VEGF-C及受体VEGFR-3在宫颈癌中的表达及临床意义

目的:研究宫颈癌组织中血管内皮生长因子C(VEGF-C)及其受体VEGFR-3的表达并探讨其与淋巴结转移、预后的关系。方法:采用免疫组化SP法,分析59例石蜡标本中VEGF-C、VEGFR-3蛋白表达情况,并应用计算机辅助图象分析系统对脉管的面积进行定量分析。结果:宫颈癌组织中VEGF-C蛋白表达率为66.1%(39/59),与淋巴结转移显著正相关(P=0.005)。VEGF-C阳性组5年生存率显著低于阴性组(P=0.006)。VEGFR-3表达主要定位在脉管结构,VEGFR-3阳性脉管密度在VEGF-C表达阳性组明显高于阴性组(P=0.015),淋巴结转移组明显高于无转移组(P=0.001)。结论:VEGF-C通过促进宫颈癌内淋巴管形成,促进淋巴转移并与患者的预后有关。     

宫颈癌VEGF-C表达和淋巴管、血管生成关系的探讨

目的:检测宫颈癌组织中血管内皮生长因子-C(VEGF-C)、受体VEGFR-3和CD34的表达,探讨VEGF-C与癌周淋巴管、血管生成和肿瘤转移的关系。方法:采用免疫组化法检测55例宫颈癌组织中VEGF-C、VEGFR-3和CD34的表达。结果:55例宫颈癌组织VEGF-C阳性率为69.1%(38/55),VEGFR-3阳性率为61.8%(34/55),二者表达高度一致(P<0.01)。淋巴结转移组中VEGF-C与VEGFR-3阳性表达明显高于无转移组(P<0.05)。低分化组VEGF-C和VEGFR-3的表达明显高于高、中分化组(P<0.05)。随着临床分期增加,VEGFR-3表达的阳性率增高(P<0.01)。淋巴结转移组中淋巴管密度(LMVD)明显高于无转移组(P<0.01)。VEGF-C表达阳性的组织中血管密度(MVD)明显升高(P<0.05)。VEGF-C和VEGFR-3表达阳性的患者生存率有降低的趋势。结论:宫颈癌中VEGF-C通过受体VEGFR-3促进组织生长、抑制分化,促进肿瘤细胞间质淋巴管和血管生成,是促使宫颈癌发生扩散和转移的重要原因。二者阳性表达可预示预后不良。     

血管内皮生长因子C及其受体3在宫颈癌组织中的表达及意义

目的探讨血管内皮生长因子-C(VEGF-C)及其受体3在宫颈癌中的表达及其与癌周淋巴管生成、淋巴结转移的关系。方法采用免疫组化二步法检测55例宫颈癌组织中VEGF-C、VEGFR-3的表达情况。结果宫颈癌组织VEGF-C、VEGFR-3阳性率分别为69.1%、61.8%。VEGF-C与VEGFR-3阳性率在淋巴结转移、低分化组织中均明显升高(均P<0.05)。淋巴结转移的宫颈癌组织中淋巴管密度(LMVD)明显升高(P<0.01)。VEGF-C、VEGFR-3阳性的患者有明显预后不良的趋势。结论VEGF-C通过受体VEGFR-3在宫颈癌发生盆腔淋巴结转移中发挥重要作用。     

VEGFR-3在早期宫颈癌进展过程中的作用

目的:探讨VEGFR-3在早期宫颈癌进展过程中的作用。方法:免疫组织化学法检测41例早期子宫颈癌(ⅠA～ⅡA)组织中VEGF-C、VEGF-D、VEGFR-3的表达,同时检测VEGFR-3标记的脉管密度(MVD),分析其与临床病理因素的关系。结果:(1)VEGFR-3除于淋巴管内皮细胞表达外,部分血管内皮细胞也有表达。形态学上VEGFR-3阳性脉管部分为血管,部分为淋巴管,主要分布于肿瘤组织周围间质中。肿瘤细胞中可见VEGF-C、VEGF-D、VEGFR-3蛋白表达,其表达阳性率分别为48.7%(20/41)、58.5%(24/41)、63.4%(26/41);(2)肿瘤细胞中VEGFR-3蛋白表达与宫颈癌患者月经状态、组织学分级、组织学类型无关,与临床分期、淋巴结转移、淋巴管浸润及VEGF-C、D蛋白表达相关;MVD与月经状态、组织学分级、组织学类型、淋巴结转移、淋巴管浸润均无关,与临床分期及VEGF-C、D蛋白表达相关。结论:VEGFR-3可能通过促进肿瘤血管生成和淋巴管生成,参与了早期宫颈癌的恶性进展。     

胰岛素样生长因子1受体和血管内皮生长因子C表达及其与宫颈癌淋巴结转移的关系

目的 研究宫颈癌中胰岛素样生长因子1受体(IGF-1R)和血管内皮生长因子C（VEGF-C）的表达及其与淋巴结转移关系。方法 选取河南科技大学第一附属医院2008年9月至2011年5月50例宫颈鳞癌组织为研究组,30例正常宫颈组织为对照组,应用SP免疫组化法研究IGF-1R、VEGF-C的表达情况。结果 研究组淋巴结转移与IGF-1R、VEGF-C阳性表达有关(P< 0.05)。D2-40标记的淋巴管密度（LVD）在IGF-1R、VEGF-C阳性表达组明显高于阴性组,且两者的阳性表达在研究组呈正相关。结论 IGF-1R、VEGF-C的表达与宫颈癌的淋巴转移有关,对于早期判断淋巴结转移有一定价值,联合检测二者有助于判断预后,指导临床治疗。     

血管内皮生长因子-C与乳腺癌淋巴管生成及淋巴转移的相关性研究

目的:研究血管内皮生长因子-C与乳腺癌淋巴管生成的关系,探讨其在乳腺癌淋巴转移中的作用。方法:以免疫组化SP法分别检测41例乳腺癌组织及周围正常组织、有、无转移淋巴结组织中的VEGF-C蛋白的表达水平,并采用实时定量PCR法检测乳腺癌组织、周围正常组织VEGF-CmRNA的表达水平,探讨其在乳腺癌淋巴转移中的作用。结果:VEGF-C在乳腺癌组织中和在周围正常乳腺组织中的阳性表达率分别为78.0%和34.1%;在淋巴结转移组中和无转移淋巴结组中阳性率分别为61.9%和30.0%和25.0;2组差别均有统计学意义(P<0.01)。结论:乳腺癌细胞可能通过VEGF-C的高表达刺激新生淋巴管的生成,诱导肿瘤细胞进入淋巴管中,以促进乳腺癌淋巴转移的发生。     

IGF-IR在宫颈癌和淋巴结转移组织中表达的临床意义

目的:研究宫颈癌和淋巴结转移组织中胰岛素样生长因子Ⅰ受体(insulin- like growth factor-Ⅰreceptor,IGF-IR)的表达及其与淋巴结转移、预后的关系。方法:用免疫组化S-P法检测IGF-IR在46例宫颈癌、12例正常宫颈组织和22例转移淋巴结组织中的表达。结果:宫颈癌组织中IGF-IR蛋白表达率为45．7%(21/46),转移淋巴结组织中阳性率为45．5%(10/22),分别高于良性组织;淋巴结转移组原发灶中IGF-IR蛋白表达率明显高于无转移组原发灶中的表达(x~2=5．497,P=0．019)。结论:宫颈癌广泛存在IGF- IR蛋白过表达,检测IGF-IR蛋白表达可能有助于判断宫颈癌的预后,并可能为判断宫颈癌生物学行为提供有意义的指标。     

血管内皮生长因子C及其受体3mRNA在上皮性卵巢癌组织的表达及意义

目的 探讨血管内皮生长因子C（VEGF-C）及其受体3（VEGFR-3）mRNA在上皮性卵巢癌组织的表达及与癌周淋巴管生成及淋巴转移的关系。方法 2003-04—2004-06第三军医大学附属西南医院采用RT-PCR方法，检测VEGF-C及VEGFR-3mRNA在良、恶性上皮性卵巢肿瘤组织的表达及组织化学淋巴管染色并计数，分析其与VEGF-C mRNA表达及淋巴转移的关系。结果 VEGF-C mRNA和VEGFR-3 mRNA在卵巢良、恶性肿瘤的表达差异有显著性。VEGF-C mRNA表达阳性及有淋巴结转移组的癌组织淋巴管密度分别大于VEGF-CmRNA表达阴性及无淋巴结转移组的癌组织，二者差异均有显著性。结论 VEGF-CmRNA在上皮性卵巢癌组织的表达上调导致了癌周淋巴管生成，促进了肿瘤的淋巴道转移。     

MACC1、c-Met蛋白在宫颈癌中的表达及与盆腔淋巴结转移的关系研究

目的:探讨结肠癌转移相关基因1(MACC1)、肝细胞生长因子受体(c—Met)蛋白在宫颈癌中的表达及与盆腔淋巴结转移的关系。方法:采用免疫组织化学检测10例正常宫颈组织、17例中~重度宫颈上皮内瘤变组织(CINⅡ~Ⅲ)和91例宫颈癌组织中MACC1、c—Met蛋白的表达情况,分析两者在宫颈癌组织中表达的相关性及与宫颈癌盆腔淋巴结转移的关系。结果:MACC1、c—Met蛋白在宫颈癌组织、CINⅡ~Ⅲ组织中的阳性表达率分别依次为83.5%、76.5%,80.2%、70.6%,均显著高于正常宫颈组织(P0.05)。宫颈癌中MACC1蛋白的表达与c—Met蛋白的表达呈正相关(r=0.672,P0.05)。将宫颈癌盆腔淋巴结转移组与无转移组进行单因素比较分析,MACC1蛋白表达、c-Met蛋白表达、组织学分化程度、脉管浸润、肌层浸润深度与宫颈癌盆腔淋巴结转移有关(P0.05),进一步Logistic回归分析表明,MACC1蛋白表达、肌层浸润深度是宫颈癌盆腔淋巴结转移的独立危险因素(P0.05)。结论:MACC1、c-Met蛋白异常表达可能协同参与宫颈癌的恶性进展,MACC1蛋白高表达是宫颈癌盆腔淋巴结转移的独立危险因素。     

血管内皮生长因子C的表达与宫颈癌的关系

血管内皮生长因子C(VEGF-C)是近几年发现的VEGF家族的新成员,主要通过与其受体VEGFR-3(Flt4)和VEGFR-2(Flk1)结合,促进淋巴管、血管的生成及肿瘤细胞转移.在淋巴结转移阳性的宫颈癌患者中其表达显著增强,且与宫颈癌的侵袭表型、生存率密切相关,可作为判断预后的独立因素.VEGF-C的发现为宫颈癌治疗提供了新思路.     

Expression of vascular endothelial growth factors (VEGF-A/VEGF-1 and VEGF-C/VEGF-2) in postmenopausal uterine endometrial carcinoma

OBJECTIVE: We investigated the expression of two angiogenic vascular endothelial growth factors, VEGF-A/VEGF-1 and VEGF-C/VEGF-2, in 228 cases of uterine endometrial carcinomas from postmenopausal patients to evaluate the correlation with histopathologic features and clinical outcome. METHODS: Immunohistochemistry was used to assess VEGF-A/VEGF-1 and VEGF-C/VEGF-2 expression in 228 primary surgically treated cases of postmenopausal endometrial carcinomas and the results were statistically analyzed in relation to vascular invasion, depth of invasion (myometrial vs serosal-parametrial invasion), lymphatic vessel invasion, lymph node metastasis, disease-free 5-year survival rate (DF5YR), and disease-free 10 year-survival rate (DF10YR). RESULTS: The results of univariate analysis showed that VEGF-A/VEGF-1 and VEGF-C/VEGF-2 expression correlated with vascular invasion (P < 0.0001, P = 0.0006), depth of invasion (P = 0.0004, P = 0.043), lymphatic vessel invasion (P = 0.021, P < 0.0001), lymph node metastasis (P = 0.0017, P = 0.0008), DF5YR (P = 0.0081, P = 0.0002), and DF10YR (P = 0.0077, P = 0.0001). Multivariate analysis showed that lymph node metastasis (P = 0.0017, P = 0.0008), parametrial-serosal invasion (P < 0.0001, P < 0.0001), and VEGF-C/VEGF-2-positive status (P = 0.03, P = 0.01) were significant factors in DF5YR and DF10YR. CONCLUSIONS: We conclude that VEGF-A/VEGF-1 and VEGF-C/VEGF-2 expression was predictive of these histopathologic features of endometrial carcinoma and clinical outcome.     

Fas ligand expression in cervical adenocarcinoma: relevance to lymph node metastasis and tumor progression

OBJECTIVE: Adenocarcinoma of the cervix carries a worse prognosis than its squamous counterpart. In particular, tumors with lymph node metastasis have a miserably poor prognosis. Fas ligand (FasL) could allow the tumor cells to evade host immune surveillance and would thus promote tumor survival and possibly metastasis formation. We decided to compare FasL expression in cervical adenocarcinoma with lymph node status to determine whether FasL plays a role in lymph node metastases. METHODS: Using immunohistochemistry, we investigated FasL expression in sections of formalin-fixed, paraffin-embedded tissue from 24 cervical adenocarcinomas. We also studied sections of seven cases with lymph node metastases. The percentage of FasL-positive cells in each tumor was recorded. FasL expression in cervical adenocarcinoma was compared with lymph node status. Statistical analysis was performed by using the Fisher exact test and the Kaplan-Meier method. RESULTS: FasL expression was detected in 62.5% (15 of 24) of primary lesions. Significantly higher incidence of positive FasL reactivity was demonstrated in 10 of 11 tumors with lymph-vascular space (P = 0.0188), in 10 of 10 with deep stromal invasion (P = 0.0015), and in 8 of 9 cancers with lymph node metastasis (P = 0.0481). All 9 metastatic cervical adenocarcinoma in the lymph nodes showed FasL immunoreactivity in 60.7 +/- 17.7% of the metastatic cancer cells, and 7 (78%) of these had FasL immunoreactivity in greater than 50% of the cells. The survival times of patients with FasL-expressing cervical adenocarcinomas were significantly reduced compared to patients with low FasL-expressing tumors (P = 0.0018). CONCLUSIONS: These findings indicate that FasL plays an important role in immune evasion, and progression and metastasis of cervical adenocarcinoma.     

Expression of IGF-1R, VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma

Insulin-like growth factor-1 receptor (IGF-1R) regulates carcinogenesis and tumor development and is expressed in normal endometrium. Vascular endothelial growth factor C (VEGF-C) promotes lymph node metastasis. We investigated IGF-1R, VEGF-C and D2-40 in endometrial adenocarcinoma and the association between IGF-1R and lymphatic metastasis, using an immunohistochemical S-P method with 40 cases of endometrial adenocarcinoma and 14 of normal endometrium. IGF-1R expression differed significantly between normal endometrium and adenocarcinoma; it was associated with histological grade but not surgical stage. IGF-1R overexpression was associated with metastasis, but expression was not. VEGF-C expression was greater in normal endometrium than in adenocarcinoma and was associated with metastasis but not with surgical stage or histological grade. IGF-IR and VEGF-C expression were correlated in endometrial adenocarcinoma, and lymphatic vessel density was closely related to both. Abnormal IGF-IR and VEGF-C expression may be important in lymph node metastasis of endometrial adenocarcinoma and might be used to evaluate the prognosis.     

Expression of cyclooxygenase-1 and -2 associated with expression of VEGF in primary cervical cancer and at metastatic lymph nodes

OBJECTIVES: This study examines the relationship between expression of COX-1, COX-2, and vascular endothelial growth factor (VEGF), and their association with clinicopathological features in primary tumor and metastatic lymph node specimens from cervical cancer patients. The relationship between COX-2 expression and human papillomavirus (HPV) positivity was also examined. METHODS: The following samples were analyzed: 97 paraffin-embedded specimens from patients with cervical cancer (Ib-IIb), including 49 primary cervical cancer specimens without lymph node metastasis and 24 primary specimens with lymph node metastasis and their metastatic lymph nodes. Immunohistochemical analysis was performed with antibodies to COX-1, COX-2, and VEGF. HPV viratype was identified by PCR and HPVDNAChip. RESULTS: VEGF expression was strongly correlated with expression of COX-1 (P = 0.03) and not COX-2 (P = 0.12) in primary tumor and metastatic lymph nodes. COX-2 expression correlated with lymph node metastasis (P = 0.001), but not with any other clinicopathological features. The parametrial invasion showed borderline significance with COX-2 expression (P = 0.058). COX-1 or VEGF expression did not correlate with any clinicopathological features. In addition, COX-2 expression was not associated with HPV positivity.COX-1 expression is associated with VEGF expression in primary tumor tissue and at sites of metastasis to lymph nodes. CONCLUSION: COX-2 expression is associated with lymph node metastasis and possibly parametrial invasion, but expression of COX-1 and VEGF is not associated with clinicopathological features. COX-2 expression is not associated with HPV positivity.     

髓系细胞触发受体-1在人卵巢癌组织中的表达及其与淋巴结转移的相关性研究

目的:通过检测髓系细胞触发受体-1(TREM-1)在人卵巢癌组织中的表达及其与淋巴转移的相关性,探讨其参与调控肿瘤相关性炎症的可能机制。方法:选择2010年10至2011年10月南昌大学第一附属医院收治的卵巢癌患者30例与卵巢良性肿瘤患者20例。免疫组织化学法测定TREM-1在卵巢癌和卵巢良性肿瘤组织中的表达;用CD163标记M2型肿瘤相关巨噬细胞(TAMs);用D2-40标记微淋巴管,计算微淋巴管密度(LMVD)。分析TREM-1表达与卵巢癌临床病理资料的相关性。结果:卵巢癌组织中TREM-1蛋白的阳性表达率为100%,强阳性表达率为70%(21/30),阳性率显著高于卵巢良性肿瘤的10.0%(2/20)(χ2=42.19,P=0.000)。卵巢良性肿瘤组织中TREM-1和CD163很少表达。TREM-1定位于TAMs。TREM-1表达强度与淋巴转移存在相关性(P=0.01)。Logistic回归分析示,TREM-1评分是淋巴结转移的危险因素(P=0.009)。结论:TREM-1表达于卵巢癌组织的TAMs,其调控的炎症可能在促进卵巢癌淋巴转移中起着重要作用。