c-erbB-2癌基因在粘液表皮样癌中的表达

ｃ－ｅｒｂＢ－２癌基因在粘液表皮样癌中的表达王洁董福生王小玲尤红煜王永军我们采用ｃ－ｅｒｂＢ－２癌基因蛋白研究粘液表皮样癌，以探讨其在肿瘤中的过度表达及其在与腺癌鉴别诊断中的意义。１．材料与方法：从存档资料中挑选出涎腺粘液表皮样癌４２例（高分化２２例...     

涎腺肿瘤中c-erbB-2癌基因扩增及蛋白产物过度表达的研究

作者采用ＤＮＡ斑点杂交及免疫组织化学方法对２８５例涎腺肿瘤石腊包埋组织中ｃ－ｅｒｂＢ－２癌基因扩增及蛋白产物过度表达进行检测．结果表明：涎腺恶性肿瘤及多形性腺瘤有不同程度的ｃ－ｅｒｂＢ－２癌基因扩增,其中癌在多形性腺瘤中扩增率２０／３０（６６．６７％）,腺癌为１３／２０（６５．００％）,明显高于其它肿瘤（ｐ＜０．０５）．ｃ－ｅｒｂＢ－２蛋白产物过度表达出现在癌在多形性腺瘤中１６／３０（５３．３３％）、腺癌１１／２０（５５．００％）、肉瘤１／１０（１０．００％）及多形性腺瘤中５／３５（１４．２９％）,癌在多形性腺癌中及腺癌表达率明显高于其它肿瘤（ｐ＜０．０５）．提示：ｃ－ｅｒｂＢ－２癌基因可能与涎腺肿瘤细胞分化程度有关,在部分肿瘤的发生、发展过程中起一定的作用。     

涎腺肿瘤中c-erbB-2癌基因扩增及蛋白产物过度表达的研究

作者采用ＤＮＡ斑点杂交及免疫组织化学方法对２８５例涎腺肿瘤石腊包埋组织中ｃ－ｅｒｂＢ－２癌基因扩增及蛋白产物过度表达进行检测．结果表明：涎腺恶性肿瘤及多形性腺瘤有不同程度的ｃ－ｅｒｂＢ－２癌基因扩增,其中癌在多形性腺瘤中扩增率２０／３０（６６．６７％）,腺癌为１３／２０（６５．００％）,明显高于其它肿瘤（ｐ＜０．０５）．ｃ－ｅｒｂＢ－２蛋白产物过度表达出现在癌在多形性腺瘤中１６／３０（５３．３３％）、腺癌１１／２０（５５．００％）、肉瘤１／１０（１０．００％）及多形性腺瘤中５／３５（１４．２９％）,癌在多形性腺癌中及腺癌表达率明显高于其它肿瘤（ｐ＜０．０５）．提示：ｃ－ｅｒｂＢ－２癌基因可能与涎腺肿瘤细胞分化程度有关,在部分肿瘤的发生、发展过程中起一定的作用．     

涎腺腺样囊性癌c—erbB—2癌基因蛋白的研究

采用ｃ－ｅｒｂＢ－２癌基因蛋白抗体，对３４例涎腺腺样囊性癌（包括筛孔型，管状型，实性型）进行免疫组化染色，结果显示，涎腺腺样囊性癌３种组织学类型均过度表达ｃ－ｅｒｂＢ－２癌基因，经统计学分析表明，筛孔型与管状型涎腺腺样囊性癌的ｃ－ｅｒｂＢ－２癌基因表达差异有显著性（Ｐ〈０．０５），提示ｃ－ｅｒｂＢ－２癌基因的过度表达与肿瘤的分化及恶性程度关系密切。     

癌基因c－erbB－2、抗癌基因p53在涎腺良恶性肌上皮瘤中的表达及分析

应用免疫组化方法对４０例涎腺肌上皮瘤（ＭＥ）、肌上皮瘤细胞生长活跃（ＭＡＰ）、恶性肌上皮瘤（ＭＭＥ）进行了ｃ－ｅｒｂＢ－２、ｐ５３基因蛋白表达的研究。结果：ｃ－ｅｒｂＢ－２表达总的阳性率为４２．５％（１７／４０），其中ＭＥ为１６．７％（２／１２）．ＭＡＰ为３７．５％（３／８），ＭＭＥ为６０％（１２／２０），三者间有显著差异（Ｐ＜０．０５），ｐ５３表达总的阳性率为２５％（１０／４０），ＭＥ，ＭＡＰ，ＭＭＥ三者间无显著差异（Ｐ＞０．０５）．ｃ－ｅｒｂＢ－２与ｐ５３在该瘤中的表达无相关性，结果表明ｃ－ｅｒｂＢ－２和ｐ５３的过量表达可能参与了涎腺肌上皮瘤的发生和分化过程；特别是癌基因ｃ－ｅｒｂＢ－２的检测对鉴别该瘤的良、恶性及早期诊断有一定的意义。     

涎腺腺样囊性癌c─erbB─2癌基因蛋白的研究

采用ｃ－ｅｒｂＢ－２癌基因蛋白抗体，对３４例涎腺腺样囊性癌（包括筛孔型、管状型、实性型）进行免疫组化染色。结果显示：涎腺腺样囊性癌３种组织学类型均过度表达ｃ－ｅｒｂＢ－２癌基因。经统计学分析表明，筛孔型与管状型涎腺腺样囊性癌的ｃ－ｅｒｂＢ－２癌基因表达差异有显著性（Ｐ＜０．０５）。提示ｃ－ｅｒｂＢ－２癌基因的过度表达与肿瘤的分化及恶性程度关系密切。     

涎腺肌上皮瘤与肌上皮癌中c—erbB—2癌基因的表达与p53基因突…

为了探讨癌基因在肌上皮肿瘤中的过度表达及其意义，作者采用ｃ－ｅｒｂＢ－２癌基因蛋白与ｐ５３基因蛋白的单抗（ＤＯ－１）研究１４例肌上皮瘤与６例肌上皮癌。结果发现，５／６例肌上皮癌与９／１４例肌上皮瘤均过度表达ｃ－ｅｒｂＢ－２癌基因蛋白；５例瘤旁腺体内导管上皮细胞也过度表达ｃ－ｅｒｂＢ－２。因此推测，ｃ－ｅｒｂＢ－２癌基因可能作为一种启动基因，与肌上皮肿瘤的发生有着密切的联系。ｐ５３基因蛋白研究发现，     

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。     

癌基因c—erbB—2,抗癌基因p53在涎腺良恶性肌上皮瘤中 …

应用免疫组化方法牟４０例涎腺肌上皮瘤，肌上皮瘤细胞生长活跃，恶性肌上皮瘤进行了ｃ－ｅｒｂＢ－２，ｐ５３基因蛋白表达的研究，结果：ｃ－ｅｒｂＢ－２表达总的阳性率为４２．５％，其中ＭＥ为１６．７％，ＭＡＰ为３７．５％，ＭＭＥ为６０％，三者间有显著差异。     

涎腺肌上皮瘤与肌上皮癌中c－erbB－2癌基因的表达与p53基因突变的研究

为了探讨癌基因在肌上皮肿瘤中的过度表达及其意义，作者采用ｃ－ｅｒｂＢ－２癌基因蛋白与ｐ５３基因蛋白的单抗（ＤＯ－１）研究１４例肌上皮瘤与６例肌上皮癌。结果发现，５／６例肌上皮癌与９／１４例肌上皮瘤均过度表达ｃ－ｅｒｂＢ－２癌基因蛋白；５例瘤旁腺体内导管上皮细胞也过度表达ｃ－ｅｒｂＢ－２。因此推测，ｃ－ｅｒｂＢ－２癌基因可能作为一种启动基因，与肌上皮肿瘤的发生有着密切的联系。ｐ５３基因蛋白研究发现，肌上皮癌（５／６例）反应阳性，肌上皮瘤（０／１４例）全部反应阴性。作者认为，ｐ５３基因突变可能在肌上皮癌的形成过程中起着重要作用     

p53、C-erbB-2癌基因蛋白在涎腺粘液表皮样癌中的表达及其临床病理学意义

目的探讨癌基因蛋白p53、C-erbB-2（p185）过度表达与粘液表皮样癌生物学行为的关系。方法利用微波免疫组织化学方法对32例人粘液表皮样癌的癌基因蛋白p53、C-erbB-2进行检测。结果正常诞腺组织p53、C-erbB-2均为阴性反应。癌旁导管上皮细胞两者阳性率分别为10.0％及15.0％,但腺泡细胞阴性。粘波表皮样癌组织中p53、C-erbB-2阳性率分别为40.6％及46.9％。p53、C-erbB-2在粘液细胞、表皮样细胞及中间细胞内均有表达。p53、C-erbB-2的表达与粘液表皮样癌肿瘤组织学类型、分化程度及肿瘤复发等肿瘤生物学行为密切相关（P＜0.01）。结论p53、C-erbB-2可作为粘液表皮样癌的分化性标志物,用于监测病情、判断预后等。     

Elevated serum levels of a c-erbB-2 oncogene product in oral squamous cell carcinoma patients

OBJECTIVES: Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in many kinds of cancer including oral squamous cell carcinoma (OSCC). In order to obtain further information on the c-erbB-2 gene product p185, it is necessary to quantify expression levels. In this study we used an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of OSCC patients. METHOD: Sera from 84 OSCC patients, 51 breast cancer patients (as positive controls), and 15 healthy controls were assayed in an ELISA. To study c-erbB-2 overexpression in OSCC, and breast cancer tissue samples we used an immunohistochemical technique. RESULTS: The mean serum value (ng/ml, mean/SD) for the normal controls was 8.46/1.29. We chose the 95% level of normal controls as a cut-off to distinguish individuals with elevated levels. The breast cancer patients' and OSCC patients' serum values were 13.83/6.82 and 13.1/4.56, respectively. Significant differences (P < 0.0001) were observed between normal control and OSCC, normal control and the breast cancer group. Immunohistochemically detectable p185 (intermediate to high) was noted in 30 of 61 OSCC, and 24 of 51 breast cancer patients. There was a trend of association of serum oncoprotein fragment levels with tumor stages, but not with tumor sizes, nodal stages, metastases, and oral habits including betel quid chewing, alcohol drinking and smoking in the OSCC group. CONCLUSION: The results of the present study raise the possibility that soluble c-erbB-2 protein levels in serum is a useful parameter for monitoring the disease status as well as the effect of therapy on patients with OSCC.     

Valuation of exfoliative cytology as prediction factor in oral mucosa lesions

The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.     

Expression of cell cycle and apoptosis-related proteins in sporadic odontogenic keratocysts and odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome.

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin D1 with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.     

p53, mdm2, and p21 expression in oral squamous cell carcinomas: relationship with clinicopathologic factors

OBJECTIVE: The purpose of this study was to clarify the correlation of expression of cell cycle-associated gene proteins with clinicopathologic factors in oral squamous cell carcinoma (SCC). STUDY DESIGN: Formalin-fixed paraffin-embedded tissues from 69 oral SCC cases and 10 normal mucosa cases were stained by immunohistochemistry (IHC) for p53, mdm 2, and p21 proteins. RESULTS: We found p53, mdm 2, and p21 expression in 44 of 69 (63.8%), 25 of 69 (36.2%), and 37 of 69 (53.6%) oral SCCs, respectively. Ki-67-labeling index of combined p53(+)/mdm 2(+) expression cases was significantly higher than those that lacked combined expression (P =.004). Combined p53(+)/p21(+) expression showed a significant association with lymph node metastasis (P =.019). In survival analysis, combined p53(+)/p21(+) and p53(+)/mdm 2(+)/p21(+) expression was associated with poor clinical outcome (P =.018 and.012, respectively). CONCLUSION: Combined p53/mdm 2 expression was associated with tumor proliferation in oral SCC. Combined p53/p21 and p53/mdm 2/p21 expression may be a predictive factor in lymph node metastasis.     

口腔鳞癌组织中Ki-67和p53蛋白的表达

目的 探讨口腔鳞癌组织中Ki-67和p53蛋白的表达及其与临床病理特征的关系。方法采用免疫组织化学S-P法对10例正常口腔黏膜组织、16例口腔白斑（OLK）组织、48例口腔鳞癌（OSCC）组织中的Ki-67和p53蛋白表达进行检测,结合患者临床病理资料进行分析,使用SPSS17.0 软件包对数据进行统计学处理。结果Ki-67蛋白在正常口腔黏膜组织、口腔白斑和口腔鳞癌组织中的阳性表达率分别为30.0%、56.3%和79.2%;p53的阳性表达率分别为0.0%、43.8%和70.8%,Ki-67和p53在正常黏膜组与口腔白斑和口腔鳞癌组差异均具有显著性（P<0.05）;Ki67蛋白在口腔鳞癌组织中的表达与肿瘤的临床分期、分化程度、有无淋巴结转移有关（P<0.05）,p53蛋白的表达与肿瘤的分化程度有关(P<0.05);Ki-67和p53蛋白在口腔鳞癌组织中的表达呈正相关（P<0.05）。结论Ki-67和p53蛋白在口腔鳞癌组织中高表达,可能在口腔鳞癌的发生、发展过程中起着重要作用。     

Immunohistochemical localization of CEA,EMA and keratin in salivary mucoepidermal carcinoma]

Localizations of CEA,EMA and keration in 19 cases of mucoepidermal carcinomas were investigated using the indirect immunoperoxidase technique.The results showed CEA was negative in normal salivary glands and showed faint reaction in glands near carcinoma tissue.Keratin and EMA were localized in some myoepithelial cells.The positive rates in carcinoma tissue were 78.9%,89.5% and 84.2%,respectively.The positive rates and staining intensity of CEA and EMA in carcinoma tissue gradually decreased with the decline of tumor differentitation,but that of keratin showed no variation.the author consider that CEA and EMA could become good indices in clinically diagnosing mucoepithelial carcinoma and determining tumor differentiation type cell in mucoepidermal carcinoma and have a potential to multiply express the tumor elements of epithelium and/or mesenchyma.