PDGF—D和VEGF在宫颈鳞癌中的表达及其意义

目的：检测宫颈鳞癌组织中血小板源性生长因子D（PDGF—D）和血管内皮生长因子（VEGF）的表达,探讨二者在宫颈癌变过程中的作用及意义,为探讨宫颈鳞癌的发病机制和宫颈鳞癌的早期治疗提供理论依据。方法：采用免疫组织化学（sP法）检测40例宫颈鳞癌和10例正常宫颈组织中PDGF—D和VEGF蛋白的表达,分析两者之间的相关性及其与临床病理特征之间的关系。结果：宫颈鳞癌组织中PDGF—D和VEGF蛋白的表达显著高于正常宫颈组织（P〈0．05）;PDGF—D和VEGF的表达与宫颈鳞癌的分化程度及淋巴结转移有关（P〈0．05）;与年龄及临床分期无关（P〉0．05）。Spearman相关分析发现PDGF—D与VEGF表达程度呈正相关（r=0．346,P〈0．05）。结论：1．PDGF—D和VEGF在宫颈鳞癌组织中特异性高表达,可能在宫颈鳞癌的发生、发展与转移中起着重要作用。2．PDGF-D和VEGF表达与宫颈鳞癌的分化程度及淋巴结转移有关,与年龄及临床分期无关,提示它们可能在宫颈鳞癌的浸润和转移及预后方面有重要的监测意义。3．PDGF-D和VEGF在宫颈鳞癌组织中的表达呈正相关,提示两者起着相互促进的作用,对PDGF—D和VEGF的联合检查,为临床实际应用提供了参考。     

Bcl-2和COX-2在宫颈鳞癌中的表达及其临床意义

目的：观察Bcl-2和COX-2在正常宫颈和宫颈鳞癌中的表达情况,并探讨其与宫颈鳞癌发生发展的关系。方法：应用免疫组织化学s-P法检测40例宫颈鳞癌组织、10例正常宫颈组织中Bcl-2和COX-2的表达情况。结果：（1）Bcl-2在正常宫颈组织和宫颈鳞癌组织中的阳性表达率分别为30．0％、72．5％（P〈0．05）,而COX-2在正常宫颈组织和宫颈鳞癌组织中的阳性表达率分别为0．0％、60．0％（P〈0．05）。（2）在宫颈鳞癌中,Bcl-2的表达与宫颈鳞癌的病理分级、临床分期以及淋巴结转移无关（P〉0．05）,而COX-2的表达与宫颈鳞癌的病理分级及淋巴转移有关（P〈0．05）,与临床分期无关（P〉0．05）。（3）Spearman等级相关性分析显示宫颈鳞癌组织中Bcl-2和COX-2的表达呈正相关（r=0．517,P〈0．01）。结论：Bcl-2和COX-2在宫颈鳞癌中的表达升高并呈显著正相关,且COX-2的表达与宫颈鳞癌的淋巴转移有关,二者在宫颈癌的发生发展中可能起重要作用,有可能作为评估宫颈鳞癌淋巴结转移的参考指标。     

口腔鳞癌中D2-40表达的特点及临床意义

目的探讨口腔鳞癌组织中淋巴管分布、密度及其与临床病理因素之间的关系。方法应用免疫组化SP法检测口腔癌D2-40的表达情况,计数淋巴管密度（lymphatic vessel density,LVD）,分析其与临床病理特征间的关系。结果口腔鳞癌中的淋巴管形态及分布在不同区域具有异质性。与肿瘤中心（肿瘤实质）及癌旁正常组织比较,肿瘤边缘区（肿瘤间质）的淋巴管LVD为（11.09±2.958）,显著高于肿瘤中心（5.81±1.334）及癌旁正常组织（4.96±1.716）,且形态多呈扩张状态。结论口腔鳞癌中的淋巴管主要位于肿瘤边缘区,肿瘤边缘区LVD与淋巴结转移状态相关,检测口腔癌边缘区的LVD对预测是否发生淋巴结转移可能具有重要意义。     

Bcl-2 和COX-2 在宫颈鳞癌中的表达及其临床意义

目的：观察Bcl-2 和COX-2 在正常宫颈和宫颈鳞癌中的表达情况,并探讨其与宫颈鳞癌发生发展的关系。方法：应用免疫组 织化学S-P法检测40 例宫颈鳞癌组织、10 例正常宫颈组织中Bcl-2 和COX-2 的表达情况。结果：(1)Bcl-2 在正常宫颈组织和宫颈 鳞癌组织中的阳性表达率分别为30.0%、72.5 %(P<0.05),而COX-2在正常宫颈组织和宫颈鳞癌组织中的阳性表达率分别为0.0 %、 60.0 %(P<0.05)。(2)在宫颈鳞癌中,Bcl-2 的表达与宫颈鳞癌的病理分级、临床分期以及淋巴结转移无关(P>0.05),而COX-2 的表达 与宫颈鳞癌的病理分级及淋巴转移有关(P<0.05),与临床分期无关(P>0.05)。(3)Spearman 等级相关性分析显示宫颈鳞癌组织中 Bcl-2 和COX-2的表达呈正相关(r=0.517,P<0.01)。结论：Bcl-2 和COX-2 在宫颈鳞癌中的表达升高并呈显著正相关,且COX-2的 表达与宫颈鳞癌的淋巴转移有关,二者在宫颈癌的发生发展中可能起重要作用,有可能作为评估宫颈鳞癌淋巴结转移的参考指 标。     

胃癌组织中幽门螺杆菌L型感染与淋巴管形成关系的研究

目的 研究胃癌组织中D2-40、LYVE-1标记的微淋巴管密度(LVD)、血管内皮生长因子受体(VEGFR-3)表达与幽门螺杆菌L型(helicobacter pylori L-form,Hp-L型)感染之间的关系.方法 应用革兰染色和免疫组化SP法检测80例胃癌组织和25例对照组的Hp-L型感染,同时用免疫组化SP法检测上述组织的LVD值和VEGFR-3的表达,分析Hp-L型与LVD以及VEGFR-3表达的关系结果 胃癌组织中革兰染色L型检出阳性率为67.5％;免疫组化Hp-L型抗原表达阳性率为65％,两种方法检测同时阳性的病例50例,占62.5％.胃癌组的Hp-L型阳性率、LVD及VEGFR-3表达阳性率均高于对照组(P＜0.01);胃癌组中Hp-L阳性组的LVD值和VEGFR-3表达阳性率高于Hp-L阴性组.LVD与胃癌淋巴结转移具有一定关系.结论 Hp-L型感染与胃癌的发生、发展密切相关,Hp-L型可能是肿瘤淋巴管生成的重要促进因子,影响胃癌的侵袭和转移.     

甲状腺肿瘤组织VEGF-C和ERβ的表达与LVD的相关性分析

目的:探讨甲状腺肿瘤和癌旁正常甲状腺组织中VEGF-C和ERβ的表达与组织平均淋巴管密度的相关性.方法:采用SP免疫组织化学染色检测116例甲状腺癌、56例甲状腺腺瘤和20例正常甲状腺组织中VEGF-C和ERβ及D2-40的表达;以D2-40阳性结果计算组织平均淋巴管密度(LVD).观察不同甲状腺组织中VEGF-C和ERβ的表达水平并分析其与LVD的相关性.结果:甲状腺癌组织中VEGF-C的高表达阳性率显著高于正常甲状腺和甲状腺腺瘤(P＜0.05),ERβ的高表达阳性率显著低于正常甲状腺和甲状腺腺瘤(P＜0.05);两者表达呈轻度负相关(r=-0.312,P＜0.01);甲状腺癌VEGF-C表达与淋巴结转移和TNM分期有关(P＜0.01).用D2-40标记的LVD值在甲状腺癌、甲状腺腺瘤和正常甲状腺组织之间有显著性差异(P＜0.001).甲状腺癌中淋巴结转移组LVD显著高于无淋巴结转移组(P＜0.0001).VEGF-C表达与D2-40呈正相关(r=0.515,P＜0.01).结论:ERβ表达下调可能通过促进VEGF-C的表达,进而影响淋巴管增生,促进肿瘤淋巴道转移.     

PDGF-D和VEGF在宫颈鳞癌中的表达及其意义

目的:检测宫颈鳞癌组织中血小板源性生长因子D(PDGF-D)和血管内皮生长因子(VEGF)的表达,探讨二者在宫颈癌变过程中的作用及意义,为探讨宫颈鳞癌的发病机制和宫颈鳞癌的早期治疗提供理论依据。方法:采用免疫组织化学(SP法)检测40例宫颈鳞癌和10例正常宫颈组织中PDGF-D和VEGF蛋白的表达,分析两者之间的相关性及其与临床病理特征之间的关系。结果:宫颈鳞癌组织中PDGF-D和VEGF蛋白的表达显著高于正常宫颈组织(P0.05);PDGF-D和VEGF的表达与宫颈鳞癌的分化程度及淋巴结转移有关(P0.05);与年龄及临床分期无关(P0.05)。Spearman相关分析发现PDGF-D与VEGF表达程度呈正相关(r=0.346,P0.05)。结论:1.PDGF-D和VEGF在宫颈鳞癌组织中特异性高表达,可能在宫颈鳞癌的发生、发展与转移中起着重要作用。2.PDGF-D和VEGF表达与宫颈鳞癌的分化程度及淋巴结转移有关,与年龄及临床分期无关,提示它们可能在宫颈鳞癌的浸润和转移及预后方面有重要的监测意义。3.PDGF-D和VEGF在宫颈鳞癌组织中的表达呈正相关,提示两者起着相互促进的作用,对PDGF-D和VEGF的联合检查,为临床实际应用提供了参考。     

cFLIP在宫颈癌和宫颈上皮内瘤变组织中表达的意义

目的 研究cFLIP在宫颈癌和宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）组织中的表达及其临床意义。方法 应用SP免疫组化染色法检测40例宫颈癌,40例CIN和20例正常子宫颈组织中cFLIP的表达情况,并与病理类型、组织学分级、临床分期和是否有淋巴结转移等生物学行为进行相关分析。结果 宫颈癌、CIN及正常宫颈组织中cFLIP的表达阳性率分别为92．5％、70％和10％,三组间两两比较有显著性差异（P〈0．05）。CINⅠ级组与CINⅡ-Ⅲ级组及宫颈癌组比较有显著性差异（P〈0．05）,宫颈癌组与CINⅡ-Ⅲ级组比较差异无显著性（P〉0．05）。cFLIP表达阳性率与宫颈癌病理类型、组织学分级、淋巴结转移及临床分期无关。结论 cFLIP的特异性高表达是宫颈癌变的一个早期事件,可能在宫颈癌癌前病变向宫颈癌的发展过程中起重要作用。     

血管内皮生长因子-C与乳腺癌淋巴管生成和淋巴结转移的关系

目的探讨血管内皮生长因子-C与乳腺癌淋巴管生成和淋巴结转移的关系。方法免疫组化法检测21例乳腺增生组和68例乳腺浸润性导管癌组病灶组织内VEGF-C蛋白的表达,并用淋巴管内皮细胞特异性标志物D2-40标记肿瘤新生淋巴管,计数肿瘤淋巴管的密度（LVD）。结果乳腺浸润性导管癌组VEGF-C的表达和淋巴管的密度（LVD）都明显高于乳腺增生组（P〈0．01）;乳腺浸润性导管癌中VEGF-C阳性组中淋巴管的密度（11．32±5．78）与VEGF-C阴性组中的淋巴管密度（8．75±3．53）,差别有统计学意义（P〈0．01）;乳腺浸润性导管癌中VEGF-C蛋白的表达和淋巴管密度（LVD）都与有无腋窝淋巴结转移及淋巴结转移个数有关（P〈0．05）。结论VEGF-C在乳腺浸润性导管癌淋巴管的生成中起着重要的作用;VEGF-C的高表达和淋巴管密度（LVD）的升高是促进乳腺导管癌淋巴结转移的重要的影响因素。     

测定胰腺癌组织微血管密度及淋巴管密度的临床意义

目的:研究胰腺癌组织中微血管密度(Microvessel density,MVD)和淋巴管密度(Lymphatic vessel density,LVD)的变化、与胰腺癌临床病理的联系。方法:采用免疫组织化学SABC法应用CD34及D2-40分别检测41例胰腺导管腺癌患者配对癌组织内、癌旁及正常胰腺组织中MVD及LVD的表达情况,分析其与肿瘤分化程度、分期和淋巴转移间的相关性;以及癌组织MVD与癌旁组织LVD表达之间的关系。结果:在41例胰腺癌组织配对癌组织及正常胰腺组织平均MVD值分别为46.585±16.935,11.100±4.036,两组之间差别有统计学意义(P=0.000<0.01)。配对癌组织内、癌旁及正常胰腺组织中平均LVD值分别为11.244±4.800,15.829±7.470和13.512±5.139;其中癌旁组织与正常胰腺组织LVD值差别无统计学意义(P=0.060>0.05),癌旁组织与胰腺癌组织的LVD值有显著性差异(P=0.000<0.01)。癌组织内MVD值与癌旁组织LVD值之间有相关性(P=0.025<0.05)。结论:胰腺导管腺癌组织中MVD及LVD与肿瘤分化程度、病理分期及淋巴转移存在关联。胰腺癌组织内MVD值与癌旁组织LVD之间存在相关性。     

Clinical significance of peritumoral lymphatic vessel density and lymphatic vessel invasion detected by D2-40 immunostaining in FIGO Ib1-IIa squamous cell cervical cancer

The clinical significance of lymphangiogenesis in cervical cancer remains controversial. Our aim was to investigate the correlation between lymphangiogenesis, lymphatic vessel invasion (LVI) and tumor metastasis, invasion and prognosis in squamous cell cervical cancer. Paraffin sections of 90 patients with FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) Ib1-IIa squamous cell cervical cancer were stained for immunohistochemistry with a D2-40 monoclonal antibody against the carcinoembryonic antigen M2A. The lymphatic vessel density (LVD) and LVI were measured, and their relationship with the clinicopathological data was analyzed. D2-40-positive lymphatic vessels were found in 75 of the 90 patients (83.3 %). All D2-40-positive vessels were located in peritumoral areas. The mean±SD of the peritumoral LVD was 10.08±4.16. The positive rate of LVI was 32.0 % (24/75). The recurrence rate of patients with LVD >10 (62.1 %, 18/29) was significantly higher than that of patients with LVD ≤10 (34.8 %, 16/46, P = 0.021). The 5-year recurrence-free survival rate of patients with LVD >10 (41.0 %) was significantly lower than that of patients with LVD ≤10 (67.0 %, P = 0.045). Univariate analysis showed that the peritumoral LVD (≤10 vs >10) was correlated with LVI (absent vs present, P = 0.016). The peritumoral LVD and LVI showed no correlation with age, FIGO stage, tumor size, tumor grade, depth of invasion, or pelvic lymph node metastasis (all: P > 0.05). Peritumoral lymphangiogenesis was correlated with the recurrence and recurrence-free survival in patients with squamous cell cervical cancer. Examination of peritumoral LVD in these patients might therefore help to estimate the risk of recurrence.     

Prognostic Significance of Peritumoral Lymphatic Vessel Density and Vascular Endothelial Growth Factor Receptor 3 in Invasive Squamous Cell Cervical Cancer

Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic metastasis is associated with a poor prognosis. In patients who have undergone a radical hysterectomy, lymphovascular space invasion (LVSI), assessed on hematoxylin and eosin-stained slides, is a major factor for adjuvant therapy in patients with cervical cancer. With the advent of a lymphatic endothelial cell-specific marker, such as D2-40, it is now possible to distinguish between blood and lymphatic space invasion (LSI). In this study, the utility of D2-40 was assessed for the detection of lymphatic vessel density (LVD) and identification of LSI. The expressions of vascular endothelial growth factor receptor-3 (VEGFR-3), VEGF-C, tyrosine receptor kinase-2, and angiopoietin-1 were assessed by immunohistochemical methods on 50 patients with squamous cell carcinoma of the cervix. Clinicopathologic characteristics, including pelvic lymph node metastasis, were correlated with the above histochemical findings. We found that lymphangiogenesis, measured by an increase in peritumoral LVD, was significantly associated with positive lymph node status (P < .005). VEGFR-3 expression was significantly associated with LVD (P < .05). D2-40 staining verified LSI (P = .03) and surpassed that of hematoxylin and eosin-identified LVSI (P = .54). In conclusion, lymphangiogenic markers, specifically LVD quantified by D2-40 and VEGFR-3, are independently associated with LSI and lymph node metastasis in patients with early squamous cell carcinoma of the cervix treated with radical hysterectomy and pelvic lymphadenectomy.     

VEGF-D的表达与膀胱移行细胞癌LVD及淋巴结转移有关

目的观察血管内皮生长因子D(vascular endothelial growth factor D,VEGF-D)在人膀胱移行细胞癌组织内的表达,探讨VEGF-D在膀胱移行细胞癌组织淋巴管密度(lymphatic vessel density,LVD)及淋巴结转移之间的关系。方法取人膀胱移行细胞癌组织蜡块30例,免疫组化法观察VEGF-D在膀胱移行细胞癌组织内的表达情况。以淋巴管内皮特异性标记物D2-40标记淋巴管,计数癌组织内淋巴管密度。结果VEGF-D蛋白主要表达于癌细胞胞浆内,VEGF-D在淋巴结转移组膀胱移行细胞癌组织内的表达水平明显高于无淋巴结转移组(P0.05);淋巴结转移组膀胱移行细胞癌组织内的淋巴管密度明显高于无淋巴结转移组(P0.05)。VEGF-D表达与膀胱移行细胞癌淋巴管密度及淋巴结转移之间具有显著的相关性。结论VEGF-D表达在膀胱移行细胞癌组织内淋巴管生成及淋巴结转移中起重要作用。     

Lymphatic microvessel density as a prognostic factor in non-small cell lung carcinoma: a meta-analysis of the literature

The role of lymphatic microvessel density (LVD) as a prognostic factor for survival of patients with non-small cell lung carcinoma (NSCLC) remains controversial. To evaluate this potential role, we performed a systematic review of the electronic databases PubMed and EMBASE for relevant literature to review and compile available survival results. To be eligible, a study had to assess LVD in patients with NSCLC and to compare survival based on LVD stratification. Among 12 eligible trials, all dealt with NSCLC, and 10 trials provided results for the meta-analysis of survival data (evaluable trials). In terms of survival, high LVD was reported to be an unfavorable prognostic factor for overall survival in 8 studies, whereas it was not in 4 studies. The overall survival hazard ratio for the 10 evaluable studies (1,426 patients) was calculated to be 1.41 (95% CI: 1.14–1.75) using a random effects model, indicating a poorer survival for NSCLC patients with high LVD. The hazard ratio was 1.52 (95% CI: 1.10–2.11) in 5 NSCLC studies where LVD was assessed based on D2-40 and 1.31 (95% CI: 1.08–1.60) in 4 studies where LVD was measured based on vascular endothelial growth factor receptor-3. This study supports the hypothesis that the lymphatic microvessel count or LVD, which reflects levels of lymphangiogenesis, is a poor prognostic factor for patient survival in surgically treated NSCLC. However, the present findings may overestimate the prognostic capacity of LVD because of publication and report bias. In addition, the standardization of lymphangiogenesis assessment by the lymphatic microvessel count is necessary.     

Does Immunohistochemistry Allow Easy Detection of Lymphatics in the Optic Nerve Sheath?

We evaluated the validity of anti-D2-40 and anti-LYVE-1 (antibodies against lymphatic endothelium) for IHC diagnosis and semiquantification of lymphatic vessels in the dura mater of the intraorbital portion of the human optic nerve (ON). Fourteen specimens were analyzed using light microscopy within 12 hr postmortem. We found in all specimens that both D2-40 and LYVE-1 stained lymphatic vessels as well as venules and arterioles. Our findings show lymphatic vessels in the meninges of the intraorbital portion of the human ON. Anti-D2-40 and anti-LYVE-1 antibodies, however, are not found to be exclusively specific to the endothelial layer of lymphatics because they also stain the endothelial layer of venules and arterioles. For the unequivocal identification of lymphatics, additional morphological criteria are necessary. Nevertheless, D2-40 and LYVE-1 staining allows rapid identification of endothelial layers. (J Histochem Cytochem 56:1087–1092, 2008)     

How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis?

Background

Lymphatic vessels are major routes for metastasis in head and neck squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a molecule expressed in LECs, however, the potential prognostic usefulness of this molecule is not completely understood in HNSCC. We aimed to investigate the value of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as prognostic marker for HNSCC.

Methods

Thirty-one cases of HNSCC were stained for D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting positive reactions in 10 hotspot areas at ×200 magnification.

Results

D2-40 was specific for lymphatic vessels and did not stain blood vascular endothelial cells. LECs showed more tortuous and disorganized structure in intratumoral lymphatic vessels than in peritumoral ones. No statistical differences were observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD and intratumoral-BVD. Tumor D2-40 staining was positively associated with lymphatic vessel invasion (p = 0.011).

Conclusion

LVD is a powerful marker for HNSCC prognosis. We found significant differences in peritumoral and intratumoral D2-40 immunoreactivity, which could have important implications in future therapeutic strategies and outcome evaluation.

     

Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients

ABSTRACT: BACKGROUND: Mounting clinical and experimental data suggest that the migration of tumor cells into lymph nodes is greatly facilitated by lymphangiogenesis. Vascular endothelial growth factor (VEGF)-C and D have been identified as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis. The purpose of this study was to investigate the location of lymphangiogenesis driven by tumor-derived VEGF-C/D in breast cancer, and to determine the role of intratumoral and peritumoral lymphatic vessel density (LVD) in lymphangiogenesis in breast cancer. METHODS: The expression levels of VEGF-C/D were determined by immunohistochemistry, and intratumoral LVD and peritumoral LVD were assessed using immunohistochemistry and the D2-40 antibody in 73 patients with primary breast cancer. The associations of intratumoral LVD and peritumoral LVD with VEGF-C/D expression, clinicopathological features and prognosis were assessed. RESULTS: VEGF-C and D expression were significantly higher in breast cancer than benign disease (P < 0.01). VEGF-C (P < 0.001) and VEGF-D (P = 0.005) expression were significantly associated with peritumoral LVD, but not intratumoral LVD. Intratumoral LVD was associated with tumor size (P = 0.01). Peritumoral LVD was significantly associated with lymph node metastasis (LNM; P = 0.005), lymphatic vessel invasion (LVI; P = 0.017) and late tumor,node,metastasis(TNM) stage (P = 0.011). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, overall survival and disease-free survival in multivariate analysis. CONCLUSIONS: This study suggests that tumor-derived VEGF-C/D induce peritumoral lymphangiogenesis, which may be one mechanism that leads to lymphatic invasion and metastatic spread. Peritumoral LVD has potential as an independent prognostic factor in breast cancer patients.     

Lymphatic microvessel density and vascular endothelial growth factor-C and -D as prognostic factors in breast cancer: a systematic review and meta-analysis of the literature

The use of lymphatic microvessel density (LVD) and pro-lymphangiogenic mediators as prognostic factors for survival in breast cancer remains controversial. We searched the electronic databases PubMed and EMBASE without language restrictions for relevant literature to aggregate the survival results. To be eligible, every study had to include the assessment of the LVD or the expression of vascular endothelial growth factor (VEGF)-C or -D in patients with breast cancer and provide a survival comparison, including disease-free survival (DFS) or overall survival (OS), according to the LVD, VEGF-C or VEGF-D status. Across all studies, 56.64?% of patients were considered to have a VEGF-C-positive tumor, and 65.54?% of patients had VEGF-D-positive tumors. High LVD had an unfavorable impact on DFS, with a pooled hazard ratio (HR) of 2.222 (95?% CI 1.579–3.126) and an OS with a HR of 2.493 (95?% CI 1.183–5.25). According to the different lymphatic makers, the subgroup HR in the D2-40 studies was 2.431 (95?%?CI 1.622–3.644) for DFS and 4.085 (95?% CI 1.896–8.799) for OS. VEGF-C overexpression, as assessed by immunochemistry, was a prognostic factor for decreased DFS (HR 2.164; 95?% CI 1.256–3.729) and for decreased OS (HR 2.613; 95?% CI 1.637–4.170). VEGF-D overexpression was a significant although weak prognostic factor for DFS only when assessed by immunochemistry, with a HR of 2.108 (95?% CI 1.014–4.384). Our meta-analysis demonstrated that LVD, VEGF-C and VEGF-D could predict poor prognosis in patients with breast cancer. However, standardization of the assessment of LVD and for the expression of lymphangiogenesis factors is needed.