VEGF和CD44v6过表达与乳腺癌浸润转移的关系

目的检测血管内皮生长因子(VEGF)和转移相关黏附分子44v6(CD44v6)在乳腺癌中的表达情况,探讨两者与淋巴结转移的关系。方法采用免疫组化SP法检测92例乳腺浸润性癌中VEGF、CD44v6的表达情况。结果 VEGF在正常乳腺组织和乳腺癌中的阳性表达率分别为6.7%(3/45)和90.2%(83/92),且VEGF在淋巴结转移组中的阳性表达率(53/55)明显高于无淋巴结转移组(P<0.05)。CD44v6在正常乳腺组织及乳腺癌中的阳性表达率分别为8.9%(4/45)和85.9%(79/92),而且CD44v6在淋巴结转移组中的阳性表达率(51/55)明显高于无淋巴结转移组(P<0.05)。VEGF和CD44v6表达呈正相关关系(r=0.497,P<0.05)。结论 VEGF、CD44v6在乳腺癌组织中高表达,且均与淋巴结转移有关(P<0.05),两者可能在乳腺癌的远处转移中起协同作用。     

CD44v6、MT1-MMP和VEGF在肝细胞肝癌中的表达及意义

采用免疫组化法检测40例肝细胞肝癌(简称肝癌)及10例正常肝组织手术切除标本的血管内皮生长因子(VEGF)、黏附分子(CD44v6)和膜型金属蛋白酶-1(MT1-MMP)的表达情况.结果MT1-MMP、CD44v6和VEGF在肝癌组织中阳性表达明显高于正常肝组织(P均＜0.01);MT1-MMP和VEGF与肿瘤的转移、大小有关,与组织分化程度无关;CD44v6与肿瘤的转移、分化程度有关,与大小肿瘤无关;MT1-MMP与CD44v6、CD44v6与VEGF、MT1-MMP与VEGF在肝癌组织中的表达均呈明显正相关(r=0.506、0.701、0.566,P均＜0.01).提示MT1-MMP、CDd4v6、VEGF联合检测有助于肝癌的生物学行为判断和预后评估.     

肝癌组织血管内皮生长因子表达水平的免疫组化研究

目的　旨在研究血管内皮生长因子 (VEGF)与肝癌微血管形成、生长和转移诸方面的关系。方法　对临床 3 6例肝癌术后癌组织 ,以免疫组织化学法研究VEGF在肿瘤组织的胞内分布及其表达 ;并以ELISA法测定癌灶、癌旁及远癌组织中的VEGF蛋白的表达水平。结果　癌组织中VEGF阳性表达率为 63 .9% ;无包膜或包膜不完整组VEGF阳性表达率与有包膜组存在显著差异 ;肝癌伴有远处转移组VEGF阳性表达水平显著高于无转移组 (P <0 .0 1) ,癌灶组织中VEGF的表达水平明显高于癌旁、远癌组织(P <0 .0 1)。结论资料提示VEGF在肝癌组织中高度表达 ,它在HCC的血管形成、肿瘤发展和转移过程中起重要作用 ,提示癌组织中VEGF过度表达是反映肿瘤侵袭生长及转移潜能的有效指标     

KAI1/CD82、VEGF在乳腺癌组织中的表达及临床意义

目的探讨肿瘤转移抑制基因KAI1/CD82和血管内皮生长因子(VEGF)在乳腺癌浸润和转移中的作用。方法采用免疫组织化学SP法检测62例乳腺癌组织中KAI1/CD82和VEGF表达情况,并分析两指标间及与肿瘤临床病理参数的关系。结果 62例乳腺癌组织中KAI1/CD82和VEGF阳性表达率分别为50.00%和62.90%,但两者表达无显著相关;KAI1/CD82在浸润性导管癌组织中的阳性表达率明显低于导管内癌局部浸润者、有淋巴结转移者阳性表达率明显低于无淋巴结转移者,VEGF在临床分期Ⅲ～Ⅳ期乳腺癌组织中的阳性表达率明显高于Ⅰ～Ⅱ期者、在淋巴结转移者中阳性表达率明显高于无淋巴结转移者(P均<0.05)。结论 KAI1/CD82和VEGF均在乳腺癌浸润和转移中起重要作用,此为乳腺癌的临床诊治、预后评估及多靶点治疗提供了新思路。     

PTEN蛋白及CD44V6在中老年NSCLC中的表达及意义

目的研究抑癌基因10q丢失的与张力蛋白同源的磷酸酶(PTEN)基因及CD44V6蛋白在中老年非小细胞肺癌(NSCLC)组织中的表达及意义。方法应用免疫组化染色方法分别检测50例中老年NSCLC组织和18例癌旁组织及20例正常肺组织中PTEN及CD44V6的表达水平。结果正常肺组织及癌旁组织PTEN蛋白阳性表达率明显高于NSCLC组织;高、中分化组明显高于低分化组;临床Ⅰ、Ⅱ期PTEN蛋白阳性率显著高于Ⅲ期;PTEN蛋白表达阳性患者生存率显著高于阴性患者。CD44V6蛋白在正常肺组织中不表达,肺鳞癌和肺腺癌中表达阳性率显著高于癌旁组织。CD44V6在临床Ⅲ期NTCLC中表达显著高于Ⅰ、Ⅱ期;CD44V6表达阳性者患者生存率低。结论PTEN/CD44V6的表达可能在中老年NSCLC的发生、发展和转移过程中扮演着重要的角色。PTEN蛋白表达降低与NSCLC的病理类型、临床分期、预后密切相关。     

颈淋巴清扫术治疗老年舌癌患者的疗效及对CD44V6和MMP-9表达的影响

目的探讨老年舌癌实施颈淋巴清扫术的治疗效果,并观察CD44V6和MMP-9在舌癌组织中的表达。方法采用骨上颈淋巴清扫术治疗老年舌癌患者,并通过免疫组织化学PV9000法观察舌癌和癌旁正常组织中CD44V6和MMP-9的临床表达。结果舌癌中CD44V6的阳性表达率略低于癌旁组织,但无统计学意义(P>0.05);舌癌中MMP-9的阳性表达率明显高于癌旁正常组织(P<0.05);且有颈淋巴结转移组中的舌癌组织CD44V6和MMP-9阳性表达率明显高于无颈淋巴结转移组(P<0.05)。结论采用肩胛舌骨上颈淋巴清扫术治疗舌癌的疗效好,复发率低,舌癌组织中CD44V6和MMP-9的表达和颈淋巴结转移密切相关,可作为评价舌癌颈淋巴结转移和预后的生物学指标。     

肺癌患者血清中可溶性CD44V6含量及组织中CD44V6表达的临床意义

目的 探讨肺癌患者血清中可溶性CD44V6(SCD44V6)蛋白含量及癌组织中CD44V6蛋白表达的临床意义。方法 应用ELISA及免疫组化ABC技术，检测肺癌患者血清中及癌组织内CD44V6，同时与健康人对照。结果 肺癌患者血清中CD44V6含量明显高于健康对照组，术前高于术后，复发转移组高于对照组，CD44V6的血清含量及组织表达与T分期无关，与N分期密切相关。结论 血清中CD44V6含量及组织中CD44V6蛋白表达与肺癌的转移复发有关．可作为一种可靠的判断手术疗效、预后及复发转移的临床检测指标。     

CD15、CD44v6和CD54检测与肝癌复发转移的关系研究

探讨粘附因子CD15、CD44v6和CD54（ICAM-1）在肝细胞癌中的表达及临床意义。利用免疫组织化学染色对51例肝癌手术切除石蜡包埋标本进行CD15、CD44V6、CD54的检测。并结合临床病理指标（Edmondson分级、侵袭转移倾向）进行分析。CD15、CD44v6和CD54在侵袭转移倾向高危组中分别为40%、45%、55%,在低危组中分别为13%、19%、19%;CD15、CD44v6和CD54在HCCⅡ级中分别为10%、20%、20%,在IV级中分别30%、50%、50%。结论：CD15、CD44v6和CD54的异常表达与HCC分期和侵袭转移有关;利用CD15、CD44v6和CD54等预测肝癌的复发转移有可能是一种新的途径。     

胃癌中CD44S和CD44V6的表达及意义

目的　研究胃癌中CD44的表达 ,旨在探讨CD44在胃癌发生发展中的作用及临床意义。方法　采用免疫组化S-P方法检测CD44S及CD44变异体V6在 5 4例胃良性病变 (BGD)及 6 3例胃癌 (GC)中的表达 ,并比较了阳性表达与肿瘤组织分型、淋巴转移等的关系。结果　CD44S在浅表性胃炎 (CSG)、萎缩性胃炎伴肠上皮化生 (CAG/IM)及GC中表达阳性率分别为 46 5 %、5 7 1%、5 2 4%。CD44V6在CSG中无表达 ,在CAG/IM及GC中表达阳性率为 :19 1%和5 3 7%。在有淋巴转移组CD44V6表达率 6 8 6 % ,明显高于无转移组 3 5 7%。在肠型胃癌中 ,CD44V6表达率 73 7% ,明显高于弥漫型胃癌 2 4%。CD44S阳性表达与有否淋巴转移及组织分型无关。结论　CD44S、CD44V6在胃癌中均有表达 ,CD44V6表达率与胃癌淋巴转移及组织来源有关。     

大肠癌组织中CD44V6和MMP-7的表达及临床意义

目的观察大肠癌和癌旁组织中CD44V6和基质金属蛋白酶-7（MMP-7）的表达及其与大肠癌临床病理指标的关系。方法采用免疫组化SP法分别检测大肠癌及癌旁组织中的CD44V6及MMP-7。结果大肠癌组织中CD44V6和MMP-7的阳性表达率分别是84．9％和68．9％,明显高于癌旁组织中的13．2％和8．4％（P〈0．01）。CD44V6和MMP-7的表达与大肠癌组织分化、浸润深度、临床分期及淋巴结转移有关。结论CD44V6和MMP-7与大肠癌侵袭和转移性有关,对分析大肠癌的生物学行为和判断预后有重要意义。     

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

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骨桥蛋白下游信号分子在肝细胞癌中的表达

目的 通过肝癌组织芯片检测骨桥蛋白(OPN)下游的信号蛋白,以确定其在肝癌组织中的信号传导途径.方法构建肝细胞癌组织芯片,用免疫组织化学染色法检测并分析OPN及其相关分子、整合素αV、CD44v6、磷酸化黏着斑激酶(p-FAK)、p-Src、磷酸化细胞外信号调节激酶(p-ERK)、磷酸化蛋白激酶B(p-AKT)的表达水平及其关系.计数资料用卡方检验(或Fisher's确切概率法),各指标之间的相关性采用Spearman相关分析.结果OPN及其受体整合素αV、CD44v6和相关信号分子p-FAK、p-Src、Src、p-ERK、p-AKT在肝癌组织的表达水平均明显高于癌周正常肝组织(P＜0.05).FAK在肝癌和癌周组织中的表达差异无统计学意义(P＞0.05).OPN的表达与整合素oV(P＜0.01)、p-ERK(P＜0.01)、CD44v6(P＜0.05)密切相关,与p-FAK、p-Src、p-AKT无相关性(P＞0.05).但p-FAK(P＜0.05)、p-Src(P＜0.01)和p-AKT(P＜0.05)均与OPN受体整合素αV密切相关,p-FAK还与OPN的受体CD44v6密切相关(P＜0.01).结论 OPN通过其受体整合素αV、CD44v6激活下游的丝裂原活化蛋白激酶途径以促进肝癌转移.

Abstract：

Objective Osteopontin (OPN) has close relationship with metastasis in hepatocellular carcinoma but its downstream signal pathways have not been well defined in hepatocellular carcinoma. The object of this study is to identify the associated signal pathways in human HCC tissues. Methods The expressions of OPN, intergrin α V, CD44v6, P-FAK, FAK, P-Src, Src, P-ERK and P-AKT were assayed using TMA analysis. The relationship of OPN with P-ERK, P-Src and P-AKT were explored and the role in HCC metastasis was analysed. Results The expression levels of OPN, intergrin α V, CD44v6, P-FAK, P-Src, Src, P-ERK and P-AKT in HCC tissue were significantly higher than that in normal tissue (P ＜ 0.05). No significant difference was found between the expression levels of FAK in HCC tissue and normal tissue (P ＞0.05). OPN expression was significantly associated with Integrin α v (P ＜ 0.01 ), CD44V6 (P ＜ 0.01) and P-ERK (P ＜ 0.05) but not with P-Stc, P-FAK and P-AKT (P ＞ 0.05). The expressions of P-FAK (P ＜ 0.05), P-Src (P ＜ 0.01) and P-AKT (P ＜ 0.05) were significantly associated with Integrin α v and the P-FAK expression was also significantly associated with CD44V6 (P ＜ 0.01). Conclusion OPN promotes HCC metastasis though Integrin α v/CD44V6/MAPK pathway in human HCC.     

Recurrence or metastasis of HCC:predictors, early detection and experimental antiangiogenic therapy

AIM To investigate the predictors for recurrence or metastasis of HCC, and to evaluate the effect of antiangiogenic therapy on the growth of transplantable human HCC in nude mice. METHODS RT-PCR was used to measure the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in 56 pairs of nontumorous liver and tumor samples. Sixty blood samples from human HCC were examined by nested RT-PCR to find out AFP mRNA. Recombinant human endostatin and polyclonal antibody against VEGF were administered to treat human HCC transplanted in nude mice. RESULTS Thirty of 56 HCC samples showed stronger expression of MMP-9 in tumorous tissues than in nontumorous tissues. Fifteen of the 26 patients with relative expression level of MMP-9 more than 0.34 developed tumor recurrence or metastasis, whereas only 7 of 30 patients with relative expression level less than 0.34 developed tumor recurrence (P＜0.05).There was no significant difference in the relative expression level of VEGF between patients with postoperative recurrence or metastasis and those without recurrence. AFP mRNA was detectable in 53.3% of patients with HCC. The sensitivity and specificity of AFP mRNA as a marker to detect hematogenous dissemination of HCC cells was 81.8% and 84.4%, respectively. Recombinant human endostatin and polyclonal antibody against VEGF inhibited the growth of transplantable HCC in nude mice by 52.2% and 45.7%, respectively.CONCLUSION MMP-9 expression in HCC correlates with the postoperative recurrence or metastasis of HCC. Patients with high level of MMP-9 expression in HCC are susceptible to metastasis. AFP mRNA could serve as an indicator of hematogenous spreading of HCC cells in circulation and a predictor of recurrence or metastasis of HCC. Antiangiogenesis may be an adjuvant therapy for HCC.     

胃癌及癌前病变组织CD44V6表达的研究

目的:检测细胞粘附分子(CD44V6)在胃癌及癌前病变的表达,探索其与胃癌的发生、转移及预后的相关性.方法:用免疫组化方法检测30例浅表性胃炎,34例中重度萎缩性胃炎、34例不典型增生胃粘膜及64例胃癌组织中的CD44V6的表达.结果:CD44V6的阳性表达率在浅表性胃炎、中重度萎缩性胃炎、不典型增生胃粘膜及胃癌组织分别为3.33%(1/30)、14.71%(5/34)、44.12%(15/34)及60.94%(39/64).不典型增生及胃癌组阳性率明显高于浅表性胃炎组及中重度萎缩性胃炎组(均P＜0.01),中重度萎缩性胃炎与浅表性胃炎组比较差异无统计学意义;CD44V6的表达与胃癌的远处转移有关(P＜0.05),与TNM分期有关(P＜0.01),与淋巴结转移无关,与性别、肿瘤大小、大体类型、组织学分型、浸润深度间差异均无统计学意义.结论:用免疫组织化学方法检测胃活检标本中的CD44V6可能有助于胃癌早期诊断和远处转移趋势推测.     

CD44V6基因在前列腺癌组织中的表达及其意义

目的　探讨CD4 4V6 基因与前列腺癌 (PCa)的发生、转移及预后的关系。方法　采用S P免疫组织化学方法检测 82例PCa组织中CD4 4V6 基因的表达情况。结果　CD4 4V6 基因在前列腺癌中有较高的表达 ,阳性率为 46 3 % (38/82 ) ,其中伴盆腔淋巴结转移或骨转移者阳性率为62 5 % (1 5/2 4 ) ,无转移者阳性率 37 9% (2 3/58) ,两者具有显著性差异 (P <0 0 1 )。CD4 4V6 在PCa组织中的高表达还与癌组织的Gleason评分及预后有关 (P <0 0 5)。结论　具有CD4 4V6 高表达的PCa具有更强的浸润和转移能力 ,恶性度较高 ,分化较差 ,CD4 4V6 可作为判断预后及指导术后治疗的一项重要指标。     

Expression and correlation of CD44v6, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 in Krukenberg tumor

AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: x2 = 4.516, P= 0.034; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 19.537, P= 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 22.895, P= 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 (x2 = 10.398, P= 0.001), VEGF (x2 = 13.149, P= 0.001), MMP-2 (x2= 33.668, P= 0.001) and MMP-9 (x2 = 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.     

Expression and significance of new inhibitor of apoptosis protein survivin in hepatocellular carcinoma

AM: To investigate expression and significance of inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC). METHODS: The expression of survivin and vascular endothelial growth factor (VEGF) was investigated in 38 cases of HCC tissues and 38 liver cirrhosis tissues by immunohistochemistry and Western blot. The relationship between the expression of survivin and clinicopathological factors of HCC was analyzed. RESULTS: Survivin protein was detected in 23 (60.5%) of 38 HCCs and 3 (7.9%) of 38 liver cirrhosis tissues. In 23 cases of HCC which expressed survivin, the expression of VEGF was positive in 18 cases and slight positive or negative in 5 cases. While in 15 cases of HCC which did not express survivin, 12 cases did not express or slightly expressed, and 3 cases expressed VEGF. In liver cirrhosis tissues, the expression of VEGF was as follows: 24 cases were negative, 10 cases were weak positive and 4 cases were strong positive. The expression of survivin was coincident with the expression of VEGF in HCC (P<0.01). The expression of survivin in HCC had no relationship with the patients' age, gender, tumor size and differentiation level of HCC, while it was related to the metastasis of HCC. The protein quantitative analysis by Western blot also showed that overexpression of survivin in HCC was closely correlated to the expression of VEGF (P<0.01). Furthermore, stronger expression of survivin and VEGF was also found in patients with metastasis rather than in those with no metastasis (P<0.01). CONCLUSION: Survivin plays a pivotal role in the metastasis of HCC, and it has some correlation with tumorigenesis. The expression of survivin in the primary lesion is very useful as an indicator for metastasis and prognosis of HCC. It could become a new target of gene therapy of HCC.     

细胞间粘附分子-1在肝癌组织的表达及意义

目的：研究细胞间粘附分子－１（ＩＣＡＭ－１）在原发性肝癌的临床意义。方法：以免疫线化方法结合全自动图像分析检测ＩＣＡＭ－１在３０例原发性肝癌组织及６例正常肝组织的表达,分析其与肿瘤分化程度、大小及转移之间的关系。结果：３０例原发性肝癌组织２５例ＩＣＡＭ－１表达阳性（阳性率８３．３％）,肝癌组织中ＩＣＡＭ－１含量明显高于正常肝组织（Ｐ〈０．０１）,转移组肝癌中ＩＣＡＭ－１含量明显地无转移组（Ｐ〈０．