膀胱癌VEGF-C的表达与局部淋巴结内淋巴管生成之间的关系

目的观察血管内皮生长因子(VEGF)-C在膀胱癌组织内的表达情况,分析VEGF-C的表达与膀胱癌局部淋巴结内淋巴管生成及淋巴结转移之间的关系。方法取膀胱癌病例60例,其中,有淋巴结转移组26例及转移淋巴结30例,无淋巴结转移组34例及淋巴结48例。应用免疫组化法和Western blot技术检测VEGF-C在膀胱癌组织及转移淋巴结内的表达。以D2-40作为淋巴管内皮特异性标记物,检测膀胱癌局部淋巴结内淋巴管生成情况。结果 VEGF-C主要表达于膀胱癌细胞胞浆内及癌组织周围浸润的炎性细胞,在有淋巴结转移的膀胱癌组织中的表达量高于其在无淋巴结转移的膀胱癌组织内的表达量。30例有转移的淋巴结内VEGF-C的表达均呈阳性,并见大量新生的淋巴管,淋巴管腔内可见入侵的肿瘤细胞。在无淋巴结转移组病例中,膀胱癌组织VEGF-C阳性者局部淋巴结内淋巴管密度明显高于VEGF-C阴性者淋巴结内淋巴管密度。结论 VEGF-C的表达与膀胱癌淋巴结转移及淋巴管生成密切相关。     

VEGF-C表达与胰腺癌淋巴结转移及预后的关系

目的 观察血管内皮生长因子(VEGF)-C在胰腺癌组织内的表达情况,分析VEGF-C的表达与胰腺癌淋巴结转移和预后之间的关系。方法 取胰腺癌病例52例,其中,伴淋巴结转移组36例,无淋巴结转移组16例。应用免疫组化法和Western blot技术观察VEGF-C在胰腺癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,观察胰腺癌组织内淋巴管生成的情况。采用Kaplan-Meier法绘制生存曲线判断VEGF-C的表达对胰腺癌预后的影响。结果 Western blot和免疫组化法检测结果表明,VEGF-C主要表达于胰腺癌细胞浆内,淋巴结转移组阳性表达量明显高于无淋巴结转移组(p<0.05)。D2-40表达于胰腺癌组织内淋巴管内皮细胞,VEGF-C阳性组淋巴管数密度明显高于VEGF-C阴性组(p<0.05),表明VEGF-C的表达与胰腺癌淋巴管生成密切相关。Kaplan-Meier生存分析表明VEGF-C表达阴性患者的生存率均高于VEGF-C表达阳性患者,VEGF-C的表达影响患者的预后。结论 VEGF-C在胰腺癌的淋巴管生成和淋巴结转移过程中发挥重要作用,VEGF-C的表达是影响胰腺癌患者预后的主要因素之一。     

Smad4和VEGF-C在喉癌中的表达及其与淋巴管生成之间的关系

目的观察Smad4与VEGF-C在喉癌组织内的表达情况,分析Smad4和VEGF-C的表达与喉癌组织内淋巴管生成及淋巴结转移之间的关系。方法取喉癌病例58例,其中淋巴结转移组34例,无淋巴结转移组24例。应用免疫组化法和Western blot技术观察Smad4和VEGF-C在喉癌组织内的表达。以D2-40特异性标检测喉癌组织内淋巴管生成情况。结果 Smad4在无淋巴结转移的喉癌组织内的表达率明显高于其在有淋巴结转移组的表达率。Smad4表达阳性组的淋巴管数密度(LVD)明显低于Smad4表达阴性组的LVD。VEGF-C在淋巴结转移组的表达率明显高于其在无淋巴结转移组的表达率。Smad4的表达与VEGF-C的表达呈显著的负相关性(r=-0.391)。结论 VEGF-C在喉癌淋巴管的发生及淋巴结转移中发挥重要作用。Smad4与VEGF-C的表达呈负相关,Smad4可能有抑制喉癌淋巴管生成和淋巴道转移的作用。     

肿瘤淋巴结转移机制的研究进展

淋巴转移是肿瘤最常见及最基本的转移途径 ,也是肿瘤患者致死的主要原因 ,在肿瘤淋巴转移过程中 ,新生淋巴管的形成是其必要条件 ,血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)家族的发现 ,使得对肿瘤淋巴管生成的分子机制有了深入了解 ,本文综述近年肿瘤淋巴转移机制及治疗策略中的相关研究进展 ,简述笔者所从事电穿孔治疗中针对淋巴转移的研究设想。     

VEGF-C和Smad4在结肠癌淋巴管生成和淋巴道转移中的作用

目的研究血管内皮生长因子C(VEGF-C)和Smad4对结肠癌淋巴管生成、淋巴结转移的影响。方法应用免疫组化方法检测79例人结肠癌组织中VEGF-C、VEGFR-3、TGF-β1、TβR-Ⅱ和Smad4的表达和淋巴管密度(LVD)。结果 LVD与VEGF-C表达水平呈正相关、与Smad4表达呈负相关;有淋巴结转移的人结肠癌组织VEGF-C表达水平高于无淋巴结转移者(<0.001)、Smad4表达低于无淋巴结转移者(=0.001);VEGF-C表达与Smad4表达呈负相关(<0.001,R=-0.507)。结论在结肠癌组织中VEGF-C和Smad4与淋巴管生成、淋巴道转移相关。     

肿瘤淋巴管生成与肿瘤转移研究进展

现已证实淋巴管是肿瘤细胞转移播散至局部淋巴结的主要通路。但关于淋巴管发生的分子机制却了解甚少。新近研究证明血管内皮生长因子(VEGF)-C和VEGF-D及其受体VEGFR-3信号通路是淋巴管形成的基础,并在转基因动物模型观察到VEGF-C和VEGF-D可诱导肿瘤淋巴管生成,并促进其淋巴结转移。然而,VEGF-C和-D如何调节肿瘤相关淋巴管生成,对于肿瘤细胞如何从原发肿瘤逃逸,并怎样进入淋巴管,目前仍不清楚。为此,现就近期淋巴管生成与肿瘤转移研究进展作一简要综述。     

Smad4的表达与卵巢癌淋巴管生成及淋巴结转移之间的关系

目的观察Smad4和血管内皮生长因子(VEGF)-C在卵巢癌组织内的表达情况,分析Smad4和VEGF-C的表达与卵巢癌淋巴管生成及淋巴结转移之间的关系。方法取卵巢癌病例60例,其中,淋巴结转移组36例,无淋巴结转移组24例。应用免疫组化法和Westernblot技术观察Smad4和VEGF-C在卵巢癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,检测卵巢癌组织内淋巴管生成情况。结果 Smad4表达于卵巢癌细胞胞浆和胞核内,其在无淋巴结转移组的表达率明显高于其在有淋巴结转移组的表达率。Smad4表达阳性组的淋巴管数密度(LVD)明显低于Smad4表达阴性组的LVD。VEGF-C主要表达于卵巢癌细胞胞浆内,其在淋巴结转移组的表达率明显高于其在无淋巴结转移组的表达率。Smad4的表达与VEGF-C的表达呈显著的负相关性。Western blot检测结果表明,VEGF-C蛋白在有淋巴结转移卵巢癌组织中的表达量高于其在无淋巴结转移卵巢癌组织内的表达量,而Smad4在有淋巴结转移卵巢癌组织内的表达量明显低于其在无淋巴结转移组的表达量。结论 Smad4与VEGF-C的表达呈负相关,Smad4可能通过调节VEGF-C蛋白的表达而抑制卵巢癌淋巴管生成和淋巴道转移。     

喉癌中VEGF-C的表达与淋巴管生成及预后关系的研究

目的研究血管内皮生长因子-C(vessel endothelium growth factor C,VEGF-C)在喉癌组织的表达与临床病理特征的关系,探讨VEGF-C与喉癌淋巴管生成及预后的关系。方法以45例经病理确诊的喉癌组织为实验组,以20例喉良性病变组织为对照组,采用免疫组化SP法对上述组织中VEGF-C蛋白的表达进行分析,同时采用5′-核苷酸酶-碱性磷酸酶双重染色法(5′-Nase-ALP)计数淋巴管密度(LVD),并结合临床病理特征和生存资料进行相关分析。结果①在喉癌组织中VEGF-C的阳性率为37.8%,明显高于在正常喉组织内的表达水平(P<0.05);②VEGF-C表达与瘤内和瘤周LVD、淋巴结转移、淋巴管浸润显著相关(P<0.05),而与年龄、性别、肿瘤部位及组织学分级无关(P>0.05);③Kaplan-Meier生存曲线分析表明VEGF-C的表达与生存率呈负相关(P<0.05)。结论 VEGF-C促进喉癌淋巴管生成和转移,VEGF-C可以成为判断喉癌预后的生物学指标之一。     

趋化因子受体CCR7的表达与卵巢癌淋巴管入侵及淋巴结转移的关系

目的 观察趋化因子受体CCR7在卵巢癌组织内的表达情况,分析CCR7的表达与肿瘤淋巴管入侵和淋巴结转移之间的关系。方法 取临床资料完整的卵巢癌病例64例,其中,淋巴结转移组40例,无淋巴结转移组24例。应用免疫组化法和Western blot技术观察CCR7在卵巢癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,观察卵巢癌组织内肿瘤淋巴管入侵的情况。结果 免疫组化法和Western blot检测结果表明,CCR7表达于卵巢癌细胞浆和胞膜内,有淋巴结转移组的表达量明显高于无淋巴结转移组(p<0.05)。D2-40表达于卵巢癌组织内淋巴管内皮细胞,肿瘤淋巴管入侵在CCR7阳性组的发生率明显高于CCR7阴性组的发生率,CCR7表达与肿瘤淋巴管入侵发生率有显著相关性(p<0.05)。结论 CCR7的表达与卵巢癌发生肿瘤淋巴管入侵和淋巴结转移密切相关,提示CCR7在卵巢癌淋巴结转移中可能起重要作用。     

VEGF-C表达和微淋巴管密度与胃癌淋巴转移的关系及意义

目的探讨胃癌组织血管内皮生长因子C(VEGF-C)表达和微淋巴管密度(MLVD)及两者与胃癌淋巴转移的关系。方法应用免疫组织化学方法检测208例人胃癌组织、40例癌浸润前缘组织及139例人胃正常粘膜组织中VEGF-C、D2-40的表达,对D2-40阳性脉管进行MLVD计数,并结合病理资料进行统计学分析。结果胃癌组织VEGF-C的表达明显高于正常胃粘膜组织(χ2=109.199,P<0.01);胃癌组织中有淋巴结转移(χ2=14.496,P<0.01)或浸润透浆膜(χ2=11.586,P<0.01)组VEGF-C表达水平分别较无转移或浸润未及浆膜组增高。癌浸润前缘组织中MLVD(18.36±15.60个/mm2)明显高于胃癌组(9.41±9.32个/mm2,t=-3.681,P<0.01)和胃正常粘膜组织(7.70±7.69个/mm2,t=-4.180,P<0.01);胃癌淋巴结转移组MLVD(9.81±9.97个/mm2)高于无转移组(6.41±7.85个/mm2,t=2.516,P<0.01),而在浸润透浆膜组(11.20±10.55个/mm2)和未及浆膜组(8.54±9.36个/mm2)MLVD无差别(t=1.467,P=0.472)。另外,在胃癌组织中VEGF-C表达与MLVD呈正相关(F=2.910,P<0.05)。结论VEGF-C在胃癌中的高表达与胃癌浸润深度、淋巴转移密切相关。     

乳腺癌中Syk、VEGF-C表达与淋巴结转移的关系

目的研究乳腺癌组织中Syk、VEGF-C的表达与淋巴结转移的关系。方法分别采用免疫组织化学EnVision两步法及SP法检测55例乳腺癌组织中Syk、NFκB(p65)及VEGF-C的表达情况。结果55例乳腺癌组织中,Syk、VEGF-C及p65阳性率分别为50.9%,56.4%,81.8%。Syk在淋巴结转移组的表达低于无淋巴结转移组(P0.05);VEGF-C在淋巴结转移组的表达高于无淋巴结转移组(P0.05);p65在两组之间的表达差异无显著性(P0.75),p65胞核移位率在淋巴结转移组高于无淋巴结转移组(P0.025)。随着Syk表达增强VEGF-C的表达减弱,二者呈负相关(r=-0.620,P=0.000);p65胞核移位与Syk的表达强度降低有关(r=0.448,P=0.002),而与VEGF-C的表达强度增高有关(r=0.310,P=0.036)。结论乳腺癌中,Syk可能通过抑制NFκB的活性而下调VEGF-C的表达,从而抑制乳腺癌的淋巴结转移。     

Comparison of molecular determinants of angiogenesis and lymphangiogenesis in lymph node metastases and in primary tumours of patients with breast cancer

Angiogenesis and lymphangiogenesis are complex processes, driven by multiple factors. In primary breast tumours (PTs), VEGFA, -C and -D are the most important (lymph)angiogenic factors. The induction of lymphangiogenesis in axillary lymph node (LN) metastases of patients with breast cancer was described recently. To compare the molecular determinants of (lymph)angiogenesis in LN metastases and PTs of breast cancer patients, RNA was isolated from formalin-fixed, paraffin-embedded tissue sections of a metastatically involved and uninvolved LN and the PT from 26 lymph node-positive patients. The expression of 12 (lymph)angiogenic markers was measured by qRT-PCR. Expression was correlated with tumour cell proliferation, angiogenesis and lymphangiogenesis, quantified by tumour cell proliferation fraction (TCP%) and (lymphatic) endothelial cell proliferation fraction [(L)ECP%]. TCP%, ECP% and LECP% were assessed on immunohistochemical double stains for CD34/Ki-67 and D2-40/Ki-67, respectively. In involved LNs, the relative gene expression levels of PROX1 (p < 0.001) and FGF2 (p = 0.008) were decreased and the expression levels of VEGFA (p = 0.01) and PDGFB (p = 0.002) were increased compared to uninvolved LNs. The expression of most markers was increased in PTs compared to involved LNs. In metastatically involved LNs, the expression of VEGFA correlated with ECP% (r = 0.54, p = 0.009) and LECP% (r = 0.76, p < 0.001). In PTs, VEGFA correlated only with ECP% (r = 0.74, p < 0.001). VEGFD correlated with peritumoural LECP% (r = 0.61, p = 0.001) and with VEGFC (r = 0.78, p < 0.001). Linear regression analysis confirmed the expression of VEGFA as an independent predictor of ECP% in both PTs and LN metastases and of LECP% in LN metastases. The expression of VEGFD, but not of VEGFA, independently predicted peritumoural LECP% in PTs. Our results confirm existing data that, in PTs, angiogenesis and lymphangiogenesis are respectively driven by VEGFA and VEGFD. In contrast, in LN metastases, both processes seem to be driven by VEGFA. Lymphangiogenesis in PTs and in LN metastases might thus be driven by different factors.     

血管内皮生长因子C和趋化因子受体CCR7的表达与膀胱癌淋巴结转移之间的关系

目的观察血管内皮生长因子(VEGF)-C和趋化因子受体CCR7在膀胱移行细胞癌组织内的表达情况,分析VEGF-C和CCR7表达与癌淋巴结转移之间的关系。方法取膀胱癌病例60例,其中,淋巴结转移组36例,无淋巴结转移组24例。应用免疫组化法和Western blot技术观察VEGF-C和CCR7在膀胱癌组织内的表达。结果 VEGF-C和CCR7主要表达于膀胱癌细胞胞浆或/和胞膜内,二者在淋巴结转移组的表达率明显高于无淋巴结转移组。VEGF-C和CCR7蛋白同时表达在淋巴结转移组和非淋巴结转移组中的表达率分别为61.1%和33.3%,VEGF-C和CCR7的表达具有显著的相关性,联合检测VEGF-C和CCR7诊断膀胱癌淋巴结转移具有较高的准确度,ROC曲线下面积达0.708。结论 VEGF-C和CCR7在促进膀胱癌淋巴结转移中可能具有一定的协同作用,二者联合检测有助于膀胱癌淋巴结转移的早期诊断     

Intussusceptive lymphangiogenesis in vascular transformation of lymph node sinuses

Numerous lymphatic anastomosing channels in the lymph nodes are the most demonstrative finding of the rare lesion termed “vascular transformation of lymph node sinuses” (VTS). The mechanism of lymphatic vessel formation in VTS has not been studied. Vessel intussusception contributes to vascular expansion, and intraluminal pillars/posts, interstitial tissue structures or larger pillars (ITSs) and folds are the hallmarks of this process in blood vessels. The aim of this work is to assess whether these hallmarks of intussusception occur in VTS lymphatic vessels, indicating intussusceptive lymphangiogenesis. For this purpose, specimens of five cases of VTS were used for serial histological sections, immunohistochemistry and immunofluorescence in confocal microscopy, which enabled us to demonstrate the 3D image that defines the pillars. The studies showed a) meshworks of lymphatic vessels, which form complex loops, resembling sinuses of lymph nodes, b) presence of intralymphatic pillars, ITSs and folds, with a cover of lymphatic endothelial cells expressing podoplanin and a varying-sized connective core (e.g. collagen), and c) increase of vessel meshwork and linear arrangement, splitting and fusion of ITSs, pillars and folds, with remodelling and segmentation. In conclusion, the development of lymphatic vessel loops, ITSs, pillars and folds with segmentation in VTS supports intussusceptive lymphangiogenesis. This mechanism of intussusception is of interest because it participates in VTS histogenesis, contributes to general knowledge of intussusceptive lymphangiogenesis, which has received less attention than intussusception in blood vessels, and provides a basis for further studies in other lymphatic conditions.     

喉癌中胶原和钙结合EGF域1的表达与VEGF-C和淋巴管生成及预后的关系

目的 探讨胶原和钙结合EGF域1(Ccbe1)在喉癌组织中的表达及其与血管内皮生长因子-C(VEGF-C)、淋巴管生成及预后的相关性.方法 以45例经病理确诊的喉癌组织为实验组,20例喉良性病变组织为对照组,采用免疫组织化学法和Western bolt法对上述组织中Ccbe1和VEGF-C蛋白的表达进行分析,同时应用LYVE-1免疫组化染色计数淋巴管密度(LVD),并结合临床病理特征和生存资料进行相关分析.结果 喉癌组织中Ccbe1和VEGF-C的蛋白表达均高于良性病变组织(P＜0.05),且Ccbe1和VEGF-C的表达具有相关性(r=0.338,P＜0.05);在喉癌组织中Ccbe1的表达与 LVD、淋巴结转移和TNM临床分期密切相关(P＜0.05),Ccbe1阳性表达与生存率负相关(p＜0.05).结论 Ccbe1能够促进喉癌淋巴管生成,其机制可能语 上调VEGF-C表达有关,检测Ccbe1表达可成为判断喉癌预后新的生物学指标.     

Methylene blue-assisted lymph node dissection in combination with ex vivo sentinel lymph node mapping in gastric cancer

Aims:  Lymph node (LN) stage is still the strongest prognostic marker in potentially curable gastric cancer. Accuracy of histopathological lymph node assessment depends on the number of investigated LNs and detection rate of metastases and micrometastases. The aim was to perform a feasibility study employing intra-arterial methylene blue injection – a novel method to improve LN harvest – and ex vivo sentinel LN mapping.
Methods and results:  A total of 33 cases were enrolled, including 14 retrospective cases that served as a control group. The methylene group showed a highly significant improved mean LN harvest compared with unstained cases, with 38 ± 14 versus 21 ± 10 LNs ( P  < 0.001), respectively. The detection rate of ex vivo sentinel mapping was 88%. No skip metastases occurred.
Conclusion:  Both techniques have the potential to improve the accuracy of histopathological LN staging and can be combined successfully.     

乳腺癌前哨淋巴结活检术中不同染色淋巴结与肿瘤转移的关系

目的探讨乳腺癌前哨淋巴结活检术(SLNB)中不同染色情况的淋巴结与肿瘤转移的关系。方法选择我院2014年1月至2018年1月行前哨淋巴结活检的乳腺癌患者92例,以亚甲蓝为示踪剂,根据92例乳腺癌患者SLNB中淋巴结染色情况的不同分为无染色组、完全染色组和染色不均组,病理检测3组患者淋巴结的肿瘤转移情况并作比较。结果92例乳腺癌SLNB共取得淋巴结256枚,平均每例患者2.8枚,无染色组(80枚)肿瘤转移率为13.8%,完全染色组(112枚)肿瘤转移率为43.8%,染色不均组(64枚)肿瘤转移率为62.5%,3组间肿瘤转移率差异有统计学意义(P<0.05)。结论乳腺癌SLNB中染色不均的淋巴结最易出现肿瘤转移,其次为完全染色的淋巴结,染色淋巴结附近看到的未染色淋巴结也有肿瘤转移的可能,宜一并切除送检,有利于降低假阴性率。