舌鳞状细胞癌中p73、p63和p53基因的表达

目的：研究p73、p63和p53基因蛋白在舌鳞状细胞癌中的表达及其意义。方法：用免疫组织化学S－P法检测64例舌鳞状细胞癌组织标本p73、p63和p53基因蛋白表达。结果：舌鳞癌中p73、p63和p53基因蛋白阳性率分别为61％、92％和50％。p73蛋白表达与T分类(r=0.344,P=0.057)、区域淋巴结转移（r=0.334,p=0.007)、肿瘤侵袭方式（r=0.340,P=0.060)和不良预后（r=-0.473,P=0.000)相关。p63与所有临床病理特征和预后无关。p53与区域淋巴结转移（r=0.263,P=0.036)和不良预后（r=-0.342,P=0.013)相关。结论：p73和p53表达有助于判断舌鳞癌的生物学行为和预后。p63可能是鳞状上皮源性肿瘤的标记物。     

抑癌基因p53基因克隆和表达

目的;本研究对抑癌基因ｐ５３进行基因克隆和表达以获得ｐ５３基因产物,方法：采用基因克隆重组技术将ｐ５３ｃＤＮＡ编码区重组到融合蛋白表达载体ｐＧＥＸ－２Ｔ中,用免疫斑点杂交技术检测ｐ５３融合蛋白在大肠杆菌中的表达。结果：我们获得了ｐ５３基因融合蛋白表达质粒ｐＧＥＸ－ｐ５３并在大肠杆菌中获得了表达。结论：ｐＧＥＸ－２Ｔ是一个有效的融合基因表达载体,适合于ｐ５３基因的表达,用ｐＧＥＸ－ｐ５３可以很方便地     

舌癌P53蛋白的表达及p53基因的突变

目的:检测舌癌中P53蛋白表达和p53基因突变及其与临床病理的相关性。方法:应用免疫组织化学和聚合酶链反应—单链构象多态性分析(PCR-SSCP)检测10例舌白斑和32例舌癌,并结合临床资料进行分析。结果:PCR-SSCP检测舌白斑和舌癌p53基因突变率分别为20.0%(2/10)和59.4%(19/32)。突变的19例舌癌,12例出现第5外显子突变,7例出现第6外显子突变,2例出现第7外显子突变,15例出现第8外显子突变。其中单外显子突变10例,多外显子突变9例。免疫组化结果表明,舌白斑和舌癌P53蛋白阳性率分别为20.0%(2/10)和46.9%(15/32);P53的表达与临床分期及有无淋巴结转移密切相关。临床I、Ⅱ期病例P53蛋白表达水平低于Ⅲ、IV期病例(P<0.05)。无颈淋巴结转移病例的P53蛋白表达水平低于有转移的病例(P<0.05)。采用免疫组化和PCR-SSCP检测舌癌的符合率为75.0%(24/32)。结论:舌癌发生过程中p53基因有突变,最多发生在第8外显子,其次为第5、6外显子;P53蛋白阳性的舌癌患者多处于临床晚期,易发生淋巴结转移,且预后较差。     

非同位素PCR-SSCP-EB染色技术检测头颈部鳞癌p53基因点突变

应用非同位素ＰＣＲ－ＳＳＣＰ－ＥＢ染色技术检测新鲜头颈部鳞癌组织中ｐ５３基因点突变。结果显示１３例标本中７例有异常电泳带，其中位于第５外显子者１例，位于第６，７，８外显子者各２例，说明头颈部鳞癌的发生与ｐ５３基因突变有密切关系。与传统的同位素ＰＣＲ－ＳＳＣＰ相比，非同位素ＰＣＲ－ＳＳＣＰ－ＥＢ染色技术是一种更简便、安全、快速、有效的检测基因点突变的方法，适用于大量标本基因点突变的筛选性检测。     

涎腺腺样囊性癌p53基因蛋白的表达及其临床意义

目的 为探讨涎腺腺样囊性癌ｐ５３基因蛋白的表达及其临床意义。方法 作者应用流式细胞术及细胞免疫荧光染色技术,对涎腺腺样囊性癌ｐ５３基因蛋白的表达进行了定量研究。结果 结果表明,正常涎腺组织ｐ５３表达均为阴性,涎腺腺样囊性癌ｐ５３基因蛋白表达量及表达阳性率与该肿瘤的浸润情况密切相关,ｐ５３基因蛋白表达量与预后亦有相关性。结论 ｐ５３基因蛋白表达量及表达阳性率与腺样囊性癌组织学分型、ＤＮＡ倍体水平及细     

p16和p53蛋白在口腔白斑和鳞状细胞癌中表达的比较研究

目的比较p16和p53在口腔白斑和口腔鳞状细胞癌中异常表达的情况。方法对17例健康者的口腔粘膜、60例白斑患者和40例口腔鳞状细胞癌患者的病损组织进行了p16和p53蛋白的免疫组化染色。结果正常口腔粘膜、白斑单纯增生、白斑异常增生和口腔鳞状细胞癌的p16阳性率分别为100％、90％、60％和35％，p53蛋白的阳性率分别为12％、27％、50％和73％，p16阳性率和细胞染色强度指数（stainning intensity index，SII）分别与口腔粘膜组织恶性度的增高显著负相关；p53阳性率和S11分别与口腔粘膜组织恶性度的增高显著正相关。p16和p53在不同组织中的阳性率显著负相关；p16和p53在白斑异常增生的协同失活率达23％，在口腔鳞状细胞癌中达到42．5％。p16阳性率、p16SII、p53SII及两种基因均异常的比率在口腔鳞状细胞癌无淋巴结转移和口腔鳞状细胞癌有淋巴结转移患者之间均有显著差异。结论p16可作为早期监视口腔白斑恶变、监测口腔鳞状细胞癌发展进程和判断口腔鳞状细胞癌预后的分子生物学指标。p16和p53失活在白斑癌变和口腔鳞状细胞癌的发展过程中可能有叠加效应。     

口腔粘膜鳞癌和癌前病变p53、ras基因突变的检测及p53、p21蛋白的表达

目的　探讨 p5 3、ras基因改变在口腔粘膜鳞癌及癌前病变发生过程中的意义。方法　应用聚合酶链反应和免疫组织化学法检测 2 3例口腔粘膜鳞癌和 15例癌前病变 p5 3、ras基因突变和 p5 3、p2 1蛋白的表达。结果　43.5 % (10 / 2 3)的口腔粘膜鳞癌存在 p5 3基因第 8外显子突变 ,47.8% (11/ 2 3) ras基因有突变 ;口腔粘膜鳞癌 p5 3、p2 1蛋白表达阳性率分别为 43.5 % (10 / 2 3)和 6 0 .9% (14/ 2 3)。癌前病变有 1例存在 p5 3基因第 8外显子和 ras基因突变 (6 .7% ) ;p5 3、p2 1蛋白表达阳性率分别为 13.3% (2 / 15 )和 2 0 % (3/ 15 )。两组间差异显著 (P<0 .0 5 )。结论　 p5 3、ras基因突变和 p5 3、p2 1蛋白过量表达与口腔粘膜鳞癌的发生过程密切相关 ,可作为癌前病变发展为癌危险性的生物指标     

肿瘤抑制基因P53及其在口腔癌中的表达

肿瘤抑制基因是一种抑制细胞非正常性增生的基因,P53基因是继RB基因后新确认的一个肿瘤抑制基因,其野生型能抑制细胞的恶性转化,而突变型则与人类许多肿瘤的发生密切相关。已在口腔癌中发现突变型P53蛋白的过量表达及P53基因的突变和缺失,揭示了口腔癌癌变机理研究的新领域。本文对P53基因及其产物的一般性质、作用机理及其在口腔癌中表达的研究现状进行综述。     

p53蛋白在口腔疣状癌组织中的表达及意义

目的 :研究口腔疣状癌中p5 3蛋白的表达状况及与口腔粘膜鳞状细胞癌的表达对比 ,探讨p5 3蛋白在口腔疣状癌发生过程中的生物学意义。方法 :采用SP免疫组化方法分别检测 8例正常口腔粘膜、1 3例疣状癌、1 0例高分化鳞癌、1 0例低分化鳞癌组织中p5 3蛋白的表达。结果 :疣状癌p5 3蛋白阳性表达率为 6 9.2 % (9/ 1 3) ,高分化鳞癌组和低分化鳞癌组阳性表达率均为 80 % (8/ 1 0 ) ,而正常口腔粘膜上皮均呈阴性表达 ,疣状癌p5 3蛋白平均染色强度低于高分化鳞癌和低分化鳞癌组 ,差异有显著性 (P <0 .0 5 ) ;高分化鳞癌的平均染色强度低于低分化鳞癌组 ,差异有显著性 (P <0 .0 5 )。结论 :口腔疣状癌的发生过程中可能存在p5 3基因突变 ,疣状癌与高分化鳞癌、低分化鳞癌组织中p5 3蛋白的表达差异可作为其鉴别诊断的有用指标之一     

唾液腺腺样囊性癌p53基因突变及其与临床病理的关系

目的:研究唾液腺腺样囊性癌(ACC)p53基因突变及其与临床病理因素的关系。方法:选择38例唾液腺ACC病理标本,采用聚合酶链式反应单链构象多态性分析(PCR-SSCP)进行p53基因突变(5-8外显子)的检测;应用SPSS10.0统计学分析软件,采用Kaplan-Meier法进行生存分析,并绘制生存曲线。p53基因突变与ACC各病理类型、局部复发率、远处转移率及临床分期的关系采用Fisher精确检验。结果:p53基因5-8外显子突变检出率为65.8%,p53基因突变与唾液腺ACC的肿瘤复发、远处转移及术后生存有关(P<0.05),与肿瘤病理类型、临床分期无关(P>0.05)。结论:p53基因突变在唾液腺ACC中有较高的检出率,并可能与患者的预后有关。     

The changing face of p53 in head and neck cancer

p53 plays a sentinel role in the pathways that prevent development of cancer by inducing apoptosis, DNA repair and cell-cycle arrest in response to different types of cellular stress. The majority of head and neck tumours harbour mutations affecting the p53 gene, and those tumours that seemingly have wild-type p53 protein most probably lack a functional p53 response as a result of mutations affecting other genes that function in the same pathways as p53. This report provides an up-to-date overview of what is known about how p53 exerts its effects. We also summarize what is known about the other p53 family members, p63 and p73, and show how they act together to influence the response to treatment. No other commonly occurring signature mutation has emerged for this tumour type, and this means that the p53 family has emerged as the frontrunner in terms of providing molecular targets that can provide new diagnostic, prognostic and therapeutic approaches.     

p53 overexpression in head and neck squamous cell carcinoma: Review of the literature

As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human cancers. Mutations of p53 have been implicated in the pathogenesis of head and neck squamous cell carcinoma (HN-SCC) at a high incidence. In premalignant lesions and in situ carcinomas, p53 overexpression is not exclusively restricted to neoplastic cells, but frequently affects the normal appearing keratinocytes adjacent to p53 positive neoplasms or present in dysplastic areas. These results suggest that as contributors to the early phases of HN-SCC development, p53 alterations may be excellent biomarkers that indicate the predisposition of a particular oral cavity premalignant lesion toward malignancy. In most cases, the p53 overexpression status of a tumour metastasis is identical to that of a primary tumour, indicating that a p53 mutation precedes metastatic spread. In patients with multiple primary tumours, multiple foci of p53 overexpression are observed in epithelia distant from the tumour. So the expression of p53 in normal epithelium would indicate an increased risk for transformation to second or third primary cancers. Distinct p53 mutations in different primary tumours of the same patient indicate that these cancers arise as independent events; these results support the existence of multifocal polyclonal processes. Regardless of the aforementioned results that support p53 as a valid tumour biomarker, most studies have shown no relationship between the expression of p53 and clinical and histopathological parameters. The role played by p53 mutations in the progression and vital prognosis of HN-SCC has not yet been demonstrated.     

p53, bcl-2 and bax abnormalities in non-Hodgkin's lymphomas of the head and neck

In the present study, mutations or protein expression of p53, bcl-2 and bax are reported in 13 non-Hodgkin's B-cell lymphomas of the head and neck. Nine of 13 cases (69.2%) expressed p53 protein and 7 (53.8%) showed gene mutations. On comparing the results of immunostaining and SSCP analysis, there were two cases showing discrepancies between the p53 protein expression and gene mutations. Bcl-2 protein expression was observed in only two cases of follicular lymphoma. On the other hand, bax protein was detected in all 13 cases. One case with mutated bax gene showed a lower expression with a reduced frequency of bax-positive cells than the other 12. These results suggest that inactivation of p53 may be closely related to development and/or progression of these NHLs, and that bcl-2 and bax protein may not have a role.     

The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent studies have focused on the TP53 tumour suppressor gene, analysing its gene status and protein status. When looking at p53 protein expression, using immunohistochemistry, no correlation to patient outcome has been seen for the whole group of SCCHN. However, a significant association between p53 expression and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning the prognostic significance of mutations in the TP53 gene, results differ. But when restricting analysis to tumours with mutations causing an obvious change in protein, TP53 mutation was found to be a strong and independent variable for prognosticating survival. This review article gives an up-to-date overview of the p53 molecule and evaluates its possible prognostic role in SCCHN. Today it is clear that the p53 pathway is very important in SCCHN biology and potentially in its treatment. The function and importance of a few other cell cycle proteins connected to p53 are also discussed.