乳腺癌组织中趋化因子受体CCR7的表达及其意义

目的：检测乳腺癌中趋化因子受体CCR7的表达及其临床意义。方法：收集65例根治性切除的乳腺癌标本,用免疫组织化学法检测CCR7的表达,分析CCR7的表达与乳腺癌患者临床病理特征之间的相关性。结果：65例标本中,42例存在CCR7的高表达（64.6%）,CCR7的表达与乳腺癌患者的淋巴结转移、TNM分期和肿瘤组织中淋巴细胞的浸润程度密切相关,但与淋巴结转移的数目无关。结论：趋化因子受体CCR7与乳腺癌淋巴结转移密切相关,其在乳腺癌的临床诊治中有参考价值。     

非小细胞肺癌中D2-40、CCR7的表达与淋巴结转移的关系

 目的探讨CCR7 及D2-40在非小细胞肺癌中的表达与淋巴结转移的关系。方法采用快捷免疫组织化学 Max Vision法检测104例非小细胞肺癌、10例非小细胞癌旁组织及5例正常肺组织CCR7和D2-40的表达,并 以D2-40标记淋巴管内皮细胞,计算微淋巴管密度(MLVD)。结果非小细胞肺癌与正常肺组织MLVD计数分别 为(7.81±2.22)、(4.20±1.07),非小细胞肺癌中MLVD明显增高（P<0.001）。非小细胞肺癌中47例淋巴 结阳性组与57例淋巴结阴性组MLVD计数分别为(8.39±2.35)、(7.33±2.00),淋巴结阳性组MLVD计数显著 高于淋巴结阴性组（P<0.001）。104例非小细胞肺癌CCR7阳性率为82.7%;癌旁肺组织CCR7阳性率为30% ;正常肺组织CCR7阳性率为20%。淋巴结阳性组与淋巴结阴性组CCR7阳性率分别为872%（41/47）、 61.4%（35/57）。χ2值为87.4,P值为0.03。CCR7阳性组MLVD（8.51±2.03）高于CCR7阴性组MLVD（6.01 ±1.59）,两者比较差异具有统计学意义(P<0.05)。D2-40标记的MLVD与CCR7表达呈正相关（相关系数 r=0.597,P<0.000）。结论在非小细胞肺癌中,淋巴结阳性组CCR7高表达,与D2-40标记的MLVD正相关。 D2-40仅表达于淋巴管内皮细胞,且肿瘤细胞CCR7高表达属淋巴结转移早期事件,联合检测CCR7与D2-40有 望成为判断淋巴结转移更为有效的指标。并可能为今后治疗非小细胞肺癌及抑制淋 巴结转移提供有力的理论依据。     

舌癌转移淋巴结中舌癌细胞耐药性的实验研究

目的:观察舌癌淋巴结转移模型中舌癌细胞耐药特性,探讨舌癌转移与耐药相关性。方法:在建立舌癌淋巴结转移模型的基础上,取淋巴结转移的舌癌细胞进行HE染色与免疫组化检测P-gp和LRP耐药相关蛋白,并分离纯化其细胞进行耐药特性检测,包括半数抑制浓度(IC50)、耐药倍数(re-sistance index,RI)与细胞内多柔比星荧光强度。结果:转移淋巴结中舌癌细胞表达P-gp和LRP蛋白,其分离纯化的子代细胞对多柔比星IC50为(1.86±0.026)μg/mL,对照的亲本(Tca8113)舌癌细胞IC50为(0.26±0.005)μg/mL,RI为7.15;进一步检测淋巴结转移舌癌细胞内多柔比星浓度,其多柔比星荧光强度为6.13±2.48,明显低于亲本Tca8113舌癌细胞的12.36±3.59,P<0.05。结论:淋巴结转移的舌癌细胞有一定的耐药特性。     

趋化因子受体CCR7在胃癌组织和细胞株中过度表达（摘要）

背景趋化因子受体CCR7高表达与肿瘤淋巴结转移等因素密切相关。目的检测CCR7在胃癌组织和细胞株中的表达情况,探讨CCR7在胃癌中的作用。方法采用实时PCR技术检测30例胃癌组织及其配对癌旁组织中的CCR7mRNA表达,     

非小细胞肺癌淋巴结分子分期的对照研究

背景与目的：影响非小细胞肺癌患者术后生存时间的主要因素是其临床病理分期。令人费解的是目前肿瘤复发在Ⅰ期肺癌中并不少见。本研究旨在探讨部分非小细胞肺癌患者常规病理分期是否存在偏低现象。方法：术中采集25例非小细胞肺癌患者淋巴结共195枚,每枚淋巴结平均分成两半。一半淋巴结进行苏木精伊红染色和免疫组织化学染色;另一半淋巴结按区域混合,用于逆转录聚合酶链反应。结果：195枚淋巴结作了苏木精伊红染色病理检查,其中30枚淋巴结发现有显性转移：无一枚淋巴结检出微转移。135枚苏木精伊红染色阴性的淋巴结作了免疫组织化学染色,其中31枚淋巴结中检出微小转移的肿瘤细胞;无一枚淋巴结检出显性转移。39组苏木精伊红染色阴性的区域淋巴结混合组织中,11组逆转录聚合酶链反应呈阳性。免疫组织化学染色和逆转录聚合酶链反应检测肺癌淋巴结微转移的结果存在一致性（U=7．682,P〈0．001）。结论：苏木精伊红染色能准确地检测出肺癌患者淋巴结中的显性转移灶,而不易发现隐匿性微转移灶。免疫组织化学染色能够提高肺癌患者淋巴结微转移的检出率。逆转录聚合酶链反应在检测肺癌淋巴结微转移方面,与免疫组织化学染色价值相当。     

L1细胞黏附分子在非小细胞肺癌组织中的表达及意义

目的探讨L1细胞黏附分子(L1CAM)在非小细胞肺癌组织中的表达及临床意义。方法选取2013年2月至2014年2月间鄂东医疗集团市中心医院收治的50例非小细胞肺癌患者,采集患者癌组织与癌旁组织标本各50例,采用免疫组织化学SP法检测癌组织与癌旁组织中的L1CAM表达阳性率情况。分析非小细胞肺癌组织中L1CAM表达情况与临床病理参数的关系。对患者进行3年随访,根据存活情况分为存活组19例和死亡组31例,比较两组患者的L1CAM表达阳性率情况。结果非小细胞肺癌组织中L1CAM阳性表达率明显高于癌旁正常组织,组间比较,差异有统计学意义(P<0.05)。非小细胞肺癌中,鳞癌、TNM分期为Ⅲ~Ⅳ期、有淋巴结转移及术后转移患者组织中的L1CAM阳性表达率均明显高于腺癌、TNM分期为Ⅰ~Ⅱ期、无淋巴结转移及无术后转移患者组织,组间比较,差异均有统计学意义(均P<0.05)。3年随访后,存活组患者组织中的L1CAM阳性表达率明显低于死亡组,组间比较,差异有统计学意义(P<0.05)。结论 L1CAM可能在非小细胞肺癌发生、发展、侵袭及转移过程中发挥至关重要的作用,可作为临床诊断和预后评估的指标之一。     

食管鳞状细胞癌中热休克蛋白10和60的表达及其意义

目的探讨食管鳞状细胞癌中热休克蛋白(HSP)10、60的表达及其意义。方法应用免疫组化:EnVision二步法,观察168例食管鳞状细胞癌和42例切缘食管黏膜中HSP10、60的表达,并比较其阳性率。结果 HSP10在食管鳞状细胞癌和切缘食管黏膜表达率分别为53．8％和 37．5％,统计学分析结果表明差异无显著意义(P>0．05);HSP60在食管鳞状细胞癌和切缘食管黏膜表达率分别为92．7％和63．2％,统计学分析结果表明差异有显著意义(P<0．01)。在高、中、低分化食管鳞状细胞癌中HSP10、60的表达差异均无显著意义(P>0．05),两者的表达与食管鳞状细胞癌区域淋巴结转移无关(P>0．05)。结论 HSP60在食管鳞状细胞癌的表达高于切缘食管黏膜,提示其在食管鳞状细胞癌的发生发展中起作用。HSP10、60的表达与食管鳞状细胞癌分化程度、区域淋巴结转移无关。     

人高、低转移大细胞肺癌细胞株中黏附分子存在状态的鉴定

目的:鉴定人高、低转移大细胞肺癌细胞株L9981和NL9980中黏附分子的存在状态。方法:利用半定量RT-PCR技术检测人高、低转移大细胞肺癌细胞株L9981和NL9980中E-cadherin、integrinβ1、integrinβ3基因的mRNA表达;利用流式细胞仪技术检测人高、低转移大细胞肺癌细胞株L9981和NL9980中E-cadherin、integrinβ1、integrinβ3基因的蛋白表达。结果:人高转移大细胞肺癌细胞株L9981中E-cadherin mRNA与蛋白表达水平显著低于低转移大细胞肺癌细胞株NL9980,而integrinβ1和integrinβ3的mRNA与蛋白表达水平高转移L9981细胞株显著高于低转移NL9980细胞株。结论:E-cadherin高表达与肺癌低转移有关,而integrinβ1、integrinβ3高表达与肺癌高转移有关。     

食管鳞状细胞癌中p16、PCNA表达研究

[目的]通过对食管鳞状细胞癌组织中p16与增殖细胞核抗原(PCNA)蛋白表达的研究,探讨二者与食管鳞状细胞癌生物学行为的关系.[方法]检测49例经术后病理证实的食管鳞状细胞癌患者p16与PCNA在不同的病理分级及有无淋巴结转移组中的表达,使用SPSS10.0软件进行统计分析.[结果](1)p16蛋白的阳性细胞面积比率及阳性强度均值在无淋巴结转移组(71.92%,8.38)明显高于淋巴结转移组(60.04%,6.64),P＜0.05.(2)PCNA蛋白的阳性细胞面积比率及阳性强度均值在无淋巴结转移组(42.77%,11.63)明显低于淋巴结转移组(74.67%,15.08),P＜0.01.(3)p16蛋白阳性细胞面积比率及阳性强度均值随病理分级的升高而降低(Ⅰ级79.67%,10.94;Ⅱ级57.50%,9.13;Ⅲ级45.29%,6.889),P＜0.01.(4)PCNA蛋白阳性细胞面积比率及阳性强度均值随病理分级的升高而升高(Ⅰ级38.50%,10.41;Ⅱ级63.63%,13.38;Ⅲ级78.00%,16.13),P＜0.01.[结论]测定p16及PCNA可能对食管鳞状细胞癌的诊断,淋巴结浸润、侵袭及转移,恶性度的判定及治疗有重要作用.     

缺氧诱导因子和细胞黏附分子在胰腺癌中表达及临床意义

目的：了解胰腺癌中缺氧诱导因子-1α（hypoxia-induciblefactor-1α，HIF-1α）与E-钙黏素（E-cadherin）、整合素β1（in-tegrinβ1）的表达关系，探讨HIF-1α促进胰腺癌侵袭转移的机制及临床意义。方法：用免疫组织化学法检测34例胰腺癌和10例正常胰腺组织中HIF-1α、E-cadherin和integrinβ1的表达，分析HIF-1α和E-cadherin、integrin β1的表达之间的相关性及与临床病理特征的关系。结果：胰腺癌组织存在HIF-1α过表达、E-cadherin异常表达和integrinβ1高表达。HIF-1α与E-cadherin的表达呈负相关，与integrinβ1无关；HIF-1α表达与病理分期、淋巴转移有关，E-cadherin异常表达与肿瘤分化、病理分期和淋巴转移有关，integinβ1与临床病理特征无关。结论：HIF-1α可能通过调节E-cadherin异常表达促进胰腺癌侵袭转移，免疫组织化学检测HIF-1α和E-cadherin对判断胰腺癌恶性潜能可能有一定的价值。     

Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer.

BACKGROUND: The chemokine receptors CXCR4 and CCR7 have been suggested to play an important role in cancer invasion and metastasis. The expression of these receptors in human cervical cancer, however, has seldom been characterized. PATIENTS AND METHODS: We investigated the expression of CXCR4 and CCR7 in cervical cancer specimens and determined the association between their expression and the clinicopathological features observed, including patient outcome. RESULTS: CXCR4 expression was significantly higher in elderly patients (P=0.025); it was also significantly increased in patients with cancers displaying large tumor size (P=0.010), deep stromal invasion (P=0.0004), lymph-vascular space involvement (P=0.0002), or lymph node metastasis (P<0.0001). CCR7 expression was significantly higher in cases of squamous cell carcinomas (P=0.010) and in patients with cancers showing large tumor size (P<0.0001), deep stromal invasion (P<0.0001), vaginal invasion (P=0.047), lymph-vascular space involvement (P=0.012), or lymph node metastasis (P<0.0001). Logistic regression analysis revealed that deep stromal invasion (P=0.017) and CXCR4 (P=0.016) and CCR7 (P=0.022) expression were independent factors that influenced pelvic lymph node metastasis. The disease-free survival and overall survival (OS) rates of patients exhibiting both CXCR4 and CCR7 expression were significantly reduced (P<0.0001). In addition, the expression of both CXCR4 and CCR7 was an independent prognostic factor for OS (95% confidence interval=1.03-17.86; P=0.046). CONCLUSIONS: CXCR4 and CCR7 expression may be associated with lymph node metastasis; moreover, the expression of these receptors can serve as an indicator of poor prognosis in patients with cervical cancer.     

Autocrine and paracrine loops between cancer cells and macrophages promote lymph node metastasis via CCR4/CCL22 in head and neck squamous cell carcinoma

Lymph node metastasis is a poor prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). However, its molecular mechanism has not yet been fully understood. In our study, we investigated the expression of CCR4 and its ligand CCL22 in the HNSCC tumor microenvironment and found that the CCR4/CCL22 axis was involved in lymph node metastasis of HNSCC. CCR4 was expressed in 20 of 31 (64.5%) human tongue cancer tissues, and its expression was significantly correlated with lymph node metastasis (p < 0.01) and lymphatic invasion (p < 0.05). CCR4 was expressed in three of five human HNSCC cell lines tested. CCR4⁺ HNSCC cells, but not CCR4^? cells, showed enhanced migration toward CCL22, indicating that functional CCR4 was expressed in HNSCC cell lines. CCL22 was also expressed in cancer cells (48.4% of tongue cancer tissues) or CD206⁺ M2‐like macrophages infiltrated in tumors and draining lymph nodes. CCL22 produced by cancer cells or CD206^high M2‐like macrophages increased the cell motility of CCR4⁺ HNSCC cells in vitro in an autocrine or paracrine manner. In the mouse SCCVII in vivo model, CCR4⁺ cancer cells, but not CCR4^? cells, metastasized to lymph nodes which contained CCL22 producing M2‐like macrophages. These results demonstrate that lymph node metastasis of CCR4⁺ HNSCC is promoted by CCL22 in an autocrine or M2‐like macrophage‐dependent paracrine manner. Therefore, the CCR4/CCL22 axis may be an attractive target for the development of diagnostic and therapeutic strategies for patients with HNSCC.     

弥散加权成像对于鉴别舌鳞癌转移淋巴结的价值

目的探讨弥散加权成像(DWI)对于鉴别舌鳞癌转移与非转移淋巴结的价值。方法收集2011年4月1日至2011年11月30日在中山大学肿瘤防治中心初治42例舌鳞癌患者,治疗前行常规MRI及DWI检查,观察并比较舌鳞癌转移淋巴结与非转移淋巴结常规MRI及表观扩散系数(ADC)图表现,测量各淋巴结的长径(L)、横径(S)、T2信号强度、平均ADC值,采用独立样本t检验及χ2检验比较两者差异,利用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析,评价上述各项指标鉴别舌鳞癌及转移与非转移淋巴结的诊断效能。结果转移淋巴结短径(S)、长径(L)、平均ADC值与非转移淋巴结比较,两者差异有统计学意义(P<0.05);DWI和常规MRI术前诊断出的转移肿大淋巴结与术后病理比较差异均无统计学意义(均P>0.05);转移淋巴结S/L、T2信号强度与非转移淋巴结间的差异无统计学意义(P>0.05)。ROC曲线面积分析淋巴结ADC值曲线下面积最大,诊断淋巴结阳性准确度最高。结论在常规影像学基础上,定量分析测量ADC值有助于舌鳞癌转移和非转移淋巴结的检出。     

胃中部癌前哨淋巴结邻近、横向和跳跃性转移的临床分析

Objective: To investigate the distribution pathway of sentinel lymph nodes (SLN) in middle third gastric carci-noma, as the foundation for rational lymphadenectomy. Methods: 52 cases of middle third tumors with solitary lymph nodes from 1852 gastric carcinomas were selected. The locations and histological types of metastatic lymph nodes were analyzed retrospectively. Results: Of 52 solitary node metastases cases, 37 were limited to perigastric nodes (N1), while 15 with skipping metastasis. In the 35 cases with tumor of lesser curvature, there were 17 cases found lymph nodes of the lesser curvature side (No. 3), 5 cases involved lymph nodes of the greater curvature (No. 4), and 8 cases with lymph nodes of the left gastric artery (No. 7). In the 17 cases with tumor of greater curvature, 7 cases spread to No. 4, while 3 metastasized to lymph nodes of the spleen hilum (No. 10). The difference of the histological types in groups N1 and over N1, were not statistically significant (P > 0.05). Conclusion: Adjacent metastasis formed the primary distribution pattern of SLN in middle third gastric carcinoma, transversal and skipping metastases being also notable.     

前哨淋巴结活检在胃癌根治术中的应用

目的：探讨前哨淋巴结活检（SLNB）在胃癌根治术中临床应用的可行性及其价值。方法：应用美蓝对55例胃癌患者行SLN定位活检,分体内、体外组,采用HE染色病理检查法、CK20免疫组化染色检测SLN中转移癌。结果：共检出淋巴结560枚,其中SLN 262枚,检出率85.7%。免疫组化学法检测SLN癌转移的敏感性明显高于HE染色,而假阴性明显低于后者（P〈0.05）。结论：胃癌根治术中行前哨淋巴结活检技术,具有切实的可行性,能够预测区域淋巴结的转移状况;通过IHC法检查有助于明确胃癌的病理分期,有利于判断预后和个体化治疗方案的制定。     

CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels

Chemokines are a family of cytokines that mediate leukocyte trafficking and are involved in tumor cell migration, growth, and progression. Although there is emerging evidence that multiple chemokines are expressed in tumor tissues and that each chemokine induces receptor‐mediated signaling, their collaboration to regulate tumor invasion and lymph node metastasis has not been fully elucidated. In this study, we examined the effect of CXCL12 on the CCR7‐dependent signaling in MDA‐MB‐231 human breast cancer cells to determine the role of CXCL12 and CCR7 ligand chemokines in breast cancer metastasis to lymph nodes. CXCL12 enhanced the CCR7‐dependent in vitro chemotaxis and cell invasion into collagen gels at suboptimal concentrations of CCL21. CXCL12 promoted CCR7 homodimer formation, ligand binding, CCR7 accumulation into membrane ruffles, and cell response at lower concentrations of CCL19. Immunohistochemistry of MDA‐MB‐231–derived xenograft tumors revealed that CXCL12 is primarily located in the pericellular matrix surrounding tumor cells, whereas the CCR7 ligand, CCL21, mainly associates with LYVE‐1⁺ intratumoral and peritumoral lymphatic vessels. In the three‐dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21‐reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand–expressing intratumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.     

前哨淋巴结识别在早期宫颈癌临床应用的研究进展

宫颈癌在女性生殖器官肿瘤中发病率最高,淋巴结转移是其细胞转移的最早特征,宫颈癌患者局部淋巴结状况直接影响患者的预后并决定着辅助治疗方案的制定。前哨淋巴结是在原发肿瘤淋巴引流区域内,淋巴结发生转移必经的首站淋巴结。前哨淋巴结(SLN)能反映整个盆腔淋巴结的转移状况。其研究使大多数早期宫颈癌患者避免不必要的盆腔淋巴结清扫术。