口腔鳞癌组织中KAI1 mRNA的表达

目的:探讨肿瘤转移抑制基因KAI1 mRNA在口腔鳞状细胞癌中的表达及其临床病理意义。方法:采用原位杂交法检测74例原发性口腔鳞癌(无淋巴结转移49例,有淋巴结转移25例)、21例相应的淋巴结转移灶、19例口腔黏膜白斑和10例正常口腔黏膜石蜡标本组织中KAI1 mRNA的表达情况。结果:KAI1 mRNA在正常黏膜组、黏膜白斑组、鳞癌无淋巴结转移组、有淋巴结转移组和淋巴结转移灶组中阳性表达率分别为100%、84.2%、61.2%、28.0%和4.8%,其中无淋巴结转移鳞癌组显著低于正常和黏膜白斑组,P<0.05,淋巴结转移组显著低于无淋巴结转移组,P=0.045,淋巴结转移灶组显著低于相应鳞癌组,P=0.040。低分化鳞癌的KAI1阳性表达率显著低于高、中分化鳞癌,P<0.001。KAI1的表达与鳞癌患者的年龄、性别、肿瘤大小和浸润深度以及pT-MN分期无显著相关,P>0.05。结论:KAI1 mRNA表达下调可能与口腔鳞状细胞癌的组织分化程度和淋巴结转移有关。     

Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma

BACKGROUND: KAI1/CD82, a tumor metastasis suppressor gene, is correlated inversely with the progression and invasion of several tumors. It also has been reported that the KAI1 gene is related to the tumor suppressor gene p53. This study was performed to clarify the correlation between KAI1/CD82 expression and clinicopathologic characteristics and p53 expression in patients with esophageal squamous cell carcinoma (ESCC). The authors also investigated mutation of the KAI1 gene coding region to determine whether this may reduce KAI1 expression in ESCC. METHODS: Using immunohistochemistry with anti-KAI1 polyclonal antibody and monoclonal antibody against p53, KAI1/CD82 and p53 expression were detected in 55 patients with ESCC who had undergone surgery. The authors examined the KAI1 gene mutation in 22 patients with ESCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. RESULTS: KAI1/CD82 expression was positive in 36 of 55 patients (65.5%). There was a significant inverse correlation between KAI1/CD82 expression and regional lymph node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046). The survival rates of KAI1/CD82 negative patients were poorer than those of positive patients (P = 0. 024). The correlation between KAI1 positive and p53 positive tumors was not statistically significant. None of the 22 patients with ESCC showed mutation of the KAI1 gene by PCR-SSCP. In one patient, there was polymorphism in the SSCP assay and DNA sequencing. CONCLUSIONS: The authors demonstrated immunohistochemically that the expression of KAI1 protein appeared to be correlated with lymph node metastasis. Mutation does not seem to be a mechanism for dysregulation of the KAI1 protein in ESCC.     

Motility-related protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma

Although the mechanisms of action of the transmembrane superfamilies, motility-related protein-1 (MRP-1/CD9) and KAI1/CD82, are not well known, they are reported to suppress the metastasis of several kinds of cancers. The suppression of cell motility by MRP-1/CD9 may cause suppression of the metastasis. As we could not find any reports concerning the expression of MRP-1/CD9 and KAI1/CD82 in oesophageal cancers we investigated their expression in oesophageal specimens. We conducted immunohistochemical staining for MRP1/CD9 against 108 cases of oesophageal squamous cell carcinoma using anti-MRP-1/CD9 monoclonal antibody M31-15, and for KAI1/CD82 against 104 cases using anti-KAI1/CD82 monoclonal antibody C33. To investigate the gradual expression of MRP-1/CD9 and KAI1/CD82, 24 oesophageal dysplasias were immunohistochemically stained using the same method and then investigated. The expression of both MRP-1/CD9 and KAI1/CD82 were positive on the cell membranes of normal oesophageal epithelial cells, but reduced or negative in the cancer cells. Reduced MRP-1/CD9 expressions significantly correlated to tumour depth (P = 0.0009). We found a significantly greater number of reduced or negative expression of MRP-1/CD9 and KAI1/CD82 in lymph node metastatic cases (P = 0.0003 and P= 0.0129, respectively), but not in distant metastatic cases. The 5-year survival rate of MRP-1/CD9-negative and reduced patients was significantly worse than those of positive patients (n = 108, curative cases, RO). Few cases remained KAI1/CD82-positive (9.6%; 10/104) in oesophageal cancer. Twenty (83.3%) and twenty-two (91.7%) cases out of 24 dysplasias were defined as KAI1/CD82-positive and MRP1/CD9-positive, respectively. The decrease in MRP-1/CD9 and KAI1/CD82 expression may facilitate lymph node metastasis in oesophageal squamous cell carcinomas. Knowing the status of the expression of MRP-1/CD9 appears helpful in predicting the prognosis for each patient.     

KAI1/CD82蛋白在宫颈鳞状细胞癌的表达及临床意义

目的:探讨KAI1/CD82蛋白在宫颈鳞状细胞癌(CSC)中的表达及与临床参数的关系.方法: 应用免疫组化SP法,检测52例宫颈鳞癌组织中KAI1/CD82蛋白表达水平.结果: 有淋巴结转移宫颈癌组织和无淋巴结转移宫颈癌组织中KAI1/CD82蛋白表达率分别为25%(3/12)、62.5%(25/40),两者比较有显著性差异(P＜0.05),KAI1/CD82的表达与宫颈癌的分级、浸润深度及临床分期有关.结论: KAI1/CD82蛋白表达可作为预测宫颈癌预后的一个有用指标.     

KAI1/CD82在原发性乳腺癌中的表达及其临床意义

目的:探讨KAI1/CD82在乳腺癌中的表达及其临床意义。方法:采用RT-PCR和免疫组化方法对69例原发性乳腺癌组织、癌旁组织和区域淋巴结组织中KAI1 mRNA和CD82蛋白的表达进行研究。结果:在69例原发性乳腺癌中,癌旁组织中KAI1基因在区域淋巴结转移阴性组和区域淋巴结转移阳性组的mRNA表达无显著性差异(P>0.05)。癌组织和区域淋巴结组织中KAI1基因在区域淋巴结转移阴性组和区域淋巴结转移阳性组的mRNA表达有显著差异(P<0.05)。CD82表达与临床病理类型以及PR表达无相关性(P>0.05),而与临床分期、组织学分级、区域淋巴结转移、远处转移、ER表达有相关性(P<0.05)。结论:KAI1/CD82的表达与乳腺癌的转移及某些临床病理因素有关,具有一定的临床指导意义。     

KAI1/CD82在宫颈鳞癌组织中的表达及其与淋巴结转移的关系

目的:探讨KAI1/CD82蛋白在宫颈鳞癌中的表达及其与宫颈癌淋巴结转移的关系。方法:采用免疫组化S-P法检测KAI1/CD82在10例正常宫颈组织、15例不典型增生宫颈组织及64例宫颈鳞癌组织中的表达,分析表达结果与临床病理特征的关系。结果:从正常宫颈组织到宫颈不典型增生组织再到宫颈癌组织,KAI1/CD82阳性表达率呈递减趋势。KAI1/CD82的表达与宫颈癌病理分级、宫颈癌淋巴结转移明显相关而与临床分期、浸润深度、病理类型、癌灶大小、患者年龄等无关。结论:宫颈鳞癌中KAI1/CD82表达下调与淋巴结转移显著相关,可用来预测淋巴结的转移状况。     

PLCE1在口腔鳞状细胞癌中的表达及其临床意义

目的:探讨磷脂酶Cε1（phospholipase C epsilon－1,PLCE1)在口腔鳞状细胞癌(OSCC)组织中的表达及其与临床病理特征和患者预后的关系。方法:应用免疫组织化学方法检测PLCE1在83例OSCC组织和20例正常口腔黏膜组织中的表达,并分析 PLCE1表达与OSCC临床病理特征的关系;采用Kaplan-Meier法进行生存分析,Cox 风险比例回归模型分析影响OSCC患者预后的独立因素。结果:PLCE1在OSCC组织与口腔正常黏膜组织中高表达率分别为53.01%和15.00%,差异有统计学意义（P=0.002）。PLCE1的表达与患者年龄、性别、吸烟无相关性,而与肿瘤分化程度、T分期、临床分期、N分期有密切关系。单变量分析显示临床分期、PLCE1、T分期、N分期是影响OSCC预后的因素,双变量分析显示PLCE1是其独立预后因素。结论:PLCE1过表达与OSCC的发生、发展密切相关,可作为判断OSCC恶性程度和不良预后的参考指标。     

KAI1 / CD82 和 MMP - 7 在多原发结直肠癌中的表达及临床意义简

目的：探讨KAI1／CD82和MMP-7的表达与多原发结直肠癌浸润、转移的关系。方法：应用免疫组织化学法检测KAI1／CD82和MMP-7在27例多原发结直肠癌及36例单发结直肠癌组织中的表达。结果：多原发结直肠癌组KAI1／CD82阳性表达率为76．7％,单发结直肠癌组KAI1／CD82阳性表达率为50．0％,两组有显著性差异（P〈0．05）。多原发结直肠癌组MMP-7阳性表达率为60．5％,单发结直肠癌组MMP-7阳性表达率为83．3％,两组有显著性差异（P〈0．05）。多原发结直肠癌组和单发结直肠癌组KAI1／CD82、MMP-7的阳性表达率在TNM分期、分化程度、浸润深度和有无淋巴结转移方面差异均有显著性意义。结论：KAI1／CD82、MMP-7的表达与结直肠癌的分期、分化程度、浸润深度和淋巴结转移有关。多原发结直肠癌的浸润、转移与KAI1／CD82和MMP-7的异常表达有关,它们可能协同作用,抑制肿瘤的侵袭和转移能力而促进多原发结直肠癌的发生。     

KAI1/CD82在神经母细胞瘤组织中的表达及其与预后的关系

背景与目的KAI1/CD82是近年来发现的肿瘤转移抑制基因,它的失活与某些肿瘤的进展和浸润有关。本研究旨在通过检测KAI1/CD82蛋白在神经母细胞瘤中的表达,探讨其与神经母细胞瘤临床病理特征和预后的关系。方法用免疫组化EnVision法检测90例神经母细胞瘤瘤组织中KAI1/CD82蛋白的表达,结合临床资料与随访资料进行统计学分析。结果39.3%(11/28)节细胞神经母细胞瘤KAI1/CD82呈阳性表达,14.5%(9/62)神经母细胞瘤KAI1/CD82呈阳性表达(P=0.014)。KAI1/CD82的表达与神经母细胞瘤的分化程度呈显著性正相关,且KAI1/CD82的表达与临床分期呈显著性负相关(P=0.003)。结论KAI1/CD82表达的改变是神经母细胞瘤发生的早期事件,其表达下调是神经母细胞瘤分化和转移的一个潜在标志。此标记物可能作为临床评估预后的综合指标之一。     

Expression of KITENIN, a KAI1/CD82 binding protein and metastasis enhancer, in bladder cancer cell lines: relationship to KAI1/CD82 levels and invasive behaviour

KITENIN is a newly identified binding partner of the KAI1/CD82 metastasis suppressor. Recent studies using a mouse model of colon cancer, have suggested that KITENIN might be a metastasis enhancer whose functions are modulated by an interaction with KAI1/CD82. To begin exploration of the possible importance of KITENIN to human cancer, we examined KITENIN mRNA (by RT-PCR) and protein expression (by Western blotting) in a large series of bladder cancer cell lines, and then compared these levels to the expression of KAI1/CD82 and of previously determined in vitro invasive behaviour of these same cancer cell lines. We report that KITENIN was uniformly expressed in all cancer cell lines, but those lines in which KAI1/CD82 was not detected, had a higher in vitro invasive ability and altered actin organisation (as determined by fluorescence microscopy), than those lines in which KAI1/CD82 was present. Our data suggest that the relationship between KITENIN and KAI1/CD82 may be an important determinant of tumour cell behaviour.     

KAI1/CD82和E-cadherin在子宫内膜癌的表达

[目的]研究KAI1/CD82与E-cadherin在子宫内膜癌组织中的表达及其与临床病理参数的关系。[方法]采用免疫组织化学EnVision二步法检测76例子宫内膜癌,15例非典型增生子宫内膜和20例正常增生期子宫内膜组织中KAI1/CD82、E-cadherin的表达。[结果]KAI1/CD82在正常增生期子宫内膜、非典型增生内膜、子宫内膜癌的阳性表达率分别为95%、93.3%和60.5%;E-cadherin在正常增生期子宫内膜、非典型增生内膜、子宫内膜癌的异常表达率分别为0、6.67%和55.26%。KAI1/CD82在子宫内膜癌的表达与组织学分级、肌层浸润程度呈负相关(P=0.000,P=0.01)。E-cadherin在子宫内膜癌的表达与组织学分级及组织学类型有关。KAI1/CD82与E-cadherin在子宫内膜癌中的表达呈显著性相关(P<0.01)。[结论]KAI1/CD82表达下调和E-cadherin异常表达增高与子宫内膜癌的进展有关。     

子宫颈鳞癌组织中运动相关蛋白的表达

 【摘要】　目的　探讨子宫颈鳞癌组织和正常子宫颈组织中运动相关蛋白（MRP1／CD9）的表达及其临床意义。方法　应用免疫组化SABC法，检测13份正常子宫颈上皮和53份子宫颈癌组织中MRP1／CD9的表达，并进行比较分析。结果　13例正常子宫颈上皮中MRP1／CD9的表达均为阳性，53份子宫颈癌组织中33份MRP1／CD9的表达降低（P＜0.05），子宫颈癌组织MRP1／CD9的表达与淋巴结转移显著相关（P＜0.05）。结论　MRP1／CD9在子宫颈鳞癌中表达下调，与子宫颈癌淋巴结转移有关。     

肿瘤转移抑制基因KiSS-1在胰腺癌组织中的表达及意义

目的:检测KiSS-1mRNA及KiSS-1蛋白metastin在胰腺癌组织中的表达,探讨其在胰腺癌浸润及转移中的作用.方法:采用逆转录多聚酶链反应(RT-PCR)法及免疫组织化学S-P法检测42例胰腺癌,10例慢性胰腺炎及12例正常胰腺组织中KiSS-1mRNA及KiSS-1蛋白metastin的表达情况及与各种临床病理参数的关系.结果:KiSS-1mRNA及Kiss-1蛋白metastin在胰腺癌组中的阳性表达显著低于慢性胰腺炎组及正常胰腺组(P＜0.01);KISS-1mRNA和KiSS-1蛋白metastin的表达均与胰腺癌临床分期及淋巴结转移有关(P＜0.05);二者在胰腺癌组织中的表达存在明显相关性.结论:肿瘤转移抑制基因KiSS-1在抑制胰腺癌的浸润和转移过程中可能起着重要的作用.     

喉鳞癌组织Cyclin G1基因表达及其临床意义的研究

目的：探讨Cyclin G1基因在喉鳞状细胞癌组织中的表达及其临床意义。方法：取40例喉鳞癌组织、10例癌旁正常喉黏膜组织及10例声带息肉组织，应用RT-PCR方法检测Cyclin G1基因mRNA的表达，并分析表达结果与患者临床病理特征之间的关系。结果：喉癌组织中的Cyclin G1 mRNA表达明显高于癌旁正常黏膜组织及声带息肉组织中的表达，P〈0．05。中、低分化与高分化喉癌比较，后者Cyclin G1表达较低，差异有统计学意义，P〈0．05。有淋巴结转移组比无淋巴结转移组喉癌组织Cyclin G1表达显著增高，P〈0．05。Cyclin G1的表达与癌组织分化及颈淋巴结转移有关。结论：Cyclin G1在喉癌组织中有异常高表达，并与喉癌发生发展有一定联系，其高表达可能是喉癌预后不良的因素之一。     

Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in primary oral squamous cell carcinoma and corresponding metastases in cervical lymph nodes: association with the metastasis suppressor CD82

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are 5-fluorouracil (5-FU) metabolizing enzymes and are involved in the sensitivity of carcinoma patients to 5-FU. Although 5-FU is often used for the treatment of oral carcinoma, there has not been any investigation into the expression of these enzymes in metastatic lymph nodes or of their roles in the effectiveness of 5-FU in treating lymph node-metastatic cancer. Oral squamous cell carcinoma (OSCC) often metastasizes to the lymph nodes, and these enzymes may be significant in the survival of patients with this disease. This study investigated the expression of TS and DPD in cervical lymph node metastases and its relationship with primary OSCC, as well as the interaction between these enzymes and Kangai 1(KAI1/CD82) which is a metastasis suppressor protein. Surgical specimens from 20 cases of OSCC with lymph node metastasis, 20 cases of OSCC without lymph node metastasis, and 10 cases of normal mucosa were examined by immunohistochemistry. The relationship between TS and DPD expression and clinicopathological data was analyzed. TS and DPD proteins were overexpressed in primary OSCC compared to that in normal mucosa. TS expression of the primary oral cancer cells in the group with lymph node metastasis was higher than that of those without. DPD expression did not significantly correlate with the occurrence of lymph node metastasis, nor was it different between primary oral cancer cells and cervical metastases. CD82 expression was significantly reduced in lymph node metastases. These findings indicate that TS and CD82 may be of great value in assessing lymph node metastasis of OSCC, and could be taken as new targets for therapy of metastatic OSCC.     

KAI1基因对人鼻咽癌细胞株HNE-1增殖、侵袭及转移能力的影响

目的:研究转移抑制基因KAI1对人鼻咽癌细胞体外增殖、侵袭及转移能力等生物学效应的影响.方法:通过腺病毒载体将KAI1基因转染人鼻咽癌细胞株HNE-1, RT-PCR法检测转染效果; MTT法检测鼻咽癌细胞转染KAI1基因后体外增殖能力的变化;FCM法检测细胞生长周期分布; Transwell侵袭小室检测细胞侵袭能力的改变;细胞同质黏附实验检测细胞黏附力的变化.结果:当腺病毒载体 rAd-KAI1效价为 30 MOI时,对HNE-1细胞的转染率可达92%;转染48 和72 h 时,rAd- KAI1转染组细胞的增殖明显受到抑制,抑制率分别为17%和30%;G0/G1期细胞数量较对照组增多,S期细胞数量减少;转染组的穿膜细胞数为(52.5±4.2)个,明显低于对照组的(167.4±3.5)个,差异有统计学意义(P<0.05);转染组的细胞同质黏附作用高于对照组(P<0.05).结论:腺病毒载体成功介导了抑癌基因KAI1转染进入鼻咽癌HNE-1细胞,并取得较高的转染率.KAI1基因可能通过阻滞HNE-1细胞生长周期,从而抑制细胞增殖.KAI1基因能够抑制HNE-1细胞侵袭能力,其机制可能为KAI1基因增强了鼻咽癌细胞的黏附力所致.     

胃腺癌组织中KAI1/CD82蛋白的表达及其意义

目的 探讨KAI1／CD82蛋白在胃腺癌组织中表达及其与胃癌生物学行为的关系。方法应用免疫组织化学技术S-P法检测68例胃腺癌组织中KAI1／CD82蛋白的表达，以20例非肿瘤性胃黏膜组织作对照。对随访14个月～13年的35例做生存分析。结果 68例胃腺癌组织KAI1／CD82蛋白阳性表达率为26、5％（18／68），对照组胃黏膜组织阳性表达率95．0％（19／20）；高／中分化胃腺癌KAI1／CD82蛋白阳性表达率较低分化者为高，分别为41．4％（12／29）、15．4％（6／39），P〈0．05；无淋巴结转移胃腺癌的KAI1／CD82蛋白阳性表达率较有淋巴结转移者为高，分别为45.5％（10／22）、5.3％（8／46），P〈0.05；侵及黏膜及黏膜下层、肌层和浆膜层胃腺癌KAI1／CD82蛋白阳性表达率分别为66、7％（4／6）、34.8％（8／23）、15.4％（6／39），P〈0.05。KAI1／CD82蛋白在Ⅰ～Ⅱ期胃腺癌阳性表达率为37.0％（17／46），在Ⅲ～Ⅳ期胃腺癌中阳性表达率为13.6％（1／22），P〈0.05。KAI1／CD82蛋白阳性患者术后1、3、5、7、10年生存率分别为100.0％（7／7）、85.7％（6／7）、57.1％（4／7）、42.9％（3／7）和28．6％（2／7），而KAI1／CD82阴性患者术后生存率分别为89、3％（25／28）、42、9％（12／28）、14．3％（14／28）、7．1％（2／28）和3、6％（1／28）。KAI1／CD82蛋白阳性患者术后1、3、5、7和10年生存率比KAI1／CD82阴性患者术后1、3、5、7和10年生存率显著提高，P〈0．05。结论 KAI1／CD82蛋白在胃腺癌的表达与肿瘤浸润深度、分化程度、临床分期及淋巴结转移有关，与患者性别、年龄无关。检测KAI1／CD82蛋白有助于临床评估病情，判断预后。     

KAI1/CD82的表达与大肠腺癌的相关性分析

目的　初探KAI1/CD82在大肠腺癌组织中的表达。方法　采用免疫组织化学方法 (S -P法 ) ,对 2 41例大肠腺癌组织中KAI1/CD82的表达水平进行半定量研究 ,并探讨其与 2 41例大肠腺癌病理学分级及转移、浸润的相关性。结果　大肠腺癌组织中KAI1/CD82的表达与病理学分级、浸润深度、淋巴结及血道转移呈负相关 (P <0 0 1)。结论　大肠腺癌组织中KAI1/CD82的表达可作为评估肿瘤细胞的转移潜能的一个指标。     

KAI1/CD82与恶性肿瘤

KAI1/CD82属TM4SF的成员,其结构为细胞膜糖蛋白,有4个高度保守的穿膜结构区.最近的研究表明,KAI1蛋白对多种肿瘤的转移具有抑制作用.有转移潜能的肿瘤细胞或已发生转移的肿瘤组织内KAI1表达下调或不表达.KAI1可作为判断肿瘤预后的一个指标,并将为肿瘤的治疗提供一个新的途径.