血管内皮生长因子C及其受体3在人恶性黑色素瘤组织内的表达及意义

目的 观察人恶性黑色素瘤组织内血管内皮生长因子C(VEGF-C)及其受体3(VEGFR-3)的表达,探讨VEGF-C和VEGFR-3在恶性黑色素瘤淋巴管生成及淋巴道转移中的作用.方法 取人恶性黑色素瘤组织48例(石蜡标本30例,术后新鲜组织18例),应用免疫组织化学和RT-PCR技术,观察VEGF-C和VEGFR-3蛋白及mRNA在恶性黑色素瘤组织内的表达情况.以淋巴管内皮透明质酸受体(LYVE-1)标记淋巴管,计数恶性黑色素瘤组织淋巴管数密度.结果 VEGF-C和VEGFR-3蛋白主要表达于恶性黑色素瘤细胞胞浆内,在肿瘤周围的血管和淋巴管内皮上也可见VEGFR-3蛋白表达,VEGF-C和VEGFR-3蛋白在淋巴结转移组恶性黑色素瘤组织内的表达水平明显高于无淋巴结转移组(P<0.05).在18例新鲜恶性黑色素瘤中,淋巴结转移组VEGF-C和VEGFR-3mRNA的表达明显高于无淋巴结转移组(P<0.01).LYVE-1表达于肿瘤间质内的淋巴管内皮细胞,淋巴结转移组恶性黑色素瘤组织中的淋巴管数密度(LMVD)为9.845±2.454,无淋巴结转移组恶性黑色素瘤组织中的淋巴管数密度为6.534±2.193,淋巴结转移组恶性黑色素瘤组织内的淋巴管数密度明显高于无淋巴结转移组(P<0.01).结论恶性黑色素瘤组织内VEGF-C表达明显增高,并通过上调其受体VEGFR-3的表达促进恶性黑色素瘤组织内淋巴管的生成,从而促进恶性黑色素瘤的淋巴道转移.     

塞来昔布对小鼠移植瘤生长及淋巴管生成的影响

目的观察塞来昔布(Celecoxib)对小鼠移植瘤生长、COX-2、VEGF-C表达和淋巴管生成影响,探讨抑制肿瘤淋巴转移的机制。方法构建S180小鼠移植瘤模型,应用大体观察、HE染色、免疫组化和Western blot,比较对照组和Celecoxib给药组荷瘤鼠肿瘤生长、COX-2、VEGF-C表达和淋巴管分布。结果 Celecoxib组与对照组相比瘤体生长缓慢,第8周时肿瘤体积明显比对照组小,COX-2和VEGF-C的表达均下调,淋巴管密度降低。结论 Celecoxib抑制肿瘤的转移和生长可能与下调COX-2表达,减少VEGF-C的产生和淋巴管生成有关。     

共接种淋巴管内皮细胞对乳腺癌细胞和骨肉瘤细胞在裸鼠体内生长和转移的影响

目的分析淋巴管生成对肿瘤生长和转移的影响。方法从人淋巴结中分离纯化淋巴管内皮细胞(HLyECs),将人乳腺癌细胞系和人骨肉瘤细胞系分别单独或与HLyECs共同接种于裸鼠皮下,比较肿瘤生长和肺转移的差别。用伊文氏蓝显示瘤周淋巴管;用人和小鼠PDPN的免疫组织化学显示肿瘤组织中的淋巴管。用MTT法分析淋巴管内皮细胞的增殖。结果与单纯接种组相比,共接种HLyECs促进乳腺癌细胞的生长和转移,瘤周和瘤内淋巴管密度增加(P<0.01),存在人和鼠PDPN阳性的淋巴管;而共接种HLyECs对骨肉瘤的生长和转移无影响,未见瘤内和瘤周淋巴管。与骨肉瘤细胞相比,乳腺癌细胞的条件培养基明显促进淋巴管内皮细胞增殖(P<0.01)。结论共接种淋巴管内皮细胞可以促进乳腺癌细胞的生长及癌组织中淋巴管生成。     

Smad4和VEGF-C的表达与乳腺癌淋巴管生成之间的关系

目的观察Smad4和血管内皮生长因子(VEGF)-C在人乳腺癌组织内的表达情况,分析Smad4和VEGF-C的表达与乳腺癌淋巴管生成及淋巴结转移之间的关系。方法取乳腺癌病例56例,其中,淋巴结转移组35例,无淋巴结转移组21例。应用免疫组化法和Western blot技术观察Smad4和VEGF-C在乳腺癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,检测乳腺癌组织内淋巴管生成情况。结果 Smad4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。而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=-0.314)。Western blot检测结果表明,VEGF-C蛋白在有淋巴结转移乳腺癌组织中的表达量高于其在无淋巴结转移乳腺癌组织内的表达量,而Smad4在有淋巴结转移乳腺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 VEGF-C在乳腺癌淋巴管的发生及淋巴结转移中发挥重要作用,与Smad4的表达呈负相关,Smad4可能通过调节VEGF-C蛋白的表达而抑制乳腺癌淋巴管生成和淋巴道转移的作用。     

表没食子儿茶素-3-没食子酸酯抑制乳腺癌裸鼠移植瘤淋巴管生成

目的 探讨表没食子儿茶素-3-没食子酸酯(EGCG)对人乳腺癌裸鼠皮下移植瘤淋巴管生成的影响及其作用机制.方法 建立裸鼠皮下移植瘤模型30例,随机分成5组,即生理盐水组、5-氟脲嘧啶(5-FU)组、20mg/kg EGCG组、10mg/kg EGCG组、5mg/kg EGCG组,观察瘤组织血管内皮生长因子C(VEGF-C)的表达情况,淋巴管内皮细胞透明质酸受体1(LYVE-1)标记淋巴管,检测淋巴管密度及面积;Western blotting检测移植瘤组织VEGF-C蛋白的表达情况.结果 免疫组织化学染色VEGF-C在20mg/kg EGCG处理组中的表达量明显低于生理盐水组和5-FU组,且VEGF-C的表达与EGCG成剂量依赖性;移植瘤周边淋巴管密度、面积在20mg/kg EGCG处理组中显著低于5-FU组和生理盐水组,差异有统计学意义;Western blotting结果显示,EGCG高剂量处理组VEGF-C蛋白明显低于生理盐水组.结论 EGCG可以抑制乳腺癌裸鼠移植瘤中VEGF-C的表达及淋巴管的生成.     

大肠癌组织VEGF-C、COX-2、Flt-4及nm23表达与淋巴管生成及淋巴结转移的关系

目的:探讨结直肠癌组织中血管内皮生长因子-C(VEGF-C)、环氧化酶-2(COX-2)、酪氨酸激酶受体(Flt-4)及其转移抑制基因nm23的表达与淋巴管生成、淋巴结转移的关系。方法:选取2005-09/2009-09南昌大学第二附属医院病理科大肠癌手术切除标本94例,采用酶组织化学方法及SP免疫组化法对大肠癌组织中VEGF-C、COX-2、Flt-4和nm23的表达及淋巴管的生成进行观察,分析大肠癌组织中VEGF-C、COX-2、Flt-4及nm23的表达与淋巴管生成及淋巴结转移之间的关系。结果:VEGF-C、COX-2、Flt-4及nm23在大肠癌和癌旁正常肠黏膜组织中的表达比较均具有统计学差异(P0.05)。VEGF-C及Flt-4的表达与Dukes分期、淋巴管计数和淋巴结的转移有显著相关性(P0.05);COX-2的表达与肿瘤大小、分化程度、浸润深度、肿瘤的分期、淋巴管计数和淋巴结的转移有显著相关性(P0.05);nm23的表达与分化程度、Dukes分期和淋巴结的转移有显著相关性(P0.05)。结论:VEGF-C、COX-2及Flt-4的表达与大肠癌淋巴管生成和淋巴结转移密切相关;nm23基因在大肠癌的浸润和淋巴结转移过程中起负性调控作用。     

乳腺癌组织中LVD、VEGF-C和MMP-9表达及其相关性

目的 检测乳腺浸润性导管癌(invasive ductal carcinoma,IDC)组织中的淋巴管密度(lymphatic vessel density,LVD)、VEGF-C及MMP-9的表达,探讨其临床意义.方法 收集80例乳腺IDC和20例乳腺增生性病变,应用免疫组化PV-6000两步法检测淋巴管内皮透明质酸受体1(LYVE-1)、VEGF-C和MMP-9的表达.结果 乳腺癌组织中LYVE-1标记的LVD、VEGF-C和MMP-9的表达明显高于乳腺增生性病变,差异均有统计学意义(P<0.01).LVD、VEGF-C与临床病理参数之间均无差异(P>0.05).MMP-9的表达水平在肿瘤直径>2 cm组和淋巴结转移阳性组明显升高(P<0.05和P<0.01);而在组织学分级之间表达的差异无统计学意义(P>0.05).LVD与VEGF-C的表达呈正相关关系(r=0.398,P<0.01);LVD和MMP-9之间无相关关系(P>0.05).结论 IDC中淋巴管生成增多,VEGF-C是乳腺癌中淋巴管生成的重要刺激因子,促进乳腺癌中淋巴管的生成;但乳腺癌淋巴管密度与淋巴道转移无关.MMP-9参与肿瘤的侵袭和转移的过程,促进乳腺癌淋巴道转移.     

血管内皮生长因子-C促进淋巴管内皮细胞的增殖、迁移和F-肌动蛋白重组

目的 研究血管内皮生长因子-C(VEGF-C)对于淋巴管内皮细胞增殖和迁移的作用，探讨VEGF-C促进淋巴管新生的机制。方法 从狗的胸导管分离和培养淋巴管内皮细胞。标记内皮细胞的VEGFR-3和F-肌动蛋白，在荧光显微镜和共聚焦激光扫描显微镜下观察。用VEGF-C刺激后，计数增殖细胞和迁移细胞，测量细胞迁移距离，并与bFGF和VEGF的作用进行比较。结果 淋巴管内皮细胞表达VEGFR-3，静脉内皮细胞为阴性。bFGF和VEGF-C促进淋巴管内皮细胞的增殖，VEGF-C的作用比bFGF强。与对照组相比，bFGF、VEGF和VEGF-C组引起迁移细胞的数目增多和迁移距离增大，VEGF-C的作用最强。在VEGF-C组的迁移细胞，F-肌动蛋白和应力纤维明显增多。结论 淋巴管内皮细胞特异性表达VEGFR-3，VEGF-C促进淋巴管内皮细胞的增殖和迁移，引起F-肌动蛋白的重组和应力纤维形成。     

喉癌中血管内皮生长因子C与淋巴转移的关系

目的：探讨喉癌中血管内皮生长因子C（Vascular endothelial growth factor-C，VEGF-C）的表达与淋巴道转移的关系。方法：免疫组化SP法，对54例喉癌组织行VEGF-C检测及癌周组织毛细淋巴管计数，应用全自动图像分析仪对染色结果进行定量测定，以平均灰度值表示VEGF-C的染色强度。结果：喉癌组织内VEGF-C表达高于声带息肉（P〈0．05）；颈淋巴结转移组高于非转移组（P〈0．01）。癌周组织毛细淋巴管密度高于对照组正常喉组织（P〈0．01）；颈淋巴结转移组高于非转移组（P〈0．01）。喉癌组织内VEGF-C表达与癌周组织淋巴管密度呈正相关（r=0．603，P〈0．01）。结论：喉癌组织中VEGF-C的表达与癌周毛细淋巴管密度关系密切，VEGF-C高表达促进淋巴管增殖，促进淋巴道转移。     

D-Limonene对小鼠移植瘤生长及淋巴管生成的影响

目的:观察右旋柠烯对小鼠移植瘤生长及淋巴管生成的影响,并探讨其作用机制。方法:皮下注射肉瘤(S180)腹水型瘤株构建小鼠移植瘤模型,给予D-Lim onene干预,免疫组化染色观察瘤细胞V EG F-C表达,LY V E-1标记淋巴管,观察其分布。结果:对照组瘤细胞V EG F-C表达较强,瘤周边部淋巴管较多,有淋巴结、肺转移。用药组瘤细胞V EG F-C表达较弱;瘤周边部淋巴管较少,未见淋巴结、肺转移。结论:D-Lim onene有抑制移植瘤内瘤细胞V EG F-C表达和淋巴管生成的作用,有可能降低肿瘤的淋巴道转移。     

Expression of vascular endothelial growth factor-C and its receptor in invasive micropapillary carcinoma of the breast

Invasion to lymphatic vessels and metastasis to lymph nodes are frequent complications in invasive micropapillary carcinoma (IMPC) of human breast cancer. Vascular endothelial growth factor-C (VEGF-C) and its receptor, VEGFR-3 have been implicated as the important factors in the formation of lymphatic vessels and recent experimental evidence strongly suggests that lymphangiogenesis in tumor promotes lymphatic metastasis. To clarify the mechanism of its occurrence, the expression of VEGF-C, VEGFR-3 and lymphatic vessel density (LVD) was examined in 40 cases of IMPC (pure and mixed type) and in 40 cases of pseudo-IMPC. Cytoplasmic expression of VEGF-C and VEGFR-3 were more frequent in tumor cells of IMPC compared to those of pseudo-IMPC. A significant positive correlation was found between the expression of VEGF-C and VEGFR-3 in both IMPC and pseudo-IMPC. The expression of VEGF-C was also significantly associated with higher peritumoral LVD, lymphatic invasion and number of lymph node metastasis in IMPC. These findings suggest that VEGF-C promotes the proliferation of peritumoral lymphatic vessels and that lymphatic invasion and metastasis to lymph nodes are frequently induced in IMPC of breast.     

Inhibition of VEGFR-3 activation in tumor-draining lymph nodes suppresses the outgrowth of lymph node metastases in the MT-450 syngeneic rat breast cancer model

For many types of human cancer, the expression of vascular endothelial growth factor-C (VEGF-C) correlates with enhanced tumor-associated lymphatic vessel density, metastasis formation and poor prognosis. In experimental animals, VEGF-C produced by primary tumors can induce lymphangiogenesis within and/or at the periphery of the tumor, and promotes metastasis formation. Tumor-induced lymphangiogenesis is therefore thought to expedite entry of tumor cells into the lymphatic vasculature and their trafficking to regional lymph nodes, thereby fostering metastatic dissemination. Tumour-produced VEGF-C can also drain to the regional lymph nodes and induce lymphangiogenesis there. Whether this activity promotes metastasis formation remains unclear. To address this issue we manipulated VEGF-C activity and VEGFR-3 activation in the lymph nodes draining syngeneic rat breast cancers using intra-dermal delivery of either recombinant VEGF-C or VEGFR-3 blocking antibodies to induce or suppress lymph node lymphangiogenesis, respectively. Recombinant VEGF-C induced lymph node lymphangiogenesis, but was not sufficient to promote metastasis formation by poorly metastatic NM-081 breast tumours. Conversely, inhibition of lymph node lymphangiogeneis induced by highly metastatic MT-450 breast tumours suppressed the outgrowth of lymph node metastases, but not the initial colonization of the lymph nodes. Lung metastasis was also not affected. We conclude that tumor-derived VEGF-C draining to regional lymph nodes promotes the outgrowth of lymph node metastases. VEGF-C may induce lung metastasis independently of its effects on lymph node metastasis.     

人胃癌组织中VEGF-C及其受体Flt-4的表达

目的：观察VEGF-C和Fit-4在胃癌组织及淋巴管的表达，探讨癌细胞淋巴管转移机理。方法：用免疫组化方法检测人胃癌早期和进展期癌细胞和淋巴管VEGF-C和Fit-4的表达情况。结果：在各期胃癌的癌细胞中均见到VEGF-C和Fit-4阳性表达，淋巴管内皮细胞仅见到Fit-4阳性表达；进展期胃癌两种蛋白的表达率和表达强度都高于早期癌。结论：癌细胞VEGF-C和Fit-4的表达与肿瘤进展呈正相关；淋巴管上Fit-4的表达也与胃癌的进展呈正相关。推测VEGF-C可能通过其受体Fit-4诱导胃癌组织淋巴管发生。     

The extent of retraction clefts correlates with lymphatic vessel density and VEGF-C expression and predicts nodal metastasis and poor prognosis in early-stage breast carcinoma

Although the earliest feature of disseminated disease in breast cancer is regional lymph node involvement, little is known about the mechanisms whereby cancer cells interact with lymphatic endothelial cells and enter the lymphatic system. We have previously reported that the extensive presence of retraction clefts in breast carcinomas highly significantly correlates with lymphatic tumor spread and predicts poor outcome, suggesting that retraction clefts are not just fixation artifacts, but real potential spaces that are exaggerated by tissue processing and may reflect an early stage of lymphatic invasion. In this study, we examined the correlation between the extent of retraction clefts and lymphangiogenesis, as assessed by lymphatic vessel density and vascular endothelial growth factor-C (VEGF-C) expression in a series of 256 early-stage breast carcinomas. The presence and extent of retraction clefts around tumor cell nests was determined by review of all hematoxylin- and eosin-stained tumor sections. Lymphatic vessels were detected by podoplanin immunohistochemistry and lymphatic vessel density was measured using the hot-spot method. The expression of VEGF-C in the tumor cells was determined by immunohistochemistry and analyzed semiquantitatively on a four-tiered scale. High levels of retraction clefts, peritumor lymphatic vessel density and VEGF-C expression at the invasive edge in breast carcinomas significantly correlated with tumor size, histological grade, lymphatic invasion and nodal metastasis. Breast carcinomas showing extensive retraction clefts (>20% of tumor volume) were found to have significantly higher lymphatic vessel density and VEGF-C expression levels compared to tumors without this feature. High retraction clefts, peritumor lymphatic vessel density and VEGF-C expression predicted poor outcome in breast carcinomas. Our results support the hypothesis that retraction clefts are real potential spaces that may represent 'pre-lymphatic spaces' facilitating initial lymphatic invasion and that growth factors secreted by the tumor cells may stimulate tumor-associated lymphangiogenesis by promoting the endothelialization of these 'pre-lymphatic channels'.     

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。     

Targeting COX-2 and EP4 to control tumor growth, angiogenesis, lymphangiogenesis and metastasis to the lungs and lymph nodes in a breast cancer model

We reported that cyclo-oxygenase (COX)-2 expression in human breast cancer stimulated cancer cell migration and invasiveness, production of vascular endothelial growth factor (VEGF)-C and lymphangiogenesis in situ, largely from endogenous PGE2-mediated stimulation of prostaglandin E (EP)1 and EP4 receptors, presenting them as candidate therapeutic targets against lymphatic metastasis. As human breast cancer xenografts in immuno-compromised mice have limitations for preclinical testing, we developed a syngeneic murine breast cancer model of spontaneous lymphatic metastasis mimicking human and applied it for mechanistic and therapeutic studies. We tested the roles of COX-2 and EP receptors in VEGF-C and -D production by a highly metastatic COX-2 expressing murine breast cancer cell line C3L5. These cells expressed all EP receptors and produced VEGF-C and -D, both inhibited with COX-2 inhibitors or EP4 (but not EP1, EP2 or EP3) antagonists. C3H/HeJ mice, when implanted SC in both inguinal regions with C3L5 cells suspended in growth factor-reduced Matrigel, exhibited rapid tumor growth, tumor-associated angiogenesis and lymphangiogenesis (respectively measured with CD31 and LYVE-1 immunostaining), metastasis to the inguinal and axillary lymph nodes and the lungs. Chronic oral administration of COX-1/COX-2 inhibitor indomethacin, COX-2 inhibitor celecoxib and an EP4 antagonist ONO-AE3-208, but not an EP1 antagonist ONO-8713 at nontoxic doses markedly reduced tumor growth, lymphangiogenesis, angiogenesis, and metastasis to lymph nodes and lungs. Residual tumors in responding mice revealed reduced VEGF-C and -D proteins, AkT phosphorylation and increased apoptotic/proliferative cell ratios consistent with blockade of EP4 signaling. We suggest that EP4 antagonists deserve clinical testing for chemo-intervention of lymphatic metastasis in human breast cancer.     

Mammary cancer gene therapy targeting lymphangiogenesis: VEGF-C siRNA and soluble VEGF receptor-2, a splicing variant

Metastasis contributes significantly to cancer mortality, and the most common pathway of initial dissemination is via the afferent ducts of the lymphatics. Overexpression of vascular endothelial growth factor (VEGF)-C has been associated with lymphangiogenesis and lymph node metastasis in a multitude of human neoplasms, including breast cancers. We recently reported that both VEGF-C siRNA and endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2, a new splicing variant) inhibit VEGF-C function and metastasis in a mouse model of metastatic mammary cancer. Here we briefly review our previous experimental work, specifically targeting tumor lymphangiogenesis, in which metastatic mouse mammary cancers received direct intratumoral injections of either expression vectors VEGF-C siRNA or esVEGFR-2, or the empty plasmid vector, once a week for 6 or 8 weeks, followed by in vivo gene electrotransfer of the injected tumors. Throughout our study, both tumor lymphangiogenesis and the multiplicity of lymph node metastasis were significantly inhibited, with an overall reduction in tumor growth, by both VEGF-C siRNA and esVEGFR-2; further, a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells was observed with both treatments. Thus, therapeutic strategies targeting lymphangiogenesis may have great clinical significance for the treatment of metastatic human breast cancer.     

VEGF-C在卵巢癌局部淋巴结内淋巴管生成中的作用

目的观察血管内皮生长因子-C(VEGF-C)在卵巢癌组织内的表达,分析其与卵巢癌局部淋巴结内淋巴管生成之间的关系。方法取卵巢癌64例,其中,有淋巴结转移40例,无淋巴结转移24例。应用免疫组化法和Western blot技术观察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,检测卵巢癌局部淋巴结内淋巴管生成情况。结果 VEGF-C主要表达于卵巢癌细胞浆和胞膜以及癌组织周围浸润的炎性细胞,在有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。Western blot检测结果表明,VEGF-C蛋白在有淋巴结转移的卵巢癌组织中的表达量高于其在无淋巴结转移的卵巢癌组织内的表达量。D2-40表达于卵巢癌局部淋巴结内的淋巴管内皮细胞,在有转移的淋巴结内可见大量新生的淋巴管,淋巴管腔内存在入侵的肿瘤细胞,在无转移的淋巴结内观察到新生的淋巴管。在无淋巴结转移组病例中,卵巢癌组织VEGF-C阳性者局部淋巴结内淋巴管密度明显高于VEGF-C阴性者淋巴结内的淋巴管密度。结论 VEGF-C的表达与卵巢癌淋巴结转移密切相关,卵巢癌在发生局部淋巴结转移之前存在淋巴结内淋巴管生成的现象,卵巢癌组织内VEGF-C的表达在卵巢癌局部淋巴结内的淋巴管生成中可能发挥重要作用。     

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。