胃癌中D2-40和CD34的表达及临床意义

目的 探讨D2-40和CD34在胃癌组织中的表达及D2-40阳性的淋巴管密度（LVD）和CD34阳性的微血管密度（MVD）与临床病理特征和预后的关系。方法 采用组织芯片和免疫组化技术检测108例胃癌和36例癌旁组织中D2-40和CD34的表达情况,并分别计数D2-40阳性的LVD和CD34阳性的MVD,分析两者与临床病理特征和预后的关系。结果 D2-40在胃癌和癌旁组织中的阳性表达率分别为85.2％（92／108）和22.2％（8／36）,差异有统计学意义（P=0.000）;CD34在胃癌组织中的阳性表达率为94.4％（102／108）,高于癌旁组织的36.1％（13／36）,差异有统计学意义（P=0.000）。胃癌组织中LVD和MVD计数分别为10.14±5.37和45.32±15.78,显著高于癌旁组织中的3.38±1.69和4.92±1.26,差异均有统计学意义（P均为0.000）;单因素分析显示两者与肿瘤大小、浸润深度、淋巴结转移、TNM分期有关,与性别、年龄无关。Cox多因素分析显示肿瘤大小、浸润深度、淋巴结转移、TNM分期及MVD和LVD是胃癌预后的独立影响因素。Kaplan-Meier生存分析显示,乏淋巴管组的中位生存时间为69.0个月（95％ CI：59.91～77.20个月）,高于富淋巴管组的33.0个月（95％ CI：23.20～42.66个月）;乏微血管组的中位生存时间为67.0个月（95％ CI：58.10～76.39个月）,高于富微血管组34.0个月（95％ CI：24.63～44.02个月）,上述差异均有统计学意义（P＜0.05）。结论 D2-40标记的LVD和CD34标记的MVD与胃癌的临床病理特征密切相关,有望成为胃癌发展及预后的预测指标。     

胃癌淋巴管密度、微血管密度水平及其临床意义

目的 探讨胃癌组织中淋巴管密度（LVD）和微血管密度（MVD）水平及两者与胃癌临床病理特征的关系。方法 收集本院2004年2月至2007年2月手术切除的68例胃癌患者肿瘤组织,分别采用D2-40和CD31标记胃癌组织中淋巴管和血管,采用免疫组化法检测瘤周及瘤内D2 40、CD31表达情况并计算LVD和MVD,分析瘤周及瘤内LVD、MVD水平与临床病理参数（肿瘤大小、淋巴结转移、脏器转移、TNM分期、性别、年龄、分化程度、Lauren分型及病理类型）和预后的关系。结果 68例患者瘤内和瘤周LVD分别为（4.6±2.0）个和（8.2±3.5）个,瘤内和瘤周MVD分别为（46.3±16.5）个和（47.6±15.3）个;瘤周LVD与肿瘤大小、淋巴结转移、脏器转移及TNM分期有关（P＜0.05）,与性别、年龄、分化程度、Lauren分型及病理类型均无关（P＞0.05）;瘤内LVD、瘤内及瘤周MVD与以上参数均无关（P＞0.05）;全组中位总生存期（OS）为48.6个月,其中瘤周低LVD者的中位OS为31.0个月,低于瘤周高LVD的43.0个月（P＜0.05）;瘤周高MVD者的中位OS为46.0个月,而瘤周低MVD者为48.0个月,差异无统计学意义（P＞0.05）。结论 瘤周LVD与胃癌的临床病理特征及预后密切相关,可能成为胃癌发展及预后的预测指标。     

胃癌组织中血管内皮生长因子的表达对血管和淋巴管生成的影响及其预后意义

目的 研究胃痛组织中血管内皮生成因子(VEGF)-A、VEGF-C和VEGF-D的表达对血管和淋巴管生成的影响及其预后意义.方法 采用免疫组化法检测123例原发性胃癌组织中VEGF-A、VEGF-C和VEGF-D的表达,采用D2-40和CD34免疫组化双染法分别标记淋巴管和血管,并测定淋巴管密度(LVD)和血管密度(MVD).采用单因素分析VEGF-A、VEGF-C和VEGF-D表达与胃癌临床病理特征的关系;采用Kaplan-Meier法和Log rank检验评价VEGF-A、VEGF-C和VEGF-D表达与胃癌患者预后的关系,并用Cox比例风险模型进行多因素分析.结果 123例胃癌组织中,VEGF-A、VEGF-C和VEGF-D的高表达率分别为64.2%、65.9%和41.5%.VEGF-A、VEGF-C或VEGF-D高表达及两两高表达均与LVD有关(均P＜0.05);VEGF-A和VEGF-C高表达还与浸润深度、淋巴管浸润、静脉浸润、淋巴结转移和MVD有关(均P＜0.05);VEGF-C和VEGF-D高表达均与淋巴管浸润和淋巴结转移有关(均P＜0.05).VEGF-A、VEGF-C或VEGF-D高表达者的生存时间均明显短于其低表达者(均P＜0.05),其中VEGF-A和VEGF-C均高表达者的生存时间最短(56个月).VEGF-A的表达水平、MVD、淋巴结转移及浸润深度是影响胃癌患者预后的独立因素.结论 VEGF-A和VEGFC均高表达的胃癌有更强的促进血管和淋巴管生成的能力,并可促进肿瘤转移和影响患者预后;VEGF-C和VEGF-D可共同介导淋巴管生成,促进淋巴结转移;但仅VEGF-A高表达是影响患者预后的独立危险因素.     

Chalkley Microvessel but not Lymphatic Vessel DensityCorrelates with Axillary Lymph Node Metastasis in PrimaryBreast Cancers

This study aimed to investigate tumor microvessel density (MVD) and lymphatic vessel density (LVD) usingthe Chalkley method as predictive markers for the risk of axillary lymph node metastasis and their relationshipto other clinicopathological parameters in primary breast cancer cases. Forty two node-positive and eightynode-negative breast cancers were immunostained for CD34 and D2-40. MVD and LVD were counted by theChalkley method at x400 magnification. There was a positive significant correlation of the MVD with the tumorsize, coexisting ductal carcinoma in situ (DCIS) and lymph node metastases (P<0.05). In multivariate analysis,the MVD (2.86-4: OR 5.87 95%CI 1.05-32; >4: OR 20.03 95%CI 3.47-115.55), lymphovascular invasion (OR3.46, 95% CI 1.13-10.58), and associated DCIS (OR 3.1, 95%CI 1.04-9.23) independently predicted axillarylymph node metastasis. There was no significant relationship between LVD and axillary lymph node metastasis.However, D2-40 was a good lymphatic vessel marker to enhance the detection of lymphatic invasion compared toH and E staining. In conclusion, MVD by the Chalkley method, lymphovascular invasion and associated DCIScan be additional predictive factors for axillary lymph node metastases in breast cancer. No relationship wasidentified between LVD and clinicopathological variables, including axillary lymph node metastasis.     

直肠良恶性肿瘤中肿瘤相关巨噬细胞和微血管及淋巴管生成的关系

目的：探讨直肠良恶性肿瘤组织中微血管密度（MVD）及淋巴管密度（LVD）与肿瘤相关巨噬细胞（TAMs）数量的相关性。方法：采用免疫组化的方法,用CD68标记TAMs,分别用CD31和D2-40标记微血管和淋巴管,光镜下对TAMs,MVD及LVD进行计数,分析。结果：直肠腺癌组织中的TAMs,MVD及LVD计数明显高于直肠腺瘤型息肉组织（P〈0.01）;在直肠腺癌组中,TAMs与MVD和LVD有明显相关性（TAMs与MVD：P〈0.01;TAMs与LVD：P〈0.01）,且MVD与直肠癌淋巴结转移（P〈0.01）和分化程度（P〈0.05）密切相关;而TAMs和LVD仅与淋巴结转移有显著相关性（P〈0.01,P〈0.05）。结论：TAMs,MVD及LVD可能是反映直肠腺癌发生、发展、转移及侵袭能力的生物学指标,TAMs在肿瘤中的浸润可能与肿瘤血管及淋巴管的生成有关。     

直肠良恶性肿瘤中肿瘤相关巨噬细胞和微血管及淋巴管生成的关系

目的:探讨直肠良恶性肿瘤组织中微血管密度(MVD)及淋巴管密度(LVD)与肿瘤相关巨噬细胞(TAMs)数量的相关性。方法:采用免疫组化的方法,用CD68标记TAMs,分别用CD31和D2-40标记微血管和淋巴管,光镜下对TAMs,MVD及LVD进行计数,分析。结果:直肠腺癌组织中的TAMs,MVD及LVD计数明显高于直肠腺瘤型息肉组织(P<0.01);在直肠腺癌组中,TAMs与MVD和LVD有明显相关性(TAMs与MVD:P<0.01;TAMs与LVD:P<0.01),且MVD与直肠癌淋巴结转移(P<0.01)和分化程度(P<0.05)密切相关;而TAMs和LVD仅与淋巴结转移有显著相关性(P<0.01,P<0.05)。结论:TAMs,MVD及LVD可能是反映直肠腺癌发生、发展、转移及侵袭能力的生物学指标,TAMs在肿瘤中的浸润可能与肿瘤血管及淋巴管的生成有关。     

淋巴管密度在甲状腺乳头状癌和滤泡癌的表达及意义

[目的]探讨淋巴管密度（LVD）在甲状腺乳头状癌（PTC）和滤泡癌的表达及意义。[方法]采用免疫组化技术,以D2-40标记淋巴管内皮,CD31标记血管内皮,对105例PTC、18例甲状腺滤泡癌和21例滤泡性腺瘤进行LVD和微血管密度（MVD）的检测。对LVD与乳头状癌的临床病理资料的关系,及乳头状癌和滤泡癌中MVD和LVD的表达差异进行了统计分析。[结果]（1）PTC中均可见D2-40阳性淋巴管,其瘤周LVD较瘤内为高,淋巴结转移组（瘤内6.80±4.40;瘤周13.63±5.09）较无转移组（瘤内4.30±3.06;瘤周10.17±4.53）为高,两组比较有统计学差异（P〈0.01）。（2）甲状腺乳头状癌的瘤内LVD与TNM分期有关,高分期组（Ⅲ期/Ⅳ期）的瘤内LVD（7.33±4.79）较低分期组（Ⅰ期/Ⅱ期,5.16±3.71）为高,两者相比有统计学差异（P〈0.05）。（3）甲状腺乳头状癌的瘤内LVD（5.47±3.93）较滤泡癌的瘤内LVD（1.56±1.92）为高,两者相比,差异具有统计学意义（P〈0.05）。[结论]甲状腺乳头状癌LVD与淋巴结转移密切相关,瘤周淋巴管的扩张形态和相对较高的LVD在甲状腺乳头状癌淋巴道转移中可能发挥了重要的作用。     

早期胃癌淋巴管密度预测淋巴结转移的研究

目的:检测淋巴管内皮标志物D2-40计算早期胃癌淋巴管密度(LVD),探讨LVD与早期胃癌有无淋巴结转移之间的关系.方法:用免疫组化SP染色法,对80例早期胃癌淋巴结未发生转移与20例早期胃癌淋巴结发生转移的癌周检测D2-40标记阳性LVD的表达水平,并进行统计学分析.结果:D2-40标记阳性LVD在早期胃癌伴有淋巴结转移癌周高于早期胃癌不伴有淋巴结转移癌周(P＜0.05),光镜下LVD的截断(cut-off)值为18.50个.结论:早期胃癌伴有淋巴结转移癌周的LVD高于早期胃癌不伴有淋巴结转移癌周,D2-40阳性LVD可用来判断有无淋巴结转移.     

Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma

BACKGROUND: Lymphatic vessel density (LVD) and microvessel density (MVD) are important parameters for assessing the malignant potential of tumors and patient survival. In this report, the authors defined LVD as the density of D2-40-positive lymphatic vessels and MVD as the density of CD105-positive microvessels per unit area of tissue. It was reported previously that vascular endothelial growth factor C (VEGF-C) is a major modulator of LVD and MVD. The objectives of this study were to clarify the clinical and prognostic significance of both LVD and MVD in oral squamous cell carcinoma (OSCC) and to elucidate the lymphangiogenic and angiogenic activities of VEGF-C in cancer tissues. METHODS: In total, 110 OSCC tissue samples were evaluated for LVD, MVD, and expression of VEGF-C using immunohistochemistry. Correlations among these parameters and clinicopathologic factors were examined. RESULTS: LVD was significantly higher in tumors that had very high expression of VEGF-C compared with tumors that had no/weak expression of VEGF-C. LVD correlated well with lymph node metastasis (P < .001). MVD was correlated significantly with positive lymph node metastasis (P < .001) but not with VEGF-C expression. In contrast, high expression of VEGF-C was correlated significantly with advanced tumor status (P = .041). Survival rates were lower in patients who had higher LVD (P < .001), higher MVD (P = .0028), and strong VEGF-C expression (P = .048). CONCLUSIONS: Lymphangiogenesis predominantly influenced metastasis-free survival. The current results suggested that LVD is a more useful tool than MVD and VEGF-C for deciding on therapeutic strategies in patients with OSCC.     

Correlation between expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and angiogenesis in gastric cancer

Objective： To investigate the relationship between matrix metalloproteinase-2 （MMP-2）, MMP-9 as well as microvessel density （MVD） and their clinicopathological features in gastric cancer. Methods： The expression of MMP-2, MMP-9 and MVD were detected by immunohistochemistry SP method on 65 cases of gastric cancer tissue and 32 adjacent gastric mucosa. Results： The positive expression of MMP-2, MMP-9 and MVD in cancer group were significantly higher than those of adjacent mucosa group （P〈0.01）. The positive expression of MM P-2 and MMP-9 had closely correlation with clinical features of lymphatic metastasis, pathological type and stages （P〈0.05）, and the high level of CD 34 had correlation with metastasis and stages （P〈0.01）. The positive expression of MMP-2 and MMP-9 showed significant correlation with the level of MVD. Prognosis was mostly affected by lymphatic metastasis and stages of clinical features. The low cum survival rate was showed in the groups of positive expression of MMP-2, MMP-9 and high level of MVD. Conclusion： MMP-2, MMP-9 and MVD play an important role in metastases, invasion and prognosis of gastric cancer, which is a valuable maker to evaluate the prognosis.     

Clinicopathological significance of lymphatic vessel density marked by D2-40 and E-cadherin expression in non-small-cell lung cancer

The aim of our study is to investigate the relationship between lymphatic vessel density (LVD) marked by D2-40 and E-cadherin expression and the clinicopathological characteristics of patients with non-small-cell lung cancer (NSCLC). Immunohistochemical analysis was used to detect the expression of D2-40 and E-cadherin in 46 archival surgical specimens of human NSCLC and 10 cases of benign pulmonary disease. The LVD positively stained with D2-40 was observed and counted. The LVD was mainly distributed in the tumor borderline. The LVD in NSCLC tissues was significantly higher than in benign lesions (p?<?0.001), and the LVD marked by D2-40 was significantly associated with lymph node metastasis (p?<?0.001). The reduced expression of E-cadherin was present in NSCLC tissues. The positive rate of E-cadherin expression was negatively correlated with TNM stage (p?=?0.027), pathological grade (p?=?0.032), and lymph node metastasis (p?=?0.014), and not significantly correlated with histologic classification (p?=?0.714) in NSCLC tissues. A correlation analysis showed that high LVD marked by D2-40 was correlated with reduced E-cadherin expression in NSCLC tissues (t?=?36.476, p?<?0.001). The new monoclonal antibody D2-40 can specifically recognize lymphatic endothelial cells in NSCLC tissue. The relationship between LVD marked by D2-40 and the reduced expression of E-cadherin and lymph node metastasis in NSCLC was demonstrated. The detection of D2-40 and E-cadherin may be used as an indicator of lymph node metastasis in NSCLC.     

MMP-9、uPA及CD34与胃癌侵袭和转移及其相关性

目的：对基质金属蛋白酶-9（Metrix metalloproteinase-9,MMP-9）、尿激酶型纤溶酶原激活物（uro-kinase-type plasminogen activator,uPA）及血管标志物CD34与胃癌侵袭和转移的关系及其相关性进行研究。方法：选择临床病理资料完整的胃癌蜡块标本54例,正常胃黏膜标本15例作对照。采用SP免疫组化方法检测MMP-9、uPA、CD34的表达。结果：MMP-9、uPA在胃癌组织中高表达,并随分级的降低、淋巴转移的发生、临床分期的提高而明显增高（P均〈0.05）。CD34在胃癌组织中高表达,并随分级的降低、远隔转移的发生、临床分期的提高而明显增高（P均〈0.05）。胃癌中MMP-9与CD34的表达呈正相关（P〈0.01）;uPA与CD34的表达呈正相关（P〈0.01）。结论：MMP-9、uPA、CD34对胃癌的发生、发展、侵袭和转移起重要的促进作用。MMP-9、uPA、CD34在胃癌的发生、发展、侵袭和转移中相互促进,相互协调,关系密切。MMP-9、CD34、uPA各自都可以成为胃癌诊断和预后估计的指标。CD34可以作为胃癌中微血管密度（microvesseldensity,MVD）的有效标记物,同时为胃癌的分子生物学治疗提供新靶点。     

Lymphatic vessel density as prognostic factor in breast carcinoma: relation to clinicopathologic parameters

Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic microvessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immunostained for D2-40, CD31 and VEGF. Median lymphatic and blood microvessel densities, as well as VEGF expression, were related to each other and to clinicopathologic parameters including lymph node (LN) status. The efficacy of haematoxylin and eosin (H&E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H&E. VEGF was expressed in 85%of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H&E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis.     

Angiogenesis and Lymphangiogenesis in Salivary Gland Adenoid Cystic Carcinoma and Mucoepidermoid Carcinoma

Background and Purpose: This study aimed to investigate the immunohistochemical expression of CD31 and podoplanin in order to examine angiogenesis and lymphangiogenesis, respectively in common malignant tumors of salivary glands. Materials and Methods: Forty formalin-fixed, paraffinated blocks (20 adenoid cystic carcinoma and 20 mucoepidermoid carcinoma blocks) were selected from the medical archives of Amir A’lam Hospital of Tehran, Iran. Sections from the blocks were stained by CD31 and D2-40 markers via immunohistochemistry. Clinical and demographic information was extracted from the patients’ records. Findings: There was a significant difference between tumors in terms of intratumoral microvessel density (MVD) (P< 0.001), total MVD (P< 0.001), and intratumoral lymphatic vessel density (LVD) (P= 0.011). In mucoepidermoid carcinoma, intratumoral MVD and LVD were greater than peritumoral MVD and LVD (P= 0.001 and P< 0.001, respectively). In mucoepidermoid carcinoma, there was no relationship between histological grade with MVD (total, intratumoral or peritumoral) or LVD (total, intratumoral or peritumoral) (P> 0.05). A similar finding was reported with respect to the histopathological grade of adenoid cystic carcinoma (P> 0.05). Conclusion: The higher level of angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma, specifically at the center of tumor, compared to adenoid cystic carcinoma, may be attributed to differences in the clinical behaviors and metastasis of tumors. Moreover, considering the high LVD at the center of tumor in mucoepidermoid carcinoma and infrequency of metastasis to regional lymph nodes in adenoid cystic carcinoma, it can play a significant role in metastasis to regional lymph nodes.     

Prognostic value of blood and lymphatic vessel markers in tongue cancer: A systematic review

Tongue squamous cell carcinoma (TSCC) has a poor prognosis due to its early metastasis through blood and lymphatic vessels. We undertook a systematic review to investigate the prognostic significance of blood microvessel density (MVD) and lymphatic vessel density (LVD) in TSCC patients. We carried out a systematic search in Ovid Medline, Scopus, and Cochrane libraries. All studies that evaluated the prognostic significance of MVD/LVD markers in TSCC were systematically retrieved. Our results showed that MVD/LVD markers, CD31, CD34, CD105, factor VIII, lymphatic vessel endothelial hyaluronan receptor‐1, and D2‐40 were evaluated in TSCC patients until 28 June 2018. Six out of 13 studies reported markers that were associated with poor prognosis in TSCC. Two out of three studies suggested that a high number of D2‐40⁺ vessels predicated low overall survival (OS); the third study reported that the ratio of D2‐40⁺ over factor VIII⁺ vessels is associated with low OS. Most of the other markers had controversial results for prognostication. We found higher expression of MVD/LVD markers were commonly, but not always, associated with shorter survival in TSCC patients. It is therefore not currently possible to recommend implementation of these markers as reliable prognosticators in clinical practice. More studies (especially for D2‐40) with larger patient cohorts are needed.     

bFGFR、COX-2和MVD在胃癌中的表达及其与浸润转移的关系

目的 探讨碱性成纤维生长因子受体（bFGFR）、环氧合酶-2（COX-2）和微血管密度（MVD）与胃癌浸润、转移的关系。方法 选择80例手术切除的胃癌标本为观察组,40例慢性浅表性胃炎为对照组,应用免疫组织化学方法检测组织中bFGFR、COX-2和MVD的表达情况。结果 bFGFR及COX-2在胃癌患者中的阳性率为50.0%和52.5%。在对照组的阳性率分别为5.0%和0,差异均有统计学意义(P<0.01)。MVD在胃癌及对照组中的表达分别为（46.9±2.2）和（26.2±2.3）,差异有统计学意义（P<0.01）。三者的表达与肿瘤的浸润、淋巴及远处转移呈正相关(P<0.01或P<0.05),与肿瘤大小、分化程度无关(P>0.05)。bFGFR阳性和COX 2阳性组MVD值（48.7±10.2、49.6±11.6）均高于bFGFR阴性和COX-2阴性组（33.6±5.2、32.7±4.5,P<0.01）。bFGFR与COX-2的表达呈正相关（γ=0.700,P=0.0000）,二者在胃癌组织中的阳性表达强度与淋巴、远处转移呈正相关（P<0.01）。）结论 胃癌组织中bFGFR、COX-2和MVD的表达与胃癌的浸润、转移密切相关,三者在肿瘤血管形成中可能存在相互协同作用。三者的阳性表达可作为胃癌生长,转移的重要判定指标。     

环氧化酶-2及其抑制剂与结直肠癌微血管和淋巴管生成的研究

目的 探讨环氧化酶-2(COX-2)在结直肠癌组织的表达与肿瘤生物学特征、微血管生成及淋巴管生成的关系及其抑制剂塞来昔布的抗肿瘤作用和机制.方法 应用免疫组化方法 检测64例结直肠癌组织中COX-2的表达、微血管形成及淋巴管生成,分析其相关性及与临床病理参数联系.临床晚期直肠癌患者7例,给予塞来昔布灌肠治疗15天,对活检肿瘤组织微血管及淋巴管进行对比.结果 COX-2的表达与结直肠癌的分期(P=0.003)和组织学类型(P=0.004)相关;COX-2高表达组微血管密度(MVD)和淋巴管密度(LVD)均高于COX-2低表达组(P<0.05).塞来昔布灌肠治疗后直肠癌微血管密度下降,淋巴管密度无差异.结论 COX-2可能通过促进淋巴管及微血管生成参与了结直肠癌的发生与发展.COX-2抑制剂塞来昔布可抑制直肠癌微血管生成.     

宫颈癌中iNOS的表达与肿瘤新生淋巴管及VEGF-C的关系

目的:探测人宫颈癌中的诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、血管内皮生长因子-C(vascular endothelial growth factor,VEGF-C)的表达与D2-40标记的淋巴管密度的关系.方法:采用免疫组化SP法检测宫颈鳞状细胞癌中iNOS、VEGF-C的表达情况,并用D2-40进行癌组织淋巴管染色,测定其淋巴管密度(lymphatic vessel density,LVD),另取正常宫颈组织10例作对照,观察上述因子在宫颈癌及正常宫颈中的表达及其与肿瘤病理参数之间的相关性.结果:与正常宫颈组织相比,宫颈癌组织中具有更高的iNOS、VEGF-C的表达率及淋巴管密度(t=2.39、3.08,P=0.021、0.003).与无淋巴结转移组相比,淋巴结转移组具有更高的iNOS、VEGF-C阳性表达率(P =0.044、0.035)及淋巴管密度(t=3.79,P＜0.001);iNOS、VEGF-C阳性共表达与肿瘤淋巴结转移之间存在正相关(P=0.046),宫颈癌组织中iNOS、VEGF-C的表达具有相关性(P＜0.001).结论:iNOS、VEGF-C在宫颈癌组织中呈过表达,其与宫颈癌的淋巴转移关系密切;iNOS可能通过催化产生NO上调VEGF-C的表达,诱导肿瘤淋巴管生成,导致宫颈癌的淋巴道转移.iNOS、VEGF-C均参与宫颈的发展、浸润和转移,可作为评估宫颈癌的生物学行为和判断预后的指标.针对iNOS、VEGF-C的靶向治疗可成为宫颈癌治疗的新靶点.     

乳腺癌淋巴管密度的临床意义

目的探讨乳腺癌组织中淋巴管密度（LVD）与临床病理参数的关系。方法采用免疫组化方法对100例乳腺癌组织和20例乳腺纤维腺瘤组织中LYVE-1的表达进行检测,计数LVD,分析LVD与乳腺癌淋巴结转移及其它病理参数之间的相互关系。结果乳腺癌组织中LVD显著高于乳腺纤维腺瘤组织（P〈0.01）,有淋巴结转移的乳腺癌组织LVD显著高于无淋巴结转移者（P〈0.01）。LVD与年龄、肿瘤大小、ER、PR、c-erbB2无关（P〉0.05）,与病理分期显著相关（P〈0.01）。结论 LVD与乳腺癌的淋巴结转移有关,可作为乳腺癌淋巴结转移的生物学指标。     

乳腺癌淋巴管生成与淋巴结转移、血管内皮生长因子-C表达的关系

目的 探讨乳腺癌中淋巴管生成的分布特点及与血管内皮生长因子-C(VEGF-C)的表达,淋巴结转移和预后的关系.方法 应用免疫组化方法检测70例乳腺癌组织VEGF-C蛋白的表达,并用淋巴管内皮细胞特异性抗体D2-40标记淋巴管,计数肿瘤淋巴管密度(LVD),结合临床病理特征和随访资料进行分析.结果 VEGF-C蛋白的高表达与淋巴结转移(P=0.010)、淋巴管浸润(P=0.031)呈正相关,与肿瘤组织学分级 (P＜0.001) 呈负相关.乳腺癌LVD与淋巴结转移(P＜0.001)、淋巴管浸润(LVI)(P=0.001)、VEGF-C表达(P=0.012)呈正相关,与无病生存率(P=0.011)及总生存率(P=0.001)呈显著负相关.多因素分析显示LVD是影响无病生存率(P=0.015)和总生存率(P=0.002)的独立因子.结论 乳腺癌组织中新生淋巴管主要分布于肿瘤间质,LVD与VEGF-C表达和癌细胞转移相关,乳腺癌微淋巴管密度测定对评估其淋巴结转移和预后判断可能具有意义.