CD44s、CD44v6在口腔鳞状细胞癌中的表达

目的　研究细胞粘附分子 CD4 4 s及 CD4 4 v6与口腔鳞状细胞癌 ( OSCC)的发生、淋巴结转移的关系。方法　采用免疫组织化学 S- P法对 2 6例口腔鳞癌及其 11例转移淋巴结进行 CD4 4 s、CD4 4 v6的检测。结果　CD4 4 s、CD4 4 v6在口腔鳞癌中的表达较正常鳞状上皮中显著下降 ( P<0 .0 5 ,P<0 .0 0 1) ;高度恶性口腔鳞癌中CD4 4 v6的表达水平较低度恶性者显著降低 ( P<0 .0 1) ;有淋巴结转移的原发灶较无淋巴结转移的原发灶的CD4 4 v6表达水平显著降低 ( P<0 .0 0 1)。结论　 CD4 4 s、CD4 4 v6表达下降在 OSCC的发生中有一定的作用 ;CD4 4 v6表达下降可作为预测 OSCC发生淋巴结转移可能性大小的一个指标。     

CD44v6在口腔鳞状细胞癌中的表达

目的：研究细胞粘附分子CD44v6在口腔鳞状细胞癌中的表达及其与临床参数的关系。方法：采用免疫组织化学S-P法对49例附有癌旁组织的口腔鳞状细胞癌及其中的7例转移淋巴结进行CD44v6的检测。结果：CD44v6表达与肿瘤病理分级有关（P〈0.05）,随着肿瘤分化程度的降低,CD44v6表达呈降低趋势,部分区域甚至不表达;发生淋巴结转移组与未发生淋巴结转移组的原发灶比较,CD44v6表达强度有显著差异（P〈0.01）,发生淋巴结转移组的原发灶CD44v6高表达,未发生淋巴结转移组的原发灶CD44v6低表达。结论：CD44v6的表达与口腔鳞状细胞癌的分化程度有一定相关性;CD44v6高表达有可能作为口腔鳞状细胞癌淋巴转移的一个预测指标。     

路易斯寡糖在口腔黏膜鳞状细胞癌中的表达及其与颈淋巴结转移的关系

目的　探讨内皮细胞选择素(E-selectin)及其配体路易斯寡糖[sialyl Lewis(a)]在口腔黏膜鳞状细胞癌颈淋巴结转移机制中所起的作用。方法　应用免疫组织化学方法检测口腔鳞癌颈清扫术后标本38例E-Selectin及 sialyl Lewis(a)的表达情况,并与颈淋巴结转移发生进行统计学分析。结果　在口腔癌原发灶组织中sialyl Lewis(a) 在颈淋巴结转移组的表达率为79%(15/19),高于无转移组(21%,4/19),两组间比较有显著性差异(P<0·01),E-Se- lectin表达在两组间无显著性差异(P>0·05)。结论　口腔鳞癌细胞sialyl Lewis(a)的表达与颈淋巴结转移可能有关,似可作为口腔癌颈淋巴结转移的预测指标。     

骨桥蛋白及其受体CD44v6在口腔鳞状细胞癌中的定量表达及意义

目的探讨骨桥蛋白（OPN）及其受体CD44v6在口腔鳞状细胞癌（OSCC）中的蛋白定量表达、临床意义及二者之间的关系。方法应用EnVisionTM法检测正常口腔黏膜（n=12）和OSCC患者（n=59）肿瘤组织中OPN和CD44v6的表达,结合图像分析系统进行定量分析,统计不同临床、病理指标下OSCC肿瘤组织中OPN的表达情况以及两种蛋白表达的相互关系。结果OPN在OSCC肿瘤组织中的表达显著高于正常口腔黏膜（P<0.05）。OPN的表达与OSCC不同临床分期、颈淋巴结转移有相关性,在OSCC高分化和中低分化者间差异无统计学意义。CD44v6在OSCC与正常口腔黏膜中差异无统计学意义,且其表达与临床病理指标关系不密切。在OSCC中,OPN与CD44v6表达无显著相关性。结论OPN在OSCC存在过度表达,其表达水平与肿瘤临床分期以及有无淋巴结转移存在一定的相关性,CD44v6与肿瘤临床病理特征无关,而且与OPN表达无相关性。     

Expression of CD44 variant exons by primary and metastatic oral squamous carcinomas

Abnormal CD44 expression in many neoplasms correlates with behaviour, but reports on its role in oral squamous carcinoma are contradictory. CD44 expression was characterised in a closely matched series of oral carcinomas with and without metastases in both frozen and formalin-fixed tissue and correlated with behaviour and histological grading parameters. Eleven primary oral squamous carcinomas without metastases and nine primary carcinomas with 19 matched metastases were stained immunocytochemically for CD44H and products of variant exons v3, v4/5, v6 and v9. Patterns of staining in frozen and formalin-fixed tissue were correlated with invasive front grading and behaviour using exact inferential statistics. Most primary carcinomas stained for all exons tested but some showed loss of expression of v4/5. Loss of expression was more marked in metastases, but there was no correlation between expression and behaviour or grade. Stromal surfaces of epithelial cells often expressed variant exon products reflecting loss of polarity. This, together with selective loss of v4 and v5 in primary carcinomas and their more frequent loss in metastases, suggests that CD44 may play a role in metastasis of some oral squamous carcinomas.     

基质金属蛋白酶-9在口腔鳞癌中的表达及其与癌细胞增殖和转移的关系

目的:探讨基质金属蛋白酶-9(MMP-9)的表达与口腔鳞癌细胞增殖活性和转移的关系。方法:采用免疫组织化学SP法检测40例口腔鳞状细胞癌标本中MMP-9及Ki-67的表达。结果:MMP-9在口腔鳞癌中的表达与淋巴结转移、TNM分期密切相关(P<0.05),而与患者的年龄、性别、肿瘤分化程度无关(P>0.05)。有淋巴结转移、TNM分期为III IV期者MMP-9的表达分别明显高于无淋巴结转移、TNM分期为I II期者(P<0.05)。口腔鳞癌中MMP-9与Ki-67的表达呈正相关(r=0.348,P<0.05)。结论:MMP-9在口腔鳞癌细胞的增殖和转移中起重要作用,可作为判断口腔鳞癌恶性潜能的生物学指标。     

CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells

Background:  Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR-4 by small interfering RNA (siRNA) in oral cancer cells.
Methods:  We generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR-4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR-4 expression and proliferation in 26 OSCC tissue samples.
Results:  CXCR4-knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the control vector-infected cells ( P  <   0.05). The CXCR4-knockdown OSCC cells grew significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector-infected cells ( P  <   0.05). CXCR-4-positive group had significantly higher PCNA labeling index than CXCR-4-negative group in OSCC tissue samples.
Conclusion:  These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.     

CD44v6在舌鳞癌中表达的研究

目的　研究CD44v6与舌鳞癌分化程度、浸润方式和淋巴结转移的关系。方法　应用免疫组化SABC法检测 45例舌鳞癌组织中CD44v6的表达。结果　CD44v6虽有随舌鳞癌侵袭转移能力增强表达逐渐减弱的趋势 ,但其与肿瘤大小、细胞分化程度、浸润方式及淋巴结转移均无关 (P <0 .0 5)。结论　CD44v6在舌鳞癌中的表达与其侵润及转移无关 ,不宜作为临床判断舌鳞癌恶性程度及预后的一个指标。     

CD44V6、MMP-9在舌癌中的表达及其意义

目的：观察CD44V6和MMP-9在舌癌（tongue squarnous cell carcinomas,TSCC）组织中的表达及其与临床病理因素和预后的关系。方法：采用免疫组织化学PV9000法检测60例舌癌、21例转移淋巴结及15例癌旁正常组织中CD44V6和MMP-9的表达。结果：CD44V6在舌癌中的阳性表达率略低于癌旁组织,无显著意义;MMP-9在舌癌中的阳性表达率明显高于癌旁正常组织（P〈0.05）,并与舌癌的组织学分级呈正相关（P〈0.05）;在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）;舌癌中CD44V6和MMP-9表达强阳性者有4例复发（5年内）。结论：CD44V6和MMP-9在舌癌组织中的表达与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。     

细胞角蛋白在口腔鳞癌颈淋巴结中的表达及意义

目的:研究细胞角蛋白在口腔鳞癌颈部淋巴结中的表达,探索其在淋巴结转移中的作用。方法:30例口腔鳞癌患者资料,其中高分化鳞癌23例,低分化鳞癌7例;其中8例术前诊断已发生颈淋巴结转移。将病理报告为阳性的32个淋巴结及152个阴性淋巴结重新切片,应用广谱细胞角蛋白单克隆抗体(AE1/AE3)作为免疫标志物,采用免疫组织化学方法(SP法)检测。结果:经CK(AE1/AE3)单克隆抗体标记后,32个转移淋巴结均呈阳性反应;152个阴性淋巴结,有4例共7个淋巴结内可见CK(AE1/AE3)阳性反应,阳性反应细胞呈单个或呈簇状散在于淋巴结内,淋巴结结构完好。所检出的4例病例中,高分化及低分化鳞状细胞癌各2例,其中2例术前已经发现颈部有肿大淋巴结,7个微转移之淋巴结中,颌下区2个,颈深上4个,颈深中1个。正常淋巴结呈阴性反应。结论:采用广谱细胞角蛋白单克隆抗体CK(AE1/AE3)作为免疫标志物检测隐匿性转移淋巴结,有利于早期发现微小转移灶,为口腔鳞癌的治疗及预后的判断提供依据。     

口腔鳞癌原发灶及淋巴结转移灶中巨噬细胞的检测及意义

目的：通过检测巨噬细胞在口腔鳞癌原发灶、淋巴结转移灶中的浸润情况,探讨其在口腔鳞癌中的功能及意义。方法：采用免疫组化SABC法分别检测CD68和CD34在42例口腔鳞癌、15例淋巴结转移灶和10例口腔正常组织的表达情况。结果：CD68在口腔鳞癌原发灶及淋巴结转移灶中的表达显著高于正常组（P〈0.01）;而且在淋巴结转移灶中的表达显著高于原发灶（P〈0.01）。同时CD34在肿瘤原发灶中的表达显著高于淋巴结转移灶和正常组织（P〈0.01）,而淋巴结转移灶和正常组织之间无显著性差异。结论：巨噬细胞在口腔鳞癌原发灶和淋巴结转移灶中的浸润情况并不一致,在淋巴结转移灶中,巨噬细胞的功能可能与原发灶中有所不同。     

Characterization of 3 oral squamous cell carcinoma cell lines with different invasion and/or metastatic potentials.

PURPOSE: Proteolytic enzymes may confer specific types of invasion and metastasis in patients with oral squamous cell carcinoma (OSCC). The purpose of this study was to determine if OSCC that invades adjacent bone has different proteolytic enzyme expression profiles than OSCC that metastasizes to lymph nodes or distant organs. Three OSCC cell lines, BHY, HSC-3, and HN, with known behavior regarding bone invasion and lymph node and distant metastatic profiles, were evaluated. The characteristics of a control, human normal nasal epithelial cell line (HNEC), and BHY, HSC-3 and HN were evaluated with regard to their expression of the matrix metalloproteinases and cathepsins. MATERIALS AND METHODS: Expressions of proteolytic enzymes including matrix metalloproteinase, MMP-1, MMP-2, MMP-3, MMP-9, extracellular matrix metalloproteinase inducer (EMMPRIN), cathepsin B, and cathepsin L were compared using immunocytochemistry and flow cytometry in 3 OSCC cell lines and HNEC. The cell morphologies of these 4 cell lines were compared using transmission electron microscopy (TEM). RESULTS: All OSCC cell lines showed higher expression of all the proteolytic proteins when compared with HNEC, except the HSC-3 cell line showed no difference in the expression of MMP-9. There was no detectable difference at the expression level of MMP-1, MMP-2, MMP-3, cathepsin B, and cathepsin L in any of the OSCC cell lines. However, MMP-9 and EMMPRIN levels were higher in the BHY cell line. According to electron microscopy, the cells of the HSC-3 cell line were the smallest and least differentiated among the 3 OSCC cell lines. The BHY cell line was the most highly differentiated showing interdigitation and numerous cell junctions. CONCLUSIONS: MMPs play an important role in the invasion and metastasis of oral cancer. MMP-9 might play a more important role than MMP-2 during invasion. Increased expression of MMP-1, MMP-9, and EMMPRIN proteins might be involved in invasion of OSCC to adjacent bone, as they are necessary for the collagen matrix degradation. Increased expression of MMP-3, cathepsin B and L in OSCC might be associated with both invasion and a high incidence of metastasis.     

Gene expression profile changes correlated with lymph node metastasis in oral squamous cell carcinoma

The purpose of this research was to identify biomarkers for predicting cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). We surveyed the expressions of 1289 cancer-related genes in 41 cases of OSCC by cDNA array analysis. We extracted genes upregulated or downregulated in their expression in association with lymph node metastasis. Of 1289 cancer-related genes, we identified 39 genes differentially expressed in OSCC with or without lymph node metastasis. Expression levels of 9 genes were lower, and those of 30 genes were higher, in node-positive cases. The genes expressed at higher levels in node-positive cases included angiogenesis-related molecules, cell adhesion molecules, and proteolytic enzymes. We suggest that these characteristic genes could provide, if verifiable, useful information for predicting the risk of lymph node metastasis in OSCC.     

口腔鳞癌中趋化因子受体CXCR4和CCR7表达及其与临床病理特征的关系

目的检测CXC类趋化因子受体4(chemokine CXC motif receptor 4,CXCR4)和CC类趋化因子受体7(chemokine CCmotif receptor 7,CCR7)在口腔鳞癌(oral squamous cell carcinoma,OSCC)中表达,探讨其与OSCC临床病理特点及颈淋巴结转移的关系。方法采用免疫组化和反转录聚合酶链反应(RT-PCR)检测64例OSCC组织原发灶、39例转移淋巴结组织和10例正常口腔黏膜组织中CXCR4及CCR7的表达,并分析其与临床病理参数的关系。结果 OSCC组织细胞中CXCR4、CCR7蛋白的阳性表达率分别为62.5%、65.6%,明显高于正常口腔黏膜组织细胞(P<0.01),其中有淋巴结转移组表达率分别为74.36%、84.62%,无淋巴结转移组表达率分别为44%、36%,差异均有统计学意义(P<0.05),而CXCR4、CCR7在淋巴结转移灶中的阳性表达率差异无统计学意义(P>0.05)。RT-PCR检测结果也证实,CXCR4及CCR7在OSCC细胞中均有阳性表达。此外,CXCR4及CCR7的表达与肿瘤的分化程度、侵袭程度和TNM分期密切相关(P<0.05),而与年龄、性别和肿瘤大小无关(P>0.05)。结论趋化因子受体CXCR4、CCR7的表达与OSCC侵袭发展和淋巴结转移密切相关。CXCR4、CCR7有可能成为OSCC治疗的新靶点。     

口腔鳞癌nm23—H1基因存在状态和颈淋巴结转移的关系

目的：探讨口腔鳞癌中nm23-H1基因结构变化和表达水平及其和颈淋巴结转移的关系。方法：用PCR法扩增了30例入口腔鳞癌,7例正常口腔粘膜标本及人舌鳞癌细胞系TSCCa和人口腔转移癌细胞系GNM nm23-H1基因,并对PCR产物进行SSCP分析;用原位杂交法检测鳞癌组织及两组细胞株nm23-H1mRNA水平,对其和颈淋巴结转移的关系进行统计学分析,结果：除1例口腔鳞癌外,所有标本均无nm23-H1结构变化。9例有转移的口腔鳞癌组织中有7例nm23-H1mRNA表达阴性,而1例无转移患者只有5例表达阴性,且GNM nm23-H1阳性率低于TSCCa(41.2%对63．1％）,nm23-H1表达与癌转移呈显著负相关（P＜0．01）,nm23-H1表达和组织学分级无关。结论：nm23-H1 mRNA水平的变化不是由基因结构变化导致;nm23-H1基因产物对口腔鳞癌颈淋巴结转称有抑制作用。     

口腔鳞状细胞癌巨噬细胞浸润与VEGF表达关系的研究

目的探讨口腔鳞状细胞癌中肿瘤相关巨噬细胞（TAMS）与血管内皮生长因子（VEGF）表达之间的关系。方法采用免疫组织化学SP法检测10例口腔正常粘膜，40例口腔鳞状细胞癌标本中CD68及VEGF的表达。结果口腔鳞状细胞癌巨噬细胞计数与VEGF表达明显高于正常口腔粘膜（P〈0.01）；VEGF表达与TNM分期及淋巴结转移显著相关（P〈0.05）；巨噬细胞计数与淋巴结转移显著相关（P〈0.05）；巨噬细胞计数与VEGF表达之间呈正相关（r=0.439，P〈0.01）。结论口腔鳞状细胞癌中TAMS和VEGF表达均与肿瘤的生长和转移有关，且二者之间存在正相关关系。     

E-cad和CD44v6在口腔鳞癌中的表达及意义

目的 探讨黏附分子E-cad和CD44v6在口腔鳞癌中的表达及其与口腔颌面部鳞癌病理分级和侵袭转移的关系.方法 采用免疫组织化学抗生蛋白链菌素-生物素标记染色技术,对54例口腔颌面部鳞癌组织和15例口腔颌面部正常组织进行E-cad和CD44v6表达的检测.结果 口腔鳞癌组织E-cad阳性表达率(50.00%)低于口腔正常组织的阳性表达率(86.67%),其差异有统计学意义(P＜0.05);E-cad和CD44v6的阳性表达率随鳞癌分化程度的降低而降低(P＜0.05);有淋巴结转移的鳞癌原发灶与无淋巴结转移的原发灶比较,前者E-cad阳性表达率(21.43%)低于后者(60.00%),其差异有统计学意义(P＜0.05).E-cad的表达与CD44v6的表达具有显著相关性(P＜0.01).结论 E-cad的低表达与口腔颌面部鳞癌病理分级和转移关系密切.CD44v6在低分化鳞癌组织中低表达.E-cad与CD44v6的联合检测可作为口腔鳞癌发生发展和侵袭转移的参考指标.     

E-cad、CD44V6在口腔鳞癌组织中的表达及其相关性研究

目的 :分析E 钙粘蛋白 (E cadherin ,E cad)和CD44V6在口腔黏膜鳞癌及其癌变过程中的表达规律 ,探讨它们的异常表达与口腔黏膜癌变、转移的关系。方法 :采用免疫组织化学SP法分别检测E cad、和CD44V6在 17例正常口腔黏膜、6例口腔黏膜异常增生和 5 2例口腔黏膜鳞癌的不同表达。结果 :其中 ,E cad在正常口腔黏膜、口腔黏膜异常增生的阳性表达率明显高于在口腔黏膜鳞癌中的阳性表达率 ;而CD44V6在正常口黏膜、口腔黏膜异常增生的阳性表达率明显高于在口腔黏膜鳞癌中的阳性表达率 ;同时 ,E cad的阳性表达率随肿瘤的分化程度降低而降低 ,CD44V6的阳性表达率随肿瘤的分化程度降低而升高 ;E cad和CD44V6之间的关系表现为负相关 ,同时 ,CD44V6与肿瘤的转移密切相关。结论 :E cad和CD44V6在口腔黏膜鳞癌的分化和转移过程中起重要作用 ,CD44V6的表达与肿瘤的不良分化和转移密切相关 ,而E cad的表达则对患者有保护趋势。     

人口腔鳞癌演变过程中HLA-DR表达改变的研究

目的 :观察HLA DR在口腔鳞癌发生、发展过程中表达的改变并探讨其临床意义。方法 :采用免疫组织化学的方法检测了 2 6例正常口腔黏膜、8例口腔黏膜白斑、3 2例口腔鳞癌原发灶及 15例颈淋巴结转移灶标本内HLA DR的表达。结果 :口腔鳞癌原发灶与正常口腔黏膜HLA DR的表达存在有显著性差异 (P <0 .0 5) ,其余各组间未见有此差异 ;鳞癌原发灶HLA DR的表达除与局部淋巴细胞浸润有显著性关系外与其余各临床病理资料间均无明显关系。结论 :HLA DR在口腔鳞癌细胞中存在有表达异常增高的现象但并不能作为独立的预后判断因素     

口腔鳞状细胞癌中趋化因子受体CCR7的表达及其与颈部淋巴结转移的关系

目的 探讨趋化因子受体CCR7在口腔鳞状细胞癌中的表达及在口腔鳞癌颈淋巴结定向转移中的作用.方法 应用免疫组化、反转录聚合酶链反应(RT-PCR)和Western blotting等方法检测85例口腔鳞状细胞癌组织以及口腔鳞癌细胞系Tca8113和腺样囊性癌细胞系(adenoid cysticcareinoma,ACC-M)中CCR7的表达,分析CCR7表达与口腔鳞癌临床病理参数之间的关系.比较Tca8113和ACC-M对淋巴结的黏附能力,以及CCR7抗体对其黏附能力的影响.结果 66%(56/85)的口腔鳞癌组织存在CCR7的阳性表达,其中淋巴结转移组的CCR7阳性表达率明显高于无淋巴结转移组(P=0.015).RT-PCR和Western blotting检测结果也证实,CCR7在口腔鳞癌中有阳性表达.Tca8113细胞系对淋巴结的黏附能力明显高于ACC-M细胞系,并且能够被CCR7抗体有效阻断.结论 趋化因子受体CCR7在口腔鳞癌的发生发展及淋巴结转移中起着重要的作用.