangiomas are commonly seen in the tongue mainly on the dorsum surface. Various imaging modalities such as ultrasound and color Doppler are very useful in viewing the extent of the lesion. In most of the cases, surgical excision is the treatment of choice. The prognosis is good for most patients, but recurrence has also been reported in some cases, presumably because the lesion is interwoven between muscle fibers, preventing complete removal. This case report discusses the clinical features, color Doppler imaging, histopathology, and treatment of lymphangioma.

Oral lymphangioma - Case reports and review of literature.

Lymphangioma is a benign hamartomatous hyperplasia of lymphatic vessels. Majority of them are superficial, but a few may extend deeply into the connective tissue. Intraoral lymphangiomas occur more frequently on the dorsum of tongue, followed by palate, buccal mucosa, gingiva, and lips. Surgical excision is the treatment of choice. The prognosis is good for most patients, although large tumors of neck/tongue may result in airway obstruction and death. This case report series discusses the clinical features, histopathology, and treatment of lymphangioma.

Relationship between breast cancer-related lymphoedema and VEGF-C and VEGFR-3 / 中华普通外科杂志

Objective To study the distribution and clinicopathological characteristics between VEGF-C and pefitumoral lymph vessels density(PLVD) in breast cancer tissue, and to investigate the development and the mechanism of breast cancer-related lymphoedema (BCRL). Methods VEGF-C and VEGFR-3 were detected by using immunohistochemical technique for the detection of VEGF-C and its receptor VEGFR-3 in forty-seven breast cancer specimens. We measured the patients' circumferences of bilateral upper limbs to determine whether there was lymphoedema and made classification in the follow-ups. Results VEGF-C was positive in 33 out of 47 cases. PLVD significantly increased in VEGF-C positive groups (30.39±10. 46) than in negative groups (23.16±11.67) (P<0.05). VEGF-C semi-quantitative score was in a positive correlation with PLVD (r=0.334). The positive expression rate (42.55%) and semi-quantitative score (3.68±1.59) of VEGF-C increased in the lymph node positive group than in the negative group, PLVD increased in the lymph node positive group compared with that in negative group (32.12±10.29 vs. 24.82±11.06), P<0.05. The risk of lymphoedema increased in the VEGF-C negative group (5/14) compared with that in the positive group (3/33) (P<0.05). Conclusion VEGF-C has a high rate of positive expression in breast cancer, and is positively correlated with PLVD. High expression of VEGF-C can reduce the risk of BCRL in breast cancer.