口腔鳞状细胞癌中COX-2、VEGF和EGFR的表达及意义

目的 研究环氧化酶-2（COX-2）、血管内皮生长因子（VEGF）、表皮生长因子受体（EGFR）在口腔鳞状细胞癌中的表达及相互关系。方法 应用免疫组织化学SP法检测28例口腔鳞状细胞癌组织、15例正常口腔粘膜组织中COX-2、VEGF、EGFR蛋白的表达情况。结果 口腔鳞状细胞癌组织中COX-2的高表达率为60．71％，与正常口腔粘膜的表达比较有统计学意义，但与患者的性剐，年龄，肿瘤的部位及病理学分级无关（P〉0．05）。在口腔鳞状细胞癌中VEGF的阳性表达率为53．57％。EGFR高染表达率为67．86％，均与COX-2表达成正相关趋势（P〈0．05）。结论 COX-2蛋白可能在口腔鳞状细胞癌的发生发展中起作用。并且与VEGF、EGFR的表达成正相关趋势，VEGF、EGFR可能是COX-2在口腔鳞状细胞癌发生发展作用机制中的环节。     

口腔鳞癌增殖细胞核抗原表达及其临床意义

目的：检测口腔鳞状细胞癌中增殖细胞核抗原（ＰＣＮＡ）的表达，探讨与鳞癌预后相关的因素。方法：采用免疫组化的方法，利用ＰＣＮＡ的单克隆抗体检测４４例口腔鳞癌组织中ＰＣＮＡ的表达。结果：低分化鳞癌较高分化鳞癌ＰＣＮＡ的表达明显增强（Ｐ＜０．０５）；晚期鳞癌中ＰＣＮＡ阳性细胞百分率比早期鳞癌显著增高（Ｐ＜０．０５）；ＰＣ－ＮＡ高表达者的淋巴结转移倾向大于ＰＣＮＡ低表达者。结论：ＰＣＮＡ标记可以作为判断鳞癌预后的参考指标。     

口腔鳞状细胞癌血清中IL-18的检测及其病理、临床意义

目的 检测IL-18在口腔鳞状细胞癌（oral cavity squamous cell carcinoma，OCSCC）患者血清中的表达，探讨其与口腔鳞状细胞癌的相关性。方法 应用酶联免疫反应（enzyme-linked immunosorbent assay，ELISA）方法检测30例口腔鳞状细胞癌和10例正常对照血清中IL-18的表达水平。结果 口腔鳞状细胞癌患者血清中IL-18表达水平高于对照组（P〈0．05）；中、低分化，临床Ⅲ、Ⅳ期，颈淋巴结转移者明显高于高分化，Ⅰ、Ⅱ期，无淋巴结转移者（P〈0．05）；不同年龄、性别、肿瘤发生部位，IL-18表达无差异（P〉0．05）。结论 IL-18的表达水平与口腔鳞状细胞癌的病理分级、临床分期及淋巴结转移密切相关。     

口腔鳞癌组织超氧化物歧化酶免疫组化定位观察

作者对７０例口腔鳞状细胞癌组织标本进行超氧化物歧化酶（ＳＯＤ）免疫组化研究（ＡＢＣ法）。结果发现，鳞癌组织中ＳＯＤ标记阳性率和阳性程度均显著高于癌旁和正常上皮组织（Ｐ＜０．００１）；癌组织分化程度越差，其ＳＯＤ标记阳性率和阳性程度亦越高（Ｐ＜０．０５）；高分化舌癌的ＳＯＤ阳性率和阳性程度较高分化唇癌为高（Ｐ＜０．０５）。结果表明：①本研究方法具有定位及半定量特点，特异性及灵敏度高，组织对比性好，检测误差少，结果判断可靠等优点。②口腔鳞癌组织的生物学特性，分化程度及预后与ＳＯＤ含量增高有关。     

Wnt信号传导通路组成蛋白与口腔鳞状细胞癌的分化和增殖

目的研究信号传导通路组成蛋白Writ-1、β-连环蛋白（β-catenin）和腺瘤样结肠息肉病（adenomatous polyposis coli，APC）基因在口腔鳞状细胞癌中的表达，探讨它们在口腔鳞状细胞癌分化和增殖中的作用。方法免疫组织化学法检测66例不同分化程度的口腔鳞状细胞癌中Wnt-1、β-连环蛋白、APC基因及MIB-1的表达。结果37例高分化口腔鳞状细胞癌中分别有30、25和31例高表达Wnt-1、APC和β-连环蛋白，7、12和6例低表达Wnt-1、APC和β-连环蛋白；29例中、低度分化口腔鳞状细胞癌中分别有6、9和11例高表达Wnt-1、APC和β-连环蛋白，23、20和18例低表达Wnt-1、APC和β-连环蛋白；66例口腔鳞状细胞癌中MIB-1有34例低表达，32例高表达。Wnt-1、β-连环蛋白和APC的表达与MIB-1和口腔鳞状细胞癌的组织学分级差异有统计学意义（P〈0．01）。结论Wnt-1、APC和β-连环蛋白在口腔鳞状细胞癌的分化和增殖中起重要作用。     

TRAIL在口腔鳞状细胞癌和白斑中的表达及意义

目的：研究肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis inducing ligand,TRAIL）在口腔鳞状细胞癌（OSCC）组织及白斑中的表达及意义。方法：采用免疫组化Maxvision两步法检测54例口腔鳞状细胞癌、30例口腔黏膜白斑、22例正常口腔黏膜组织中TRAIL的表达水平。结果：TRAIL在口腔鳞状细胞癌组织和黏膜白斑中的表达水平均低于其在正常口腔黏膜中的表达水平（P〈0.05）,分别为33.3%、56.7%、86.4%,其在癌组织与白斑中表达水平的差异无统计学意义。TRAIL在高分化癌组织中的表达水平高于中低分化组（P〈0.05）。TRAIL在不同临床分期组间及淋巴结转移与非转移组间表达水平的差异无统计学意义。结论：TRAIL表达的抑制可能与口腔鳞状细胞癌及口腔黏膜白斑的发生有关,并且TRAIL可能参与了初始阶段的正常黏膜向癌组织的转化。TRAIL在口腔鳞状细胞癌中的表达水平与癌组织的分化程度相关。     

Caspase-3在口腔粘膜癌前病变及鳞状细胞癌中的表达研究

目的：初步探讨Caspase-3在口腔正常粘膜、上皮单纯性增生、上皮异常增生和鳞状细胞癌组织中的表达及意义。方法：采用SABC免疫组织化学方法检测正常口腔粘膜（10例），上皮单纯性增生（8例），上皮异常增生（20例）,鳞状细胞癌（32例）中Caspase-3的表达。结果：各阶段均有Caspase-3的表达，但表达强度不同。Caspase-3在正常口腔粘膜组织中弱表达于基底细胞至基底上细胞或表层细胞浆或／和胞核。上皮异常增生中随异常增生程度的增高Caspase-3表达增强。鳞状细胞癌组中Caspase-3表达明显低于正常组（P＜0．05）和上皮异常增生组（P＜0．01），且Caspase-3在高分化鳞状细胞癌中表达明显高于低分化鳞状细胞癌组（P＜0．05）。结论：Caspase-3表达水平代偿性高是口腔癌前病损发生发展中的早期事件。Caspase-3在鳞状细胞癌中表达下降，促进肿瘤细胞异常增殖的同时，进一步抑制细胞凋亡，导致鳞状细胞癌最终的发生和发展。     

增殖细胞核抗原和p53蛋白在涎腺肿瘤中的表达

为了研究增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）和ｐ５３在涎腺肿瘤中的表达，作者用抗ＰＣＮＡ及ｐ５３单克隆抗体对良、恶性混合瘤及粘液表皮样癌组织标本进行了免疫组化染色。结果表明，恶性混合瘤ＰＣＮＡ增殖指数较高，与混合瘤细胞生长活跃型及混合瘤相比差异有极显著性（Ｐ＜０．０１）；低分化粘液表皮样癌的ＰＣＮＡ阳性表达明显高于高分化型（Ｐ＜０．０１）。ｐ５３在恶性混合瘤中阳性表达率高（６０．０％），与粘液表皮样癌（２０．０％）相比差异有显著性（Ｐ＜０．０５）。另外，我们观察到ｐ５３阳性表达的肿瘤组织ＰＣＮＡ增殖指数较高。结论：ＰＣＮＡ增殖指数可以作为支持诊断恶性混合瘤的指标；是粘液表皮样癌组织学分级的重要参数。ｐ５３蛋白是恶性混合瘤的有效标记物；ｐ５３蛋白参与ＰＣＮＡ表达的调节。     

表皮生长因子受体在颊粘膜鳞状细胞癌中的表达及其临床病？…

表皮生长因子受体（ＥＧＦＲ）是一单跨膜糖蛋白，与细胞的增殖、转化有关。本文采用免疫组化ＡＢＣ检测８例正常颊粘膜上皮及４０例颊粘膜鳞癌中ＥＧＦＲ的表达状况，结果显示：ＥＧＦＲ在颊癌组织中呈异质性表达，其阳性率明显高于正常颊粘膜组织（Ｐ〈０．０５）；ＥＧＦＲ表达状况与颈淋巴结转移及预后间存在相关关系（Ｐ〈０．０５）。ＥＧＦＲ（＋）表达者多数伴有颈淋巴结转移，预后差。以上结果说明，ＥＧＦＲ在颊癌组织中的     

MDC1蛋白在口腔鳞状细胞癌中的表达及意义

目的：探讨口腔鳞状细胞癌中MDC1（mediator of DNA damage cheekpoint protein1）蛋白的表达水平及意义。方法：采用免疫组织化学Envision法检测10例正常口腔黏膜、60例口腔鳞状细胞癌中MDC1的表达水平．并分析其与临床病理参数之间的关系。结果：MDC1蛋白在口腔鳞状细胞癌中表达高于正常口腔黏膜，两者之间差异有统计学意义（P=0．042），而且MDC1蛋白的表达升高与淋巴结转移有关（P=0．033），但与病理分级（P=0．986）、患者的年龄（P=0．723）、性别（P=0．142）无关。结论：MDC1蛋白在口腔鳞状细胞癌中表达增高，提示它可能在肿瘤的发生和发展中具有一定的作用，为进一步理解细胞DNA损伤与肿瘤发生的关系提供了依据。     

Evaluation of epidermal growth factor receptor in squamous cell carcinoma of the oral cavity.

Forty-seven cases of oral squamous cell carcinoma were examined immunohistochemically by the avidin-biotin peroxidase complex method with anti-epidermal growth factor (EGF) receptor mouse monoclonal antibody, and 24 cases (51%) were shown to have EGF receptor-positive cells. Correlation was strong between presence of EGF receptors and differentiation; the EGF receptor-positive cells were differentiated, whereas poorly differentiated tumors exhibited less intense staining. EGF receptor gene and c-erb B-1 by Southern blot analysis disclosed that one of 25 cases of squamous cell carcinoma exhibited a fourfold amplification of the gene.     

TGFβ1mRNA在颌骨骨折愈合过程中的表达及意义

为了进一步探讨ＴＧＦβ在骨生长和骨愈合中的作用，建立了颌骨骨折愈合的动物模型，利用原位杂交方法检测骨折愈合过程中ＴＧＦβ１ｍＲＮＡ的表达。结果发现，在骨折愈合过程中的软骨形成和膜内骨骨化阶段，ＴＧＦβ１的转录水平较高，在膜内成骨时转录水平较低，而在伤后即刻反应阶段无ＴＧＦβ１的转录。说明ＴＧＦβ在骨折修复过程中最初的形态发生，随后的细胞增殖及最终的组织重建中起着重要的作用。     

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目的：探讨表皮生长因子受体（EGFR）在口腔鳞状细胞癌（OSCC）中的蛋白表达与基因扩增,并评估其在OSCC发生、发展和预后中的价值。方法以石蜡包埋组织芯片为材料,分别采用免疫组化SP法与荧光原位杂交（FISH）技术,检测辽宁省人民医院2003年1-6月手术切除并经病理确诊为OSCC存档石蜡包埋组织蜡块103例及30例正常口腔黏膜组织中的EGFR蛋白表达及基因扩增。结果 EGFR蛋白在OSCC、正常口腔黏膜组织中表达的阳性率分别为42.7%和3.3%;扩增阳性率分别为31.1%和0;OSCC中EGFR蛋白表达、基因扩增阳性率与正常口腔黏膜组织比较,差异有统计学意义（P＆lt;0.05）;在OSCC组织中EGFR蛋白表达、基因扩增阳性率与患者年龄、性别、肿瘤大小、分化程度等均无相关性（P＆gt;0.05）,与肿瘤淋巴结转移、临床分期相关（P＆lt;0.05）。结论EGFR与OSCC的发生、发展有关,可将其作为判断OSCC生物学行为的重要参考指标。     

EGFR and PCNA expression in oral squamous cell carcinomas--a valuable tool in estimating the patient's prognosis

We investigated 100 cases of oral squamous cell carcinomas immunohistologically with respect to the expression of the epidermal growth factor receptor (EGFR) and the proliferating cell nuclear antigen (PCNA). The results were correlated with a new malignancy grading of the invasive tumour areas and the clinical outcome of the patients to estimate the individual prognosis. In conclusion, the amount of antigen expression of both antigens increases with the increasing grade of malignancy of the oral squamous cell carcinoma. Furthermore, there is a statistically significant correlation between the amount of antigen expression and the patient's prognosis. An overexpression of EGFR and PCNA is associated with a short survival of the patient. Both antigens detect relevant tumour biological parameters and are worthy factors in estimating the individual prognosis in patients suffering from oral squamous cell carcinomas.     

Pharmacodiagnostic evaluation of EGFR expression in oral squamous cell carcinoma

OBJECTIVE: To determine epidermal growth factor receptor (EGFR) expression in oral squamous cell carcinomas (OSCC), and its possible relationships with clinical findings, histological findings, disease course and prognosis. MATERIALS AND METHODS: Surgical specimens of 47 OSCCs were studied immunohistochemically for detection of EGFR using a standardized immunohistochemical detection system (EGFR PharmaDx kit). Statistical analysis was used to investigate possible relationships between EGFR expression and clinical findings, histological findings, cell proliferation (MIB1 labelling index), disease course and patient survival. RESULTS: Epidermal growth factor receptor expression was absent or weak in 12 cases (25.5%) and moderate or intense in 35 cases (74.5%). However, EGFR expression did not show statistically significant associations with any of the clinical, histological, biological or prognostic variables considered. CONCLUSION: First, despite previous suggestions that EGFR is a useful indicator of biological tumour behaviour, the present results suggest that EGFR is not a useful indicator of prognosis in OSCC. Secondly, the high prevalence of EGFR overexpression suggests that the possibility of anti-EGFR therapy in OSCC merits further investigation.     

Downregulation of Notch1 and its potential correlation with epidermal growth factor receptor signalling in tongue squamous cell carcinoma

We investigated the expression of Notch1 in human oral squamous cell carcinoma (SCC) and explored its potential correlation with epidermal growth factor receptor (EGFR) signalling in oral SCC. Paraffin sections of primary SCC of the tongue and normal mucosa were screened immunohistochemically for Notch1 and EGFR proteins. Human SCC of the tongue Tca8113 cells were treated with AG1478 to block EGFR signalling, and were transfected with the vector that encodes the specific short hairpin RNA (shRNA) that targets EGFR. In SCC of the tongue expression of Notch1 was cancelled except in sites of squamous metaplasia where it was raised, while expression of EGFR was found in the peripheral cells of carcinomas, but not in sites of squamous metaplasia. In normal tongue mucosa, Notch1 was expressed mainly in the stratum corneum, but not in the stratum basale, while EGFR was expressed mainly in the stratum basale, but not in the stratum granulosum or stratum corneum. The blocking of EGFR signalling or the silencing of the EGFR gene resulted in upregulation of Notch1 at mRNA and protein levels in Tca8113 cells. These observations suggest that downregulation of Notch1 in oral SCC may be associated with upregulation of EGFR signalling.     

Expression of epidermal growth factor receptor on oral squamous cell carcinoma

The expression of the receptor for epidermal growth factor (EGF) in normal oral mucosa, papillomas and squamous cell carcinoma (SCC) has been determined by immunohistology and autophophorylation studies. Immunoreactive receptor was localised using two antibodies which recognise the receptor; EGFR1 which reacts with sequences in the external domain of the receptor and F4 which recognises sequences in the internal domain. EGFR was present on basal, suprabasal and some spinous cells of normal oral mucosa. Regional variation in the distribution of receptor was apparent. A similar pattern of receptor expression was seen on oral papillomas. The distribution and intensity of epidermal growth factor receptor (EGFR) expression varied between 20 patients with oral SCC. The staining patterns seen with the two antibodies were similar on all tissue types. The protein tyrosine-kinase activity of the receptor present on eight oral SCC was also examined by immunoprecipitation and autophosphorylation studies. This procedure also demonstrated variations in the amount of functional EGFR in these tumours. There was no significant correlation between the level of EGFR expression and tumour behaviour.     

口腔白斑组织中表皮生长因子受体的表达

本文应用抗表皮生长因子受体（EGFR）多克隆抗体，采用S－P免疫组化方法，对10例正常口腔粘膜组织，20例上皮单纯增生性白斑，14例上皮异常增生性白斑，21例口腔鳞癌组织进行研究。结果提示，口腔白斑组织中EGFR的异常表达与口腔白斑上皮异常增和癌变有关，作者认为EGFR的异常表达可能是口腔白斑恶变的较好的标志。     

成纤维细胞生长因子受体3在头颈部鳞癌中的表达及其意义

目的 探讨成纤维细胞生长因子受体3(FGFR3)在头颈部鳞癌中的表达状况及其与头颈部鳞癌分化程度的相关性。方法 采用免疫组化方法,检测FGFR3在正常口腔黏膜上皮和40例头颈部鳞癌(其中高分化鳞癌21例,中分化鳞癌16例,低分化鳞癌3例)中的表达状况。结果 FGFR3在头颈部鳞癌中呈阳性表达;高分化鳞癌细胞中FGFR3表达较强,低分化鳞癌细胞中FGFR3表达较弱;而角化中心则无FGFR3表达。正常口腔黏膜上皮中FGFR3呈阴性表达。结论 FGFR3可能与头颈部鳞癌的发病机制有关;FGFR3的表达状况与头颈部鳞癌分化程度有一定的相关性。     

Impact of epidermal growth factor receptor,mesenchymal–epithelial transition factor,and insulin-like growth factor receptor 1 expression on survival of patients with oral and oropharyngeal cancer

The aim of this study was to evaluate the impact of expression of epidermal growth factor receptor (EGFR), mesenchymal–epithelial transition factor (c-Met), and insulin-like growth factor receptor 1 (IGF-1R) protein on response to treatment and survival in patients with oral and oropharyngeal squamous cell carcinoma (SCC). EGFR, c-Met, and IGF-1R immunohistochemical (IHC) scores were generated based on the incidence and intensity of expression of the biomarkers evaluated in paraffin-embedded sections of biopsy specimens taken before treatment from 113 patients given neoadjuvant chemoradiotherapy followed by resection for primary locally advanced oral and oropharyngeal SCC. Correlations were assessed between the IHC of the biomarkers and the patients’ clinicopathological variables using Spearman's rank test. Cox's regression models were used to evaluate the impact of EGFR, c-Met, and IGF-1R, expression on survival.