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.     

肺癌组织中KAI 1/CD82和整合素α5的表达及意义

目的:研究KAI 1/CD82和整合素α5在肺癌组织中的表达及其与临床病理特征的关系.方法:应用免疫组织化学方法检测110例肺癌组织中KAI 1/CD82及整合素α5的表达情况.结果:KAI 1/CD82在肺癌中的表达阳性率为37.3%,α5的表达阳性率为44.5%.二者的表达水平在淋巴结转移方面差异有显著性意义(r＞0,P＜0.05).KAI 1/CD82的表达在TNM分期方面差异亦呈显著性意义(r＞0,P＜0.05).二者的表达水平与年龄、性别、病变部位、肿瘤大小、分化程度及病理类型无关(P＞0.05).结论:KAI 1/CD82和整合素α5与淋巴结转移相关,二者可作为判定肺癌浸润和转移的指标.     

KAI1/CD82、Integrin α5在乳腺癌中的表达及其临床意义

目的:探讨KAI1/CD82和Integrin α5在乳腺癌中的表达及其临床意义。方法:用免疫组织化学SP法检测64例乳腺癌组织KAI1/CD82和Integrin α5的表达。结果:乳腺癌组织中KAI1/CD82和Integrin α5阳性表达与正常乳腺组织比较有显著差异(P<0.05);两种基因蛋白表达与肿瘤临床分期及淋巴结转移密切相关,差异有统计学意义(P<0.05);二者在乳腺癌组织中呈正相关(P<0.01)。结论:KAI1/CD82和Inte-grin α5蛋白的表达与乳腺癌的演进和转移密切相关,检测其表达异常对判断临床进展以及推测预后有一定的参考价值。     

KAI1/CD82的表达与乳腺癌转移、预后的关系

目的探讨KAI1/CD82在乳腺癌进展中的作用及其在预后判断中的价值。方法采用免疫组化方法对60例有临床和随访资料的乳腺癌组织进行KAI1/CD82蛋白表达的研究。以15例良性乳腺瘤,15例正常乳腺组织作对照,分析与临床病理指标的关系。结果在乳腺癌原发灶中KAI1/CD82阳性表达41．66%,较正常乳腺组织（80%）、良性乳腺瘤（73．33%）明显减少（P＜0．01、P＜0．05）。KAI1/CD82在有淋巴结转移、周围组织侵润、远处脏器转移肿瘤中表达显著降低（P＜0．01、P＜0．05、P＜0．05）,生存5年以上者的KAI1/CD82蛋白阳性表达率59．38%,明显高于生存时间不超过5年者21．43%（P＜0．01）。患者的术后复发情况与KAI1/CD82表达无关。结论KAI1/CD82的异常表达可能参与了乳腺癌的恶性进展。检测KAI1/CD82的表达对判断肿瘤的侵袭、转移及乳腺癌患者预后有一定的参考价值。     

检测KAI1/CD82蛋白在结肠腺癌中表达的临床意义

目的　KAI1是一种特异性抑制肿瘤转移的基因 ,其蛋白产物为KAI1/CD82。通过检测 6 4例结肠腺癌石蜡切片的KAI1/CD82蛋白表达 ,探讨其与预后等临床因素的相关性。方法　肿瘤经福尔马林固定 ,石蜡包埋。免疫组化方法检测石蜡切片中KAI1/CD82蛋白表达水平。生物学统计采用 χ2 检验法。生存曲线采用Kaplan Meier软件绘制。结果　KAI1/CD82蛋白呈现棕褐色、细颗粒状物 ,弥漫性分布结肠腺癌细胞膜上。KAI1/CD82蛋白在结肠腺癌组织中表达阳性率为 5 1.5 6 %。生物学统计结果表明 ,KAI1/CD82蛋白表达与淋巴结转移、远处转移及肿瘤临床分期等密切相关 ,有统计学意义 ;而与肿瘤患者的年龄和性别、肿瘤大小、分化程度及肿瘤部位等无关。KAI1/CD82蛋白阳性结肠腺癌患者的术后生存期明显高于阴性患者 ,前者平均术后生存期为 5 4 .2 7± 2 1.5 1月 ,而后者仅为 37.5 5± 15 .17月 ,具有统计学意义。结论　KAI1/CD82表达水平与结肠腺癌分期、淋巴结转移及远处转移关系密切 ,可能和其它指标一起作为判断结肠腺癌预后的指标之一 ,对术后进一步治疗具有一定的指导意义。     

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。     

非小细胞肺癌中KAI1基因表达及其与P53的相关性研究

背景与目的近年研究表明,KAI1表达下调与多种肿瘤的转移有关,但其与非小细胞肺癌的关系研究较少,且导致其下调的机制尚未明确。本研究从mRNA和蛋白水平探讨KAI1基因在非小细胞肺癌组织中的表达与患者临床病理特征的关系及其与突变型P53蛋白表达的关系。方法采用RTPCR和Westernblot法,检测48例肺癌患者手术切除的新鲜癌组织标本中KAI1mRNA、KAI1/CD82及突变型P53蛋白的表达,20例肺部良性疾病组织和正常肺组织作为对照。结果肺癌组和对照组中KAI1mRNA的阳性率分别为52%和90%(P<0.01),KAI1/CD82蛋白的阳性率分别为48%和85%(P<0.01),突变型P53蛋白阳性率分别为65%和5%(P<0.01)。KAI1mRNA、KAI1/CD82和突变型P53蛋白阳性率与肺癌患者临床分期、细胞分化程度和淋巴结转移有密切关系(P<0.05或P<0.01)。肺癌组织中KAI1mRNA与KAI1/CD82表达呈密切相关性(P<0.01),KAI1/CD82与突变型P53蛋白的表达亦呈显著相关性(P<0.05),KAI1mRNA与突变型P53表达无明显相关性(P>0.05)。结论KAI1基因的低表达可能与非小细胞肺癌的发生、发展和转移有关;其下调的机制可能主要发生在转录水平并与p53基因有关,二者可能作为评估肺癌患者转移潜能的指标。     

KAI1基因在非小细胞肺癌中的表达及意义

 目的 探讨肿瘤转移抑制基因KAI1基因在非小细胞肺癌组织中的表达及其与患者临床病理指标的关系。 方法 采用RT-PCR和Western blot法,检测48例肺癌患者手术切除的新鲜肺癌组织标本和20例同期手术切除的肺部良性病变周围正常组织中KAI1 mRNA、KAI1/CD82,并结合患者的临床病理资料对其结果进行统计分析。 结果 肺癌组织和肺部良性病变组织中KAI1 mRNA的阳性率分别为52%和90%,KAI1/CD82蛋白的阳性率分别为48%和85%,肺癌组KAI1mRNA及KAI1/CD82蛋白表达均低于肺部良性病变组（P<0.01）;KAI1mRNA、KAI1/CD82表达水平与肺癌患者的临床分期、组织分化程度、淋巴结转移有关（P<0.05）,其中KAI1/CD82表达与淋巴结转移状况密切相关(P<0.01),肺癌组织中KAI1 mRNA与KAI1/CD82表达有相关性（P<0.01）。 结论 KAI1基因的低表达可能与非小细胞肺癌的发生、发展和转移有关;其下调的机制可能主要发生在转录水平;KAI1基因的表达可作为一项评估肺癌患者转移潜能的指标。     

KAI1／CD82 mRNA和蛋白在鼻咽癌组织中的表达及意义

目的 探讨KAI1／CD82 mRNA和CD82蛋白在鼻咽癌组织中的表达及其与临床病理特征的关系。方法 采用免疫组化SP法检测70例鼻咽癌和30例正常鼻咽部组织中KAI1／CD82蛋白的表达情况;逆转录聚合酶链式反应（RT-PCR）检测28例鼻咽癌和15例正常鼻咽部新鲜组织中KAI1／CD82 mRNA的表达情况。分析KAI1／CD82 mRNA和CD82蛋白的表达与临床病理特征之间的关系。结果 KAI1／CD82 mRNA在鼻咽癌组织中的阳性表达率为42.9％（12／28）,低于正常鼻咽部组织中的73.3％（11／15）,差异无统计学意义（P＞0.05）;KAI1／CD82蛋白在鼻咽癌组织中的阳性表达率为44.3％（31／70）,低于正常鼻咽部组织中的700％（21／30）,差异有统计学意义（P＜0.05）。KAI1／CD82 mRNA和CD82蛋白在鼻咽癌组织中的表达与患者的性别、年龄、病理类型、T分期均无关（P＞0.05）,而与淋巴结转移有关。KAI1／CD82 mRNA和CD82蛋白在无淋巴结转移组中的阳性表达率分别为85.7％和68.4％,明显高于淋巴结转移组的28.6％和35.3％,差异均有统计学意义（P＜0.05）。KAI1／CD82 mRNA和CD82蛋白在N1、N2、N3亚组间表达率的差异无统计学意义（P＞0.05）。结论 KAI1／CD82 mRNA和CD82蛋白在鼻咽癌组织中表达下调,该基因可以抑制鼻咽癌发生、发展及淋巴结转移,有望作为鼻咽癌诊断和预后判定的一种有效分子标记物。     

Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model

Conventional therapies still remain less effective for metastasis of lung cancer, thus leading to a poor prognosis for this disorder. Although the processes involved in metastasis have not yet been clearly elucidated, our previous studies have shown that higher expression levels of MRP-1/CD9 and KAI1/CD82 in cancer cells are significantly correlated with less metastatic potency. To determine whether the gene transfer of these tetraspanins into lung tumor cells may be a useful strategy to regulate metastasis, we adopted an orthotopic lung cancer model produced by the intrapulmonary implantation of Lewis lung carcinoma (LLC) cells and evaluated the metastatic growth in the mediastinal lymph nodes using two different methods of gene delivery as follows: (a) the implantation of LLC cells preinfected with adenovirus encoding either MRP-1/CD9 cDNA, KAI1/CD82 cDNA, or LacZ gene into the mouse lung and (b) the intratracheal administration of these adenoviruses into the mice orthotopically preimplanted with LLC cells. In both cases, we found that the delivery of either MRP-1/CD9 or KAI1/CD82 cDNA dramatically reduced the metastases to the mediastinal lymph nodes in comparison with those of LacZ gene delivery, without affecting the primary tumor growth at the implanted site. These results reemphasize the important role of MRP-1/CD9 and KAI1/CD82 in the suppression of the metastatic process and also show the feasibility of gene therapy when using these tetraspanins for lung cancer to prevent metastasis to the regional lymph nodes. This strategy may therefore be clinically applicable as a prophylactic treatment to suppress the occurrence of lymph node metastasis.     

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.     

MRP-1/CD9 and KAI1/CD82 expression in normal and various cancer tissues

As part of our evaluation of MRP-1/CD9 and KAI1/CD82 as prognostic predictors among patients with cancer, we have extended our studies to solid tumors of a variety of anatomical sites. Normal tissues were included for comparison. Immunohistochemical techniques were used throughout. Our results indicate that MRP-1/CD9 was strongly expressed by many normal tissues, including the epithelium of the gastrointestinal tract, alveolar epithelium of the lung, urothelium and smooth muscle. Expression was weak in the pituitary gland, spleen and hepatocytes, and absent in testes and spinal cord. KAI1/CD82 was also expressed by many normal tissues, but was absent in some MRP-1/CD9-positive tissues (e.g., smooth muscle, adrenal cortex, urothelium, myelin of peripheral nerves, epithelium of amnion). On the other hand, KAI1/CD82 was strongly expressed in spinal cord gray matter, which was MRP-1/CD9-negative. Expression of these glycoproteins was detected in almost all types of tumors examined. In certain cancers, MRP-1/CD9 and KAI1/CD82 positivity was inversely related to lymph node involvement. Whereas lymph node metastases were present in 22.2% of lung cancer patients whose tumors were MRP-1/CD9 and KAI1/CD82-positive, 65.5% of patients with MRP-1/CD9 and KAI1/CD82-reduced/negative tumors had lymph node metastases. A similar inverse relationship was seen in colon cancer and breast cancer patients with respect to MRP-1/CD9 expression. The present data, together with our previous results suggest that evaluating the MRP1/CD9 and KAI1/CD82 status of cancers of the lung, breast and colon may provide useful information on the metastatic potential of the tumors.     

KAI1/CD82 expression as a prognosic factor in sporadic colorectal cancer

BACKGROUND: Since its identification as a suppressor gene for prostate cancer metastasis, down-regulation of KAI1/CD82 in a variety of malignancies has been reported. MATERIALS AND METHODS: Using immunohistochemistry, we examined KAI1/CD82 expression in surgical specimens obtained from 70 patients with advanced colorectal cancer and its correlation with clinicopathological factors, to clarify their prognostic significance. RESULTS: KAI1/CD82 expression was positive in 55% of the 70 colorectal cancers. There were statistically significant correlations between KAI1/CD82 expression and Dukes' stage, venous invasion, lymph node metastasis, tumor differentiation and liver metastasis. The significant correlation between KAI1/CD82 expression and outcome among patients with Dukes' C cancer (p=0.024) is particularly noteworthy. On multivariate analysis, KAI1/CD82 expression and Dukes' stage were identified as significant and independent prognostic factors (p=0.006 and 0.045, respectively). CONCLUSION: KAI1/CD82 expression closely correlates with clinicopathological factors for colorectal cancers. KAI1/CD82 expression appears to be a useful prognostic marker.     

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.     

Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases

KAI1 belongs to a structurally distinct family of membrane glycoproteins, which function via cell-cell and cell-extracellular matrix interactions, thereby potentially influencing the ability of cancer cells to invade tissues and to metastasize into lymph nodes and distant organs. In the present study, we examined KAI1 expression in lymph node and liver metastases in comparison with primary pancreatic cancer to evaluate its influence on metastasis. KAI1 mRNA analysis was performed by Northern blot analysis and in situ hybridization. In addition, the respective protein was studied by immunostaining. Fourteen primary pancreatic cancer samples in which no lymph node metastases were present and 25 primary pancreatic cancer samples in which lymph node metastases were present at the time of tumor resection were included. In 20 of these cases, primary pancreatic cancer tissues and corresponding lymph node metastases from the same patient were studied. Furthermore, 11 liver metastases were available for KAI1 analysis. Increased steady-state levels of KAI1 mRNA were found in 33/39 (85%) primary pancreatic cancers in comparison with normal controls. Statistical analysis of KAI1 mRNA levels and clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher in non-metastasized tumors compared with tumors in which lymph node or distant metastases were present. In lymph node metastases KAI1 mRNA expression was lower than in the corresponding primary tumors: In 14 of 20 lymph node metastases no KAI1 mRNA expression and in 6 of 20 lymph node metastases only weak KAI1 mRNA levels were present in some cancer cells. Cancer cells of distant metastases were devoid of or exhibited low KAI1 mRNA levels compared with those of primary pancreatic cancers. A similar pattern was observed by immunostaining. These data support the hypothesis that KAI1 gene expression might influence the metastatic ability of pancreatic cancer cells in vivo. Reduction of KAI1 appears to promote cancer cell spread in lymph nodes and distant organs. Int. J. Cancer (Pred. Oncol.) 79:349–355, 1998. © 1998 Wiley-Liss, Inc.     

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.     

Ⅰ期乳腺癌中KAI1表达与腋淋巴结微小转移的研究

目的探讨Ⅰ期乳腺癌中KAI1蛋白表达与腋淋巴结微小转移的关系。方法 对56例Ⅰ期乳腺癌的原发癌灶用抗KAI1 及常规病理学检查未发现癌转移的840枚腋窝淋巴结用抗上皮细胞膜(抗EMA)分别进行免疫组化染色。结果 KAI1阳性表达率为32.1%(18/56);被检病例的21.4%(12/56)存在淋巴结内癌的微小转移;在非浸润性乳腺癌中KAI1阳性表达率为75.0%(6/8)明显高于浸润性乳腺癌(25.0%;12/48);淋巴结微小转移者KAI1阳性率为8.3%(1/12), 显著低于无转移者(38.6%;17/44)。结论 在乳腺癌转移的早期已经发生KAI1表达下降, 并与肿瘤的侵袭能力密切相关, 该基因表达的变化是临床上推断乳腺癌早期淋巴结转移与否的有用指标。