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．     

c—erbB—2的表达与涎腺恶性多表性腺瘤预后的关系

本研究的目的在于观察癌基因ｃ－ｅｒｂＢ－２表达与涎腺恶性多形性腺瘤患者预后的关系。采用抗ｃ－ｅｒｂＢ－２癌蛋白单克隆抗体ＡＢ－３，应用免疫组织化学方法，对６０例涎腺恶性多形性腺瘤中心ｃ－ｅｒｂＢ－２癌基因表达产物进行了检测。结果发现，２５例ＭＰＡＪｃ－ｅｒｂＢ－２表达产物阳性，阳性表达率４１．６７％。结合临床随访资料分析，ＭＰＡ复发组ｃ－ｅｒｂＢ－２阳性表达率明显高于未复发组（Ｐ＜）．０５）；ｃ－     

c－erbB－2的表达与涎腺恶性多形性腺瘤预后的关系

本研究的目的在于观察癌基因ｃ－ｅｒｂＢ－２表达与涎腺恶性多形性腺瘤患者预后的关系。采用抗ｃ－ｅｒｂＢ－２癌蛋白单克隆抗体ＡＢ－３，应用免疫组织化学方法，对６０例涎腺恶性多形性腺瘤中ｃ－ｅｒｂＢ－２癌基因表达产物进行了检测。结果发现，２５例ＭＰＡ显示ｃ－ｅｒｂＢ－２表达产物阳性，阳性表达率４１．６７％。结合临床随访资料分析，ＭＰＡ复发组ｃ－ｅｒｂＢ－２阳性表达率明显高于未复发组（Ｐ＜０．０５）；ｃ－ｅｒｂＢ－２表达阳性患者术后５年生存率明显低于表达阴性者（Ｐ＜０．０５）。表明ｃ－ｅｒｂＢ－２癌基因表达与ＭＰＡ患者的预后密切相关，检测ｃ－ｅｒｂＢ－２表达产物可能成为估价ＭＰＡ预后的可靠指标之一。     

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。     

p^53,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 …

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 正常涎腺组织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。粘液表皮样癌组织中ｐ５３、ＣｅｒｂＢ－２阳性率分别为４０．６％及４６．９％。ｐ     

癌基因c-myc抑癌基因p53在涎腺肿瘤中的表达

方法：本文采用免疫组化（ＳＰ）法，研究了３０例涎腺肿瘤。目的：观察ｃ－ｍｙｃ癌基因和ｐ５３抑癌基因在涎腺肿瘤中的表达。结果：多形性腺瘤中，ｃ－ｍｙｃ和ｐ５３阳性率分别为５０．０％和２５．０％，均分别低于恶性肿瘤的阳性率７５％和５０．８％，两组比较均有高度显著性差异（Ｐ＜０．０１）。结论：ｃ－ｍｙｃ抑癌基因ｐ５３表达与涎腺上皮细胞增殖速度加快和突变有关，ｐ５３阳性率升高，虽与细胞恶变关系密切，但仅为判断细胞分化程度的一个参考指标。     

涎腺良恶性多形性腺瘤中癌基因C—myc表达的斑点杂交研究

目的 探讨癌基因Ｃ－ｍｙｃ的改变与良恶性多形性腺瘤发生的关系。方法 采用斑点杂交研究４２例涎腺良恶性多形性腺瘤中Ｃ－ｍｙｃ癌基因的表达。结果 涎腺多形性腺瘤中Ｃ－ｍｙｃ癌基因表达均值高于正常腮腺组织（Ｐ〈０．０５）。结论 在涎腺良恶性多形性腺瘤的发生过程中,Ｃ－ｍｙｃ癌基因有激活和过量表达。     

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，     

Demonstration of c-erbB-2 oncogene overexpression in salivary gland neoplasms by in situ hybridization

The level of c-erbB-2 cellular mRNA in 18 salivary gland tumours and in 7 normal salivary glands was determined by in situ hybridization using [³⁵S] labelled RNA probes. Computer assisted quantitation of the autoradiographic signal indicated a significantly higher c- erb B-2 expression in the tumour group (22.64 grains per cell ±3.79; 95% CI) as compared to the non-neoplastic salivary gland tissue (4.11 ±0.90; 95% CI). The c-erbB-2 expression as measured by grain counts per cell for the pleomorphic adenomas (16.29± 1.87; 95% CI), mucoepidermoid carcinomas (31.52 ±0.08; 95% CI) and the acinic cell carcinomas (44.24± 17.11; 95% CI) were significantly greater than the expression for the normal group. The acinic cell carcinomas exhibited the greatest level of expression. As observed at the individual cell level, the autoradiographic signal was distributed uniformly in the neoplastic tissues, regardless of the cell type. This study confirms the hypothesis that the c-erb B-2 oncogene is overexpressed at the mRNA level in salivary gland tumours.     

Rare expression of the c-erbB-2 oncoprotein in salivary gland tumors: an immunohistochemical study

An immunohistochemical study of c-erbB-2 oncoprotein expression was carried out on 201 cases of primary salivary gland tumors, using a polyclonal antibody, raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. An intense membrane reactivity was observed in one case of sialocarcinoma transformed from pleomorphic adenoma (n = 8) and one case of mucoepidermoid carcinoma (n = 22). A comparative histopathologic evaluation of c-erbB-2 positive tumors showed marked variation in cell size, nuclear pleomorphism, multinucleation, a high mitotic rate and increased lymphoid cell infiltration and an aggressive clinical course with poor survival. The results indicate that c-erbB-2 oncoprotein is rarely expressed in malignant salivary gland tumors. However, the overexpression appears to have a distinct histopathologic feature, but a larger study incorporating histopathology and clinical data would be necessary to correlate the significance of c-erbB-2 oncogene product in salivary malignant tumors.     

涎腺肿瘤C-erbB-2癌基因mRNA表达的研究

目的 探讨Ｃ－ｅｒｂＢ２－ｍＲＮＡ表达水平同涎腺肿瘤组织类型、发生和生物学性质的关系。方法 采用ｄｏｔ ｂｌｏｔ杂交,以＾３２Ｐ标记的寡核苷酸探针,以正常涎腺为对照,对涎腺肿瘤Ｃ－ｅｒｂＢ－２ｍＲＮＡ表达进行研究。结果 正常涎腺和涎腺肿瘤中惺峭同程度Ｃ－ｅｒｂＢ－２ｍＲＮＡ的表达,以正常涎腺组织的表达水平为基准,在腺淋巴瘤、基底细胞腺瘤呈现低表达、无表达或正常涎腺组织表达水平相似,多形性腺瘤、粘液     

Genetic analysis of DNA microsatellite loci in salivary gland tumours: comparison with immunohistochemical detection of hMSH2 and p53 proteins

To investigate genetic alterations in salivary gland tumours, microsatellite instability at eight representative loci and loss of heterozygosity (LOH) on chromosome 17 were analysed by polymerase chain reaction amplification. The results were compared with immunohistochemical expression of the hMSH2 and p53 proteins. Microsatellite instability and expression loss of hMSH2 protein were not recognized in the salivary gland tumours, suggesting a low frequency of abnormalities of the mismatch repair system. LOH associated with the p53 gene was detected in approximately one-half of pleomorphic adenomas and salivary carcinomas, which often showed strong p53 immunoreactivity. These features suggest that the p53 gene plays an important role in malignant transformation of salivary gland tumours. The genetic characteristics of pleomorphic adenomas might reflect a low-grade potential for malignant progression.     

rasP21与P53在涎腺多形性腺瘤中表达的定量研究

为探讨涎腺良、恶性多形性腺瘤中ｒａｓＰ２１与Ｐ５３癌基因在该瘤生物学行为中的作用，作者采用流式细胞术和细胞免疫荧光染色技术，对ｒａｓＰ２１与Ｐ５３基因蛋白的表达量进行定量研究。结果发现，在良恶性多形性腺瘤中，ｒａｓＰ２１表达率分别为７８％和１００％；Ｐ５３表达率分别为８１％和１００％。正常腮腺组织不表达ｒａｓＰ２１与Ｐ５３。各组表达量之间差异有极显著性（Ｐ＜０．００１）。实验结果表明，ｒａｓ癌基因的激活与Ｐ５３基因突变可能在多形性腺瘤的发生及恶变过程中具有重要作用。     

涎腺肿瘤与癌基因c-myc抑癌基因p53和人类乳头状病毒感染的关系

本实验采用免疫组化、PCR技术和核酸电泳方法,对涎腺多形性腺瘤和其它类型良恶性肿瘤进行对比研究,结果显示:在涎腺多形性腺瘤中,c-myc和p53阳性率分别为50％(10/20)和25％(5/20,均远低于涎腺恶性肿瘤阳性率100％(3/3),提示c-myc表达与涎腺上皮细胞增殖速度加快有关,其表达率升高,与细胞癌变有密切联系。p53阳性表达率,虽在恶性肿瘤较高,但仅为判断细胞分化程度的一个参考指标。关于腮腺肿瘤与HPV关系,15例多形性腺瘤和3例腮腺癌中,HPV6.11均为阴性,HPV16.18阳性反应各为1例(1/5和1/3),远远低于HPV16.18在口腔肿瘤中的感染率,考虑到腮腺与口腔组织所处环境差异(后者易受烟草刺激),HPV16.18的致癌作用,主要表现为协同关系。     

Gli2基因在涎腺多形性腺瘤中的表达及其意义

目的:探讨Gli2基因在涎腺多形性腺瘤和正常涎腺组织中的表达水平及其在多形性腺瘤发生发展中的作用。方法:收集20例腮腺多形性腺瘤组织和20例相对应的瘤旁正常腮腺组织,应用逆转录聚合酶链反应(RT-PCR)和实时荧光定量PCR(Real-time PCR)方法检测Gli2基因mRNA的表达水平,分析其表达变化,并探讨Gli2基因在涎腺多形性腺瘤发生发展中的作用及其临床应用价值。结果:与正常腮腺组织相比,多形性腺瘤组织中Gli2基因mRNA的表达水平升高。结论:多形性腺瘤中Gli2 mRNA的高表达可诱导肿瘤细胞持续增殖,提示Gli2基因可能在涎腺多形性腺瘤的发生发展中具有重要作用。     

PCNA, Ki-67 and p53 expressions in submandibular salivary gland tumours

Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepidermoid carcinoma and adenoid cystic carcinoma predominate among the malignancies. Most salivary gland tumours occur in the parotid, and consequently clinical and biological data are normally derived from this site. This work describes the expressions of PCNA, Ki-67 and p53 in 15 pleomorphic adenomas, 15 mucoepidermoid carcinomas and 15 adenoid cystic carcinomas of the submandibular gland. Our results showed that all pleomorphic adenomas were negative for p53 and Ki-67 with 66.6% being positive for PCNA. Conversely, p53 was positive in 53% of the mucoepidermoid carcinomas and in 20% of the adenoid cystic carcinomas. Ki-67 was expressed in 47.7% of the mucoepidermoid carcinomas and 40% of the adenoid cystic carcinomas. All malignant tumours were positive for PCNA. These results indicate that the proliferative rate analysed with PCNA and Ki-67 and the expression of p53 in pleomorphic adenoma and adenoid cystic carcinoma of the submandibular gland were similar to those described in the parotid and minor salivary glands. However, mucoepidermoid carcinomas showed higher expression of these markers than those of other salivary glands. This work is the first describing the expression of these immunohistochemical markers exclusively in submandibular salivary gland tumours.     

Simultaneous palatal pleomorphic adenoma and mandibular keratocystic odontogenic tumor in a pediatric patient

BACKGROUND: Neoplasms of the salivary gland account for 3% of all head and neck tumors; most of these occur in the parotid gland and are benign; 80% of them are pleomorphic adenomas. Benign neoplasms of the salivary gland are rare in children compared with adults. Keratocystic odontogenic tumor (KCOT) is considered the second most frequent neoplasm of all odontogenic tumors after the ameloblastoma. In the present report, we introduce the unusual presentation of a child with a simultaneous pleomorphic adenoma of the right hard palate and a KCOT of the left mandibular angle. DISCUSSION: The case is significant for 2 reasons; according to the literature, there are few reports of pleomorphic adenoma arising from a minor salivary gland of the palate in a patient younger than 18 years. This is to our knowledge the first recorded instance of simultaneous palatal pleomorphic adenoma and mandibular KCOT occurring in a child.