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.     

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。     

Flow cytometric S-phase fraction contributes to diagnosis of diploid malignant salivary gland tumours

DNA ploidy studies on salivary gland tumours have shown that the proportion of aneuploid cases, although confined to the malignant entities, is considerably lower than for other solid malignancies. To analyse whether the S-phase fraction (SPF) may contribute to discrimination of diploid malignant from benign tumours, DNA flow cytometric data from 45 different malignant salivary gland tumours was compared with that of 121 pleomorphic adenomas. All benign tumours were diploid. Twelve malignant tumours contained aneuploid cell populations. The SPF values for diploid malignancies ranged between 0.9% and 11.0% (mean 3.9%), and between 0.5% and 7.9% (mean 2.7%) for pleomorphic adenomas. A 4% cut-off value gained statistical significance for discriminating diploid malignant tumours from pleomorphic adenomas (P<0.01). The sensitivity for SPF>4% was 46% and the positive predictive value was 40%. A sensitivity of 60% and a positive predictive value of 54% was achieved by combining aneuploidy and SPF>4%. These results show that DNA flow cytometry may contribute to diagnostic assessment in salivary gland tumours.     

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。     

P53 and Ki-67 antigen expression in small oral biopsy specimens of salivary gland tumors

OBJECTIVE: To investigate the possibility that various salivary gland tumors that look histologically similar could express p53 oncoprotein and Ki-67 proliferation antigen differentially and possibly aid in distinguishing benign from malignant lesions.Study Design: Intraoral paraffin-embedded biopsy specimens of salivary gland tumors were used. Thirty-eight pleomorphic adenomas, 17 adenoid cystic carcinomas, 23 monomorphic adenomas, and 17 polymorphous low-grade adenocarcinomas were stained with p53 and Ki-67 antibodies by using an immunoperoxidase detection system. Each case was evaluated in terms of staining intensity and percentage of cells staining. RESULTS: Ki-67 and p53 antigens are expressed in generally low levels in the histologically well-differentiated salivary tumors that were studied here, both benign and malignant. Only 1 solid-type adenoid cystic carcinoma showed a high percentage of cells expressing p53. CONCLUSIONS: The histologically well-differentiated salivary tumors studied do not show differential expression of p53 and Ki-67, in spite of their differing courses of biologic behavior. These antibodies should not be relied on to distinguish benign from malignant lesions of the salivary glands; however, they might be markers for those lesions that are dedifferentiating histologically and, therefore, might be displaying more aggressive behavior.     

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．     

Tumours of the minor (oropharyngeal) salivary glands: a demographic study of 336 cases

There arc 2410 primary epithelial salivary gland tumours in the files of the British Salivary Gland Tumour Panel. Of these tumours, 336 (14%) involved the minor (oropharyngeal) salivary glands, and these were studied m the present investigation Individual tumours were diagnosed according to the W H O Classification The percentage of malignant or potentially malignant tumours (46%) was much higher than in major glands (18%), and in some of the less common intraoral sites all the tumours were malignant. The principal sites were the palate (54%), lips (21%) and buccal mucosa (11%), and, in these sites, pleomorphic adenoma was the most common tumour Monomorphic adenomas accounted for 6% of palatal tumours, hut 30% of lip salivary gland tumours. The most common malignant tumour was the adenoid cystic carcinoma The results arc compared with several other large surveys and with tumours of major salivary glands.     

Expression and mutations of p53 in salivary gland tumours

A series of 219 salivary gland tumours (103 carcinomas and 116 benign tumours) were analysed for p53 protein expression using immunohistochemistry, and for mutations in p53 gene using non-radioactive single strand conformation polymorphism (SSCP). p53 expression was present in 36% (42/116) of the benign tumours and in 54% (56/103) of the carcinomas. The highest prevalence of p53 expression was found in adenoid cystic carcinomas (69%). followed by mucoepidermoid carcinomas (67%). Of the benign tumours, pleomorphic adenomas showed the highest prevalence of p53 positivity (41%). In malignant tumours, expression of p53 bore no correlation to local recurrence, metastatic disease or survival of the patients. Exons 5 through 9 were analysed and four mutations were found in 20 cases of p53-immunopositive tumours and two in 20 p53-negative tumours. Each of the exons 5.6 and 8/9 had two mutations, whereas no mutations were detected in exon 7.     

Maintaining a high level of suspicion for recurrent malignant disease: report of a case with periapical involvement

Aim: To report the unusual endodontic presentation and radiographic features of a subgroup of pleomorphic adenoma called carcinoma ex pleomorphic adenoma and to stress the importance of maintaining a high level of suspicion in cases where primary or recurrent neoplasia is included in the differential diagnosis. SUMMARY: This paper describes a case in which a patient with a previous history of malignant neoplasm presented with signs and symptoms similar to a dental infection. The pathology report however confirmed recurrence of the previous tumour in a malignant fashion. The importance of maintaining a high level of suspicion in early management of such disease is highlighted. KEY LEARNING POINTS: *Pleomorphic adenomas, also known as benign mixed tumours, are common salivary gland tumours, which infrequently undergo malignant transformation, with potentially devastating consequences. *Malignant salivary gland tumours can present as dental swelling, dental pain and sudden loss of vitality of teeth so both general practitioners and specialists have the responsibility to evaluate such patients with a broad vision. *Radiographic differential diagnosis of periapical radiolucency should also include malignant salivary gland tumours. *This case highlights the need of vigilance at all times and emphasizes the benefits of biopsy and histological examination in the diagnosis of recurrent malignant salivary gland tumours.     

Quantitative study on nucleolar organizer regions in salivary gland tumours]

The argyrophil staining technique for nucleolar organizer regions (NOR) had been applied to a series of benign and malignant salivary gland tumours. We have studied 38 salivary gland tumours, 16 benign and 22 malignant. In all specimens clearly defined silver-stained intranuclear AgNOR dots were visible. The differences between the numbers of AgNORs in the benign and malignant groups, notably pleomorphic adenomas, adenoid cystic carcinoma, mucoepidermoid carcinoma and adenocarcinoma, were highly significant. This result suggested that the AgNOR technique is of diagnostic help in distinguishing between these salivary gland tumours.     

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。     

1878例涎腺肿瘤WHO组织病理学新分类的统计分析

目的 根据ＷＨＯ１９９０年涎腺肿瘤组织病理学新分类标准对１８７８例涎腺肿瘤及肿瘤样疾病进行重新分类,并重点对涎腺上皮性肿瘤的临床发病情况进行统计分析。方法 统计描述。结果 １８７８例涎腺肿瘤以诞腺上皮性肿瘤为主,为１４３１例,占７６．２０％,其中腺瘤发病居首位,其次是涎腺癌,涎腺肿瘤样疾病居第三位;多形性腺瘤是涎腺肿瘤中最常见者,恶性多形性腺瘤为最常见的涎腺癌,特别注意了腺癌亚分类中的几种少见类型     

Expression of hMSH2 and hMLH1 proteins of the human DNA mismatch repair system in salivary gland tumors

BACKGROUND: The human DNA mismatch repair (hMMR) system plays an important role in reducing mutation and maintaining genomic stability. The MMR system in human cells is composed of at least six genes (hMSH2, hMLH1, hMSH3, hPMS1, hPMS2 and GTBP/hMSH6). In particular, hMSH2 and hMLH1 are expressed in cells undergoing rapid renewal; their reduced expression has been reported in several tumors. METHODS: We examined the expression of hMSH2 and hMLH1 by immunohistochemistry in tumor specimens from 43 patients with primary tumors. RESULTS: All carcinomas (n = 20) expressed these proteins. In addition, when compared to pleomorphic adenomas, malignant tumors contained significantly (P < 0.01) higher proportions of hMSH2 (56.1 +/- 31.5 vs. 31.1 +/- 22.6) and hMLH1 (27.9 +/- 26.0 vs. 14.0 +/- 12.6) positive cells. Warthin's tumors showed no specific nuclear staining of tumor cells for both hMSH2 and hMLH1. CONCLUSIONS: These data suggest a minor, if any, role for a defect in the hMMR system in the pathogenesis of malignant salivary gland tumors.     

Tumours of the minor (oropharyngeal) salivary glands: a demographic study of 336 cases

There are 2410 primary epithelial salivary gland tumours in the files of the British Salivary Gland Tumour Panel. Of these tumours, 336 (14%) involved the minor (oropharyngeal) salivary glands, and these were studied in the present investigation. Individual tumours were diagnosed according to the WHO Classification. The percentage of malignant or potentially malignant tumours (46%) was much higher than in major glands (18%), and in some of the less common intraoral sites all the tumours were malignant. The principal sites were the palate (54%), lips (21%) and buccal mucosa (11%), and, in these sites, pleomorphic adenoma was the most common tumour. Monomorphic adenomas accounted for 6% of palatal tumours, but 30% of lip salivary gland tumours. The most common malignant tumour was the adenoid cystic carcinoma. The results are compared with several other large surveys and with tumours of major salivary glands.     

DNA-Ploidie und proliferative Aktivität bei Speicheldrüsentumoren

DNA ploidy and S-Phase fraction (SPF) of 279 salivary gland tumours were analysed using high-resolution DNA flow cytometry. All 229 benign neoplasms were diploid while 12 of 50 malignant tumours showed cell populations with aneuploid DNA content. The SPF values of diploid malignancies were significantly higher if compared with pleomorphic adenomas but did not differ from that of the zystadenolymphoma (Warthin tumour) group. While aneuploidy represents a distinct indicator of malignancy SPF values are of minor relevance for dignity assessment in salivary gland tumours.     

Multiple pleomorphic adenomas arising in the parotid and submandibular lymph nodes

We report rare case of multiple pleomorphic adenomas arising in the parotid and submandibular lymph nodes of a 21-year-old man. These tumours were surrounded by lymphoid tissue which was almost identical to that of the cortex of lymph node. The possibility of metastasizing pleomorphic adenomas was discounted because the mitotic activity was low and there were no signs of infiltration. Heterotopic salivary gland tissue was also found in the lymph nodes that contained the tumours, and each tumour expressed a similar immunohistochemical staining pattern to that of the salivary gland tissue. These findings indicate that these pleomorphic adenomas probably arose from the salivary gland tissue within the lymph nodes.     

2489例涎腺上皮性肿瘤临床病理分析

目的:了解涎腺上皮性肿瘤的临床病理特点。方法:对2489例涎腺上皮性肿瘤临床病理资料进行统计分析。结果:涎腺恶性上皮性肿瘤840例,腺样囊性癌、黏液表皮样癌、癌在多形性腺瘤中居其前3位;涎腺良性上皮性肿瘤1649例,多形性腺瘤、Warthin瘤、基底细胞腺瘤居其前3位。涎腺恶性、良性上皮性肿瘤男女之比为1.13∶1和0.99∶1;平均发病年龄47.86岁和44.86岁;腮腺和腭部为好发部位。结论:腺样囊性癌和多形性腺瘤是最常见的涎腺恶性、良性上皮性肿瘤。     

HSV-tk与p53基因对涎腺多形性腺瘤细胞的杀伤作用

目的　观察腺病毒介导的单纯疱疹病毒胸苷激酶(HSV-tk)基因、野生型p53基因(wt-p53)联合杀伤人涎腺 多形性腺瘤细胞的效果。方法　采用腺病毒介导的HSV-tk基因、wt-p53基因联合转染人涎腺多形性腺瘤细胞,逆 转录聚合酶链式反应(RT-PCR)检测转染后的基因表达;四唑盐比色(MTT)法测定tk与p53基因治疗后对肿瘤细 胞的杀伤作用及旁观者效应,并采用相差显微镜观察基因治疗后肿瘤细胞的形态学变化。结果　单独转染wt-p53 及HSV-tk/GCV基因5 d后,涎腺多形性腺瘤细胞的存活率分别为54%和38%;两者联合转染5 d后,细胞的存活率 降至20%,两者差异有显著性(P<0.05)。结论　HSV-tk、wt-p53基因联合应用对涎腺多形性腺瘤的杀伤作用强于 此两基因单独应用的杀伤作用。