胃癌及淋巴结转移灶中 CD44v5、 CD44v6 和上皮钙粘素的表达及意义

目的：探讨CD44v6、CD44v6和上皮钙粘素（epithelial cadherin,E-cd)在胃腺癌及淋巴结转移灶中的表达及其意义。方法：应用免疫组化SABC法检测20例正常胃粘膜、20例胃粘膜上皮异形增生组织、185例胃癌原发灶及117例淋巴结转移灶中CD44v5、CD44v6和E－cd表达。结果：CD44v5、CD44v6和E-cd在胃粘膜异型增生的阳性表达率依次为10．0％（2／20）、20．0％A（4／20）和85．0％（17／20）。胃癌原发灶及淋巴结转移灶中其阳性表达率依次分别为43．8％（84／185）、66．5％（123／185）、53．0％（98／185）和71．8％（84／117）、87．2％（102／117）、26．5％（31／117）。三者之间有显著差异（P＜0．01）。CD44v5阳性表达与胃癌生长方式、组织学类型、血管淋巴管内浸润及TNM分期密切相关,而CD44v6遇上述因素在统计学上则无显著性差异（P＞0．05）。E－cd阳性表达与胃癌生长方式、组织学类型及TNM分期显著相关。早期肠型胃癌CD44v6阳性表达率显著高于弥漫性（P＜0．05）。而在进展期胃癌,CD44v5的阳性表达则同弥漫性胃癌显著相关（P＜0．05）,E－cd的阳性表达率下降主要见于弥漫型胃癌。结论：CD44v5、CD44v6和E－cd阳性表达同胃癌分化及生物学行为密切相关,是预测其侵袭转移的价值指标。同时,此结果也支持胃癌两种不同起源的假说。     

E—钙黏附素和基质金属蛋白酶—2的表达变化及与胃癌侵袭和转移的关系

目的：探讨E—cadherin和MMP—2在胃癌组织中的表达与胃癌浸润转移的相关性。方法：采用S—P免疫组化染色，检测83例胃癌组织的E—cadherin和MMP—2的表达情况，20例胃良性病变手术病例作对照。结果：正常胃黏膜E—cadherin呈强阳性表达，胃癌组织中E—cadherin表达率明显减低，阳性表达率为16．9％(14／83)；E—cadherin表达减低与胃癌细胞分化程度、浸润深度、浸润型生长、淋巴结转移密切相关(P＜0．05)，而与TNM分期及肿瘤大小无关。MMP—2在正常胃黏膜中呈阴性表达，在胃癌组织中表达呈阳性，阳性率为78．3％(65／83)；MMP—2表达强度与胃癌分化程度、淋巴结转移、浸润深度、浸润型生长、TNM分期显著相关(P＜0．05)，而与肿瘤大小无关。E—cadherin与MMP—2的表达调控呈负相关，两者的表达水平呈负相关性。结论：E—cadherin的表达下调和MMP—2表达上调与胃癌浸润和转移密切相关，两者在癌组织中表达的检测有助于对胃癌患者预后的判断。     

肺鳞癌及淋巴结转移灶中CD44V6和E—钙粘素的表达及意义

目的：探讨CD44V6和E－钙粘素（E-cd)在肺鳞癌及淋巴结转移灶中的表达及其预后意义,方法应用免疫组织化学S－P法检测20例正常肺组织、72例肺鳞癌原发灶及淋巴结转移灶中CD44V6和E-cd表达,结果CD44V6在正常肺组织、肺鳞癌原发灶及淋巴结转移灶中阳性表达率分别为15．00％（3／20）、66．67％（48／72）和87．50％（63／72）。三者间有非常显著性差异（P＜0．01）。而E-cd的异常表达率分别为0（0／20）51．39％（37／72）和68．065（49／72）,三者间有非显著性差异（P＜0．01）。CD44V6阳性及E-cd异常表达率同肺鳞癌体积大小无关（P＞0．05）,与临床病理分期、癌分化程度及预后显著相关（P＜0．05）。结论CD44V6和E-cd可反映肺鳞癌的生物学特性,是预测其侵袭转移潜能和预后有价值的指标。     

胃癌原发灶与转移灶E-钙黏附素mRNA表达水平的比较研究

目的　评价E 钙黏附素 (E CD)mRNA在胃癌原发灶、淋巴结转移灶和腹腔液中的表达水平及其与胃癌生物学行为的关系。方法　采用逆转录聚合酶链反应 (RT PCR)对 35例进展期胃癌癌旁正常黏膜、原发癌组织、转移淋巴结和腹腔液中E CDmRNA水平进行检测 ,并与胃癌的生物学行为和腹膜转移相关因素进行比较。结果　全组癌旁正常黏膜、原发癌组织、转移淋巴结和腹腔液均检出E CDmRNA。与癌旁正常黏膜相比 ,胃癌原发组织E CDmRNA表达水平明显减弱 (P <0 .0 1) ,在浸润型、未分化型、弥漫状生长、侵透浆膜和Ⅲ、Ⅳ期胃癌中 ,其表达水平明显降低 (P <0 .0 5 )。随着淋巴结转移数目增加 ,胃癌原发灶中E CDmRNA表达水平也显著降低 (P <0 .0 5 ) ,但淋巴结转移灶中E CDmRNA表达明显增高 ,与其分化程度无关。转移淋巴结与相应原发灶的E CDmRNA表达指数差值在浸润型、未分化型、弥漫状生长、侵透浆膜、淋巴结转移严重及Ⅲ、Ⅳ期胃癌组织中明显增高 (P <0 .0 5 )。腹腔液中E CDmRNA表达指数在侵透浆膜、腱状及多彩型浆膜、ECC阳性者明显增高 (P <0 .0 1)。结论　胃癌原发灶的E CDmRNA表达水平降低 ,且表达水平与胃癌的恶性生物学行为呈正相关 ;胃癌转移淋巴结的E CDmRNA表达水平增高 ,并与胃癌的恶性生物学行为呈负相关。     

基质金属蛋白酶-7和E-钙黏附素在胃癌组织中的表达及其相关性

目的探讨基质金属蛋白酶．7（MMP．7）、E-钙黏附素（E—CD）在胃癌组织中的表达及其与胃癌侵袭、转移的相关性。方法采用原位杂交法,检测78例胃癌组织中MMP-7mRNA和E—CDmRNA的表达,观察二者与浸润深度和淋巴结转移之间的关系。结果胃癌组织中MMP-7mRNA和E-CDmRNA的阳性表达与浸润深度和淋巴结转移有关。MMP-7mRNA阳性表达的胃癌组织中E—CDmRNA的阳性表达率[9．09％（6／66）[低于MMP-7mRNA阴性表达的胃癌组织中E—CDmRNA的阳性表达率[66．70％（8／12）1,二者呈负相关（r=-0．269,P〈0．05）。结论MMP-7mRNA和E—CDmRNA的表达与胃癌的浸润、转移密切相关,且二者的表达呈负相关。检测MMP-7mRNA和E—CDmRNA在胃癌患者胃镜活检组织中的表达有助于预后判断。     

p53和c-myc异常表达与胃癌细胞多药耐药性的研究

目的：研究胃癌组织中p53和c-myc的表达与多药耐药性（MDR）的关系。方法：应用LSAB免疫组织化学方法研究67例胃癌标本中p53、c－myc和P-gp的表达。结果：胃癌中p53阳性32例（478％），c－myc阳性37例（55.2％），P－gp阳性39例（58．2％）。淋巴结转移阳性胃癌p53阳性率（56.9％）和c－myc阳性率（64．7％）显著高于淋巴结转移阴性的胃癌（P＜0．05）。p53的异常表达与mdr－1基因表达呈显著正相关（r=0．63，P＜005），而c－myc和mdr－1的表达无明显相关。结论：p53异常表达可增加mdr－l基因的表达，从而使胃癌细胞获得MDR表型。     

乳腺癌组织中E-cadherin和CD44V6及uPA的表达及意义

目的：探讨浸润性乳腺癌组织中细胞黏附分子E—cadherin、CD44V6和基质分解酶uPA的表达及意义。方法：SABC法检测86例乳腺癌和10例正常乳腺组织中E—cadherin、CD44V6与uPA的表达,探讨三者之间的相互关系。结果：E—cadherin在正常对照组均为强阳性表达,在乳腺癌组织中淋巴结转移组和无淋巴结转移组的阳性率分别为27．4％（17／62）和83．3％（20／24）,两组比较差异有统计学意义,X^2=22．067,P=0．000;CD44V6与uPA在正常对照组均呈阴性表达,在乳腺癌淋巴结转移组的阳性率分别为90．3％（56／62）和77．4％（48／62）;无淋巴结转移组的阳性率分别为62．5％（15／24）和16．7％（4／24）,两者的表达差异均有统计学意义（X^2=7．470、26．715,P=0．006、0．000）。相关分析结果显示,乳腺癌组织中E-cadherin的表达与CD44V6及uPA的表达均亦呈负相关。结论：E-cadherin和CD44V6及uPA的表达与乳腺癌的浸润转移密切相关,同步检测其在乳腺癌组织中的表达并综合分析三者之间的关系对评价乳腺癌细胞的侵袭转移能力及预后判断具有一定价值。     

层粘素ln及其受体ln-r在胆管癌淋巴结转移中的作用

目的：探讨人胆管癌细胞中LN和LN－R的表达水平与胆管癌转移的关系，方法：应用S－P免疫组化法对52例人胆管癌细胞中LN和LN－R的表达水平进行研究，结果：LN及LN－R高表达与胆管癌淋巴结转移呈明显相关，LN及LN－R阳性肿瘤淋巴结转移率（83％，55％），明显高于LN－R阴性肿瘤（15％，20％，P＜0．05），且LN及LN－R的表达与胆管癌组织学类型，分化程度亦存在明显相关（P＜0．05）。结论：LN及LN－R的表达在胆癌淋巴结转移中的关系起联合作用。     

胃癌术中腹腔冲洗液Cox-2 mRNA及CEA mRNA检测临床意义的探讨

目的：探讨腹腔冲洗液Cox-2 mRNA及CEA mRNA检测的可行性和临床意义。方法：前瞻性比较胃癌腹腔冲洗液RT-PCR法与常规细胞学法（PLC）检出脱落癌细胞的阳性率。结果：32例胃癌患者腹腔冲洗液中Cox-2 mRNA及CEA mRNA检出阳性率分别为53．1％（17／32）及56．3％（18／32），明显高于PLC检出癌细胞阳性率（21．9％），Х^2分别为5．497及4．433，P〈0．05。17例RT—PCR法检出阳性病例中，COX-2 mRNA法检出16例（94．1％），CEA mRNA法检出15例（88．2％），两种基因腹腔冲洗液脱落癌细胞检测阳性率大致相同，且检测阳性率与浆膜浸润阳性、浆膜浸润面积大、病理组织学类型、淋巴结转移和TNM病期呈正相关。结论：RT—PCR法检测胃癌腹腔冲洗液Cox-2 mRNA与CEA mRNA表达，可显著提高脱落癌细胞的检测阳性率，具有广泛的临床应用价值和意义。     

基质金属蛋白酶-2和组织蛋白酶D与胃癌生物学行为及腹膜转移的关系

目的:探讨基质金属蛋白酶-2(matrixmetalloproteinase-2,MMP-2)和组织蛋白酶D(cathepsinD,CD)在胃癌组织中的表达与胃癌生物学行为、腹膜转移的关系。方法:应用免疫组织化学方法检测55例胃癌MMP-2和CD表达情况。其中45例行腹腔脱落细胞学检查。结果:MMP-2和CD与浸润深度、胃浆膜分型、腹腔脱落癌细胞和临床分期密切相关(P<0.01);CD与淋巴结转移显著相关(P<0.01),MMP-2与淋巴结转移无明显关系,但淋巴结转移阳性者MMP-2表达率高于淋巴结转移阴性者。结论:MMP-2和CD高表达胃癌具有更强的侵袭、淋巴结转移能力及腹膜转移倾向。MMP-2和CD能较好的反映胃癌的恶性生物学行为,有助于判断预后。结转移显著相关(P<0.01),MMP-2与淋巴结转移无明显关系,但淋巴结转移阳性者MMP-2表达率高于淋巴结转移阴性者。结论:MMP-2和CD高表达胃癌具有更强的侵袭、淋巴结转移能力及腹膜转移倾向。MMP-2和CD能较好的反映胃癌的恶性生物学行为,有助于判断预后。     

Adhesion molecules and cancer metastasis

In accordance with the recent development of molecular biology and genetic technology for the study of adhesion molecule of cell-cell and cell-extracellular matrix interaction, correlation of these interactions with cancer metastasis have been progressing rapidly. For several years, active peptides derived from extracellular matrix (RGD) in fibronectin, YIGSR in laminin) have been used to inhibit tumor cell adhesion receptors, and block malignant cell adhesion and metastatic properties. Recently we have investigated the correlation between expression of cell-cell adhesion molecule (Ecadherin: E-CD) and metastasis in human esophageal, gastric and breast cancers by immunohistochemical staining using anti-human E-CD antibody (HE-CD-1). E-CD expression of these tumors was reduced in more than half cases when compared to normal epithelium. Moreover, E-CD expression of metastatic tumor in the primary sites was reduced significantly more than that of non-metastatic tumor. These results indicate that a firmly formed cluster of tumor cells might detach from the tumor nests with unstable adhesiveness, transit in the circulation and form metastatic foci in the secondary sites.     

胃癌组织中E—CD和UPA的表达及临床病理学评价

目的：探讨胃癌浸润、转移中细胞粘附分子ECD和基质分解酶UPA所发生的功能性改变及其与胃癌生物学行为的关系。方法：采用免疫组化SABC法对42例胃癌标本的ECD、UPA表达情况进行研究，分析了其与临床病理因素的关系及内在联系。结果：ECD在42例胃癌中阴性表达为66．7％（28例），UPA阳性率为64．3％（27例），ECD减低的表达，UPA的高表达与胃癌的高侵袭力、淋巴结转移、组织低分化和病理分期升高有关，且ECD（－）／UPA（＋）组较之ECD（＋）／UPA（－）组有明显的恶性生物学行为。结论：ECD表达减低和UPA的高表达均提示胃癌具恶性生物学行为，ECD／UPA共表达对胃癌生物学行为评估有重要意义。     

表皮-钙黏附素和Snail蛋白的表达与大肠癌侵袭转移及预后的关系

目的 研究表皮-钙黏附素(E-CD)和Snail蛋白在大肠癌组织中的表达及其与大肠癌侵袭、转移和预后之间的关系.方法 采用免疫组化EnVision法,检测E-CD和Snail蛋白在30例正常大肠黏膜、30例大肠腺瘤及142例大肠癌组织中的表达.结果 E-CD蛋白在正常大肠黏膜组织中的强阳性表达率为90.0%,明显高于其在大肠腺瘤和大肠癌组织中的强阳性表达率(63.3%和41.5%,P<0.05).Snail蛋白在大肠癌组织中的阳性表达率为52.1%,明显高于其在正常大肠黏膜和大肠腺瘤组织中的阳性表达率(6.7%和26.7%,P<0.05).E-CD蛋白的表达与大肠癌的分化程度、浸润深度、静脉侵犯、淋巴管侵犯、淋巴结转移以及Duke's分期有关(均P<0.05),而与患者的年龄、性别、肿瘤大小以及病理组织学类型无关(均P0.05).Snail蛋白的表达与大肠癌的分化程度、浸润深度、静脉侵犯、淋巴管侵犯、淋巴结转移、病理组织学类型以及Duke's分期有关(均P<0.05),而与患者的年龄、性别以及肿瘤大小无关(均P>0.05).E-CD蛋白与Snail蛋自在大肠癌组织中的表达呈负相关(r=-0.508).E-CD蛋白阳性表达者的术后1、3和5年生存率明显高于阴性表达者(P<0.05),Snail蛋白阴性表达者的术后1、3和5年生存率明显高于阳性表达者(P<0.05).淋巴结转移、Duke's分期、E-CD和Snail蛋白的表达可作为大肠癌独立的预后指标(均P<0.05).结论 E-CD和Snail蛋白的表达与大肠癌的侵袭、转移和预后明显相关,E-CD蛋白表达降低和Snail蛋白表达增强的大肠癌患者病期晚、预后差.     

Tumor‐associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer

Tumor lymphangiogenesis is a major prognostic indicator of gastric cancer. Tumor‐induced inflammation has been shown to attract tumor‐associated macrophages that affect lymphangiogenesis. However, detailed mechanisms of macrophage‐induced lymphangiogenesis have not been elucidated. Here, we evaluated the interaction between tumor‐associated macrophages and lymphatic endothelial cells (LECs) derived from lymph nodes (LNs) of human gastric cancer. Lymphatic endothelial cells were directly or indirectly cocultured with macrophages from healthy human blood, with or without the supernatant of the gastric cancer cell line, OCUM‐12. We analyzed the effect of cancer pretreated macrophages and of macrophages from metastatic LNs of gastric cancer on LECs. We observed morphological changes of LECs in coculture and assessed the gene expression of possible lymphangiogenic molecules of macrophages and LECs after contact coculture, and of cancer pretreated macrophages, by quantitative RT‐PCR. Specimens of metastatic LN of gastric cancer were immunofluorescently stained. We found that tubulogenesis of LECs was observed only in the contact coculture model. OCUM‐12 cells promoted macrophage‐induced tubulogenesis of LECs. Relative gene expression of MMP and adhesion molecules was significantly upregulated in both capillary‐forming LECs and cocultured macrophages. Cancer pretreated macrophages upregulated lymphangiogenic factors including inflammatory cytokines, MMPs, adhesion molecules, and vascular endothelial growth factor‐C. Blocking of intercellular adhesion molecule‐1 and macrophage activation suppressed tubulogenesis of LECs. Immunohistochemistry showed macrophages localized around lymphatic vessels. Our results suggested that interaction between LECs and macrophages may be an important initial step of tumor lymphangiogenesis developing LN metastasis. Understanding of its mechanisms could be useful for future therapeutics of gastric cancer.     

E-cadherin expression in renal cell cancer and its significance in metastasis and survival.

Decreased expression of E-cadherin (E-CD), a homotypic intercellular adhesion molecule, is considered to elicit detachment of tumour cells from primary lesions, which is the first stage of metastasis. Since renal cell cancer (RCC) shows a relatively high frequency of metastasis, we focused our interest on E-CD expression in RCC and its clinicopathological implications. We examined E-CD expression in normal kidney and RCC by immunohistochemical staining. In normal kidney, E-CD expression was localised in distal tubules and collecting ducts. In RCC, 20 of 106 primary lesions (18.9%) expressed E-CD, whereas none showed positive staining for eight metastatic lesions. There was a statistically significant correlation between loss of E-CD expression and advanced stages of RCC. Kaplan-Meier analysis showed better prognosis in the group with preserved E-CD expression than without E-CD expression (Cox-Mantel test, P = 0.022, the average follow-up was 32 months or until death). This study suggests that the patients with decreased E-CD expression may be associated with metastasis, resulting in poor prognosis. However, frequency of E-CD expression in RCC is lower than in other cancers, which may be derived from the localised distribution of E-CD expression in normal kidney.     

Re-expression of the cadherin-catenin complex in lymph nodes with metastasis in advanced gastric cancer: the relationship with patient survival

The cadherin-catenin complex has been recognized as an important factor associated with tumor metastasis. However, the clinical significance of the expression of adhesion molecules in lymph nodes with metastasis remains unclear. The aim of this study was to investigate the clinical significance of the re-expression of the cadherin-catenin complex in metastatic lymph nodes in patients with advanced gastric cancer. Immunohistochemical expression of E-cadherin, alpha- and beta-catenin were analyzed in 96 primary gastric cancers with serosal invasion and in 79 lymph nodes with metastasis. The expression levels of these adhesion molecules in primary tumors and lymph nodes with metastasis were compared. Ninety-four out of 96 primary tumors (98%) showed reduced expression of adhesion molecules. Out of 79 cases with lymph node metastasis, increased expression of one or more adhesion molecules in metastatic foci as compared with primary tumors was detected in 52 cases (66%). Re-expression of adhesion molecules in metastatic lymph nodes was detected in a more advanced stage. The overall 5-year survival rate of the 52 patients who had lymph nodes with metastasis with re-expression of adhesion molecules (8%) was significantly poorer than that of the 27 who had lymph nodes with metastasis without re-expression of adhesion molecules (33%, P = 0.0012). The re-expression of the cadherin-catenin complex in lymph nodes with metastasis may play an important role in the growth of cancer cells in metastatic foci. A comparison of the expression patterns of adhesion molecules between the primary tumor and metastatic lymph nodes may provide new prognostic information for patients with advanced gastric cancer.     

大肠癌组织上皮钙粘附素的表达及临床意义

目的：探讨人体大肠癌中上皮钙粘附素的表达是否与其转移潜能相关。方法：应用免疫组化方法检测44例大肠癌患者原发灶及临近非肿瘤大肠粘膜等不同组织中的上皮钙粘附素的表达情况。结果：正常大肠粘膜中上皮钙粘附素强烈表达，而其在原发灶中的染色特征发生改变，表达程度明显弱于临近非肿瘤大肠粘膜，且与大肠癌的生长方式、分化程度、淋巴道转移、Duke‘s分期等临床病理因素密切相关。结论：上皮钙粘附素的表达水平与大肠癌的浸润、转移明显相关。     

胃癌组织中maspin基因和HGF及E-cadherin的表达及相关性研究

目的:研究胃癌组织中maspin基因、HGF和E-cadherin的表达及相关关系。方法:应用免疫组化ABC法检测137例胃癌、66例不典型增生及54例正常胃黏膜组织中maspin基因、HGF和E-cadherin的表达。结果:在正常胃黏膜、不典型增生和胃癌组织中maspin基因表达分别为72·2%(39/54)、63·6%(42/66)和40·9%(56/137),差异有统计学意义,P<0·05;HGF表达分别是22·2%(12/54)、40·9%(27/66)和67·9%(93/137),差异有统计学意义,P<0·05;E-cadherin表达分别是88·9%(48/54)、77·3%(51/66)和52·5%(72/137),差异有统计学意义,P<0·05。maspin基因的表达与淋巴结转移、浸润深度及分化程度有关,与肿瘤大小、病理分型及TNM分期无关。HGF的表达与TNM分期、淋巴结转移相关,与病理分型、肿瘤大小、分化程度和浸润深度无关。E-cadherin表达与浸润深度、分化程度、淋巴结转移和TNM分期相关,与病理分型、肿瘤大小无关。Maspin基因表达与HGF呈负相关,r=-0·350,P<0·01;与E-cadherin呈正相关,r=0·433,P<0·01。结论:maspin基因在胃癌组织中表达下调可能导致细胞黏附减少及细胞的运动能力增加引起胃癌的发生发展和侵袭转移。     

细胞粘附分子CD44s表达与胃癌生物学行为关系的研究

目的：探讨细胞粘附分子ＣＤ４４ｓ在胃癌原发灶的表达与其生物学行为及淋巴结转移规律的关系,并进行临床病理学评价。方法：采用免疫组化方法（Ｓ－Ｐ法）观察了ＣＤ４４ｓ在７０例非癌胃组织和胃癌原发灶中的表达情况。对胃癌标本进行系统病理学检查。结果：ＣＤ４４ｓ在非癌胃组织中呈弱阳性表达,胃癌组织阳性表达率为４．３％。在淋巴结转移娄工大于５０％及转移至Ⅱ站以远,Ⅲ、Ⅳ期胃癌中ＣＤ４４ｓ表达增强,而与其它临床病