口腔鳞癌中p16与p53基因表达的研究

目的　探讨口腔鳞癌中p16与p5 3基因表达特征和临床病理意义。 方法　对 31例口腔鳞癌组织采用免疫组化方法检测P16及P5 3蛋白表达。结果　 31例口腔鳞癌中P16蛋白阳性表达 17例 ,阳性率 5 4 .8% ,P5 3阳性表达 16例 ,阳性率 5 1.6 %。P16在鳞癌Ⅰ级中阳性表达 14例 (6 3.6 % ) ,Ⅱ级中阳性 1例 (33.3% ) ,Ⅲ～Ⅳ级中阳性 2例 (33.3% )。P5 3在鳞癌Ⅰ级病例中阳性 10例 (4 5 .5 % ) ,Ⅱ级中 1例 (33.3% ) ,Ⅲ～Ⅳ级中 15例 (83.3% )。P16蛋白阳性表达率随病理恶性程度增高而降低 ,但无统计学意义。结论　P5 3蛋白阳性表达率随病理恶性程度升高而增高 ,提示p5 3基因与口腔鳞癌细胞分化有相关性     

口腔鳞状细胞癌p53基因的免疫组织化学研究

随着肿瘤分子生物学研究的不断深入和发展，癌基因和抗癌基因在肿瘤发生和发展中的作用日益受到重视。Ｐ５３抗癌基因的产物是分子量为５３ＫＤ的核磷酸化蛋白质。已证明发生于１３２～２１５位氨基酸残基之间的突变可导致Ｐ５３蛋白失活，并表现出显性的癌基因转化作用［...     

口腔鳞癌发生中P53基因突变的聚合酶链反应－单链构象多态分析

建立了具有应用价值的银染ＰＣＲ－单链构象多态分析方法（ＰＣＲ－ＳＳＣＰ），应用此法对从正常口腔粘膜至口腔粘膜转移性鳞癌的各阶段组织中Ｐ５３基因５～８号外显子进行了分析。结果表明，５３％的口腔粘膜癌前损害和６５％的口腔粘膜鳞癌组织中存在ＳＳＣＰ异常带型，淋巴结转移性鳞癌组较无淋巴结转移性鳞癌组异常率更高。本研究结果提示，Ｐ５３基因在口腔粘膜鳞癌发生、发展及淋巴结转移过程中可能具有一定作用     

P53基因突变与口腔鳞癌关系的研究

本文采用多聚酶链反应技术及单链构象多态分析（ＰＣＲ／ＳＳＣＰ）检测了３４例口腔鳞癌及２０例癌旁组织中Ｐ５３基因Ⅴ、Ⅷ外显子，发现癌组织中２０例出现基因突变，阳性率为５８．８％，而在癌旁组织中无１例出现突变，本研究表明，口腔鳞癌的产生与Ｐ５３突变有关。     

p53与eIF4E在口腔鳞癌癌周组织中的表达及意义

目的用免疫组化的方法观察p53与e IF4E在口腔鳞癌癌周组织中的表达,结合癌周组织的HE染色组织病理检查,为口腔鳞癌临床手术安全切缘的确定提供理论依据。方法将口腔鳞癌癌灶中心、癌周0⁰.5 cm、0.50.5 cm、0.5¹.0 cm、1.01.0 cm、1.0¹.5 cm、1.51.5 cm、1.5².0 cm组织标本分别设为T、P1、P2、P3、P4组。正常口腔黏膜标本设为N组。将各组标本进行HE染色常规组织病理检查,同时采用免疫组化方法对标本中e IF4E与p53的表达进行检测。结果 (1)常规HE病理检查显示:口腔鳞癌癌周黏膜上皮从异常增生逐步过渡到正常黏膜形态。P1组中浸润率为42%(21/50),P2组中浸润率为16%(6/50),P3、P4组未见黏膜下癌细胞浸润。(2)p53的阳性表达率在P1、P2、P3、P4组中呈递减趋势。P1、P2组与T组表达无显著性差异(P>0.05),P4组中p53阳性表达率与N组无统计学差异(P>0.05)。(3)e IF4E在P1、P2、P3、P4组中呈递减趋势,而在P4组中阳性表达率仍然有30%,与N组差异显著(P<0.05)。结论口腔鳞癌癌周组织1.5 cm以外无癌细胞浸润,组织形态上可视为正常黏膜。p53、e IF4E在口腔鳞癌及癌周组织中有趋势性的差异表达,p53的分子边界为肉眼边界外1.5 cm,e IF4E边界则在2.0 cm以外,e IF4E过表达在口腔鳞癌的发生过程中可能是比p53异常更为早期的分子事件,临床手术中有条件时要尽量将口腔鳞癌的手术边界扩大到癌周2.0 cm以外,如无法达到则要保证1.5 cm的边界,通过术后综合治疗防止肿瘤复发。     

口腔鳞癌中HPV感染状况与抑癌基因P53突变关系的研究

采用多聚酶链反应技术扩增３０例福尔马林固定石蜡包埋的口腔鳞癌组织中的ＨＰＶ ＤＮＡ及Ｐ５３第七外显子基因，结果显示ＨＰＶ ＤＮＡ阳性者２２例，Ｐ５３基因有突变者１６例。其中ＨＰＶ ＤＮＡ阳性者约有１／２存在着Ｐ５３基因突变，ＨＰＶ ＤＮＡ阴性者绝大部分在Ｐ５３突变。本研究表明Ｐ５３基因突变在ＨＰＶ ＤＮＡ阴性的鳞癌的癌发生中发挥了重要作用，而在ＨＰＶ ＤＮＡ阳性的鳞癌中Ｐ５３基因突变只是鳞癌发生中     

新疆维吾尔族、汉族口腔黏膜癌前病变及口腔鳞状上皮细胞癌P53蛋白、PCNA的表达

目的 探讨新疆维吾尔族、汉族口腔黏膜癌前病变及口腔鳞状细胞癌的发生与发展过程中, P53蛋白和PCNA的表达及意义。方法 应用免疫组织化学方法对40例口腔扁平苔藓(维吾尔族20例, 汉族20例), 43例口腔白斑(维吾尔族23例, 汉族20例), 65例口腔鳞状细胞癌(维吾尔族24例, 汉族41例)分别进行检测。结果 ① 口腔鳞状细胞癌组织中突变型P53蛋白阳性率为47.7%, 明显高于口腔白斑(11.6%)和口腔扁平苔藓(0)(P＜0.005), 维族与汉族之间的差异均无统计学意义(P＞0.05)。② PCNA的阳性率在口腔鳞状细胞癌组织中为81.5%, 明显高于口腔白斑(16.3%)和口腔扁平苔藓(0)(P＜0.005), 维族与汉族之间无明显差异(P＞0.05)。结论 ① P53基因突变使P53蛋白过表达和PCNA的过表达在口腔磷状上皮细胞癌的发生与发展过程中起着十分重要的作用。② 据本研究资料, 尚不能认为以上各指标中维族与汉族之间有显著性差异。     

野生型p53基因对口腔鳞状细胞癌细胞系生长的影响

目的 :研究 p5 3基因对口腔鳞状细胞癌细胞系生长的影响。 方法 :以人鳞状细胞癌细胞系Tca83和Tca8113为实验对象 ,将载有人野生型p5 3cDNA的重组腺病毒 (Ad5CMV -p5 3 )感染鳞状细胞癌细胞系 ,观察Ad5CMV -p5 3对鳞状细胞癌细胞生长的影响。 结果 :鳞状细胞癌细胞系Tca83和Tca8113被转染Ad5CMV -p5 3病毒后 ,均可以诱导其发生调亡 ,使细胞系生长受到明显的抑制。结论 :Ad5CMV -p5 3介导的野生型p5 3基因治疗口腔鳞状细胞癌可能是一种有效的辅助手段     

Tca8113细胞株电穿孔法p53基因转染及G418体外筛选条件的研究

通过体外细胞培养方法，研究了进行舌鳞癌细胞株Ｔｃａ８１１３ｐ５３基因电穿孔法转染的最佳实验条件。结果显示在细胞培养至３６ｈ、电场强度为６２５Ｖ／ｃｍ时转染效果最佳，转染后选择剂Ｇ４１８的最佳浓度为３００μｇ／ｍｌ。按此条件已成功地进行了ｐ５３基因的体外转染。     

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。     

p53 expression in oral precancer and cancer

Expression of the p53 tumour suppressor gene is a frequent finding in human malignancies, including oral cancer, and it has been detected in some potentially malignant lesions. The results of the present project showed that 35 of the 41 (85 per cent) oral mucosal lesions with histological evidence of epithelial dysplasia expressed p53, but the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.     

Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma

OBJECTIVE: To assess p53 expression in a range of oral mucosal lesions and to relate the results to the clinical outcome in patients with dysplastic oral mucosal lesions and oral squamous cell carcinomas (OSCC).
MATERIALS AND METHODS: Archival tissue was available for eight cases of normal oral mucosa, 50 cases of oral mucosal hyperplasia, 41 cases of oral mucosal dysplasia and 48 cases of OSCC. The monoclonal antibody DO-7, reactive to p53 protein, was applied to paraffin-embedded sections using microwave pretreatment and immu-nohistochemical techniques.
RESULTS: The results showed that normal oral mucosa did not express p53.Positive nuclear staining was found in 18/50 (36%) cases of hyperplasia, 35/41 (85%) cases of dysplasia and 45/48 (94%) cases of OSCC.None of the p53 negative dysplasias progressed, while 19% of p53 positive cases of dysplasia recurred following excision and 11% of the cases underwent neoplastic transformation. Five out of 10 (50%) cases of severe dysplasia which were p53 positive resolved.
CONCLUSION: The proportion of cases with positive p53 expression increased from hyperplasia to dysplasia to OSCC. These results may indicate an involvement of p53 in neoplastic transformation as well as in proliferative events although the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.     

High Frequency of p53 Gene Mutations in Oral Squamous Cell Carcinoma

目的 :研究口腔鳞状细胞癌发生发展过程中p5 3抑癌基因 5 - 8外显子的突变。方法 :采用非同位素PCR -SSCP -EB染色技术。结果 :30例口腔鳞癌组织标本中 ,16例检测出p5 3基因点突变。结论 :口腔鳞癌中p5 3基因点突变率为 5 3.3% ,p5 3基因突变与口腔鳞癌的发生发展关系密切     

Expression form of p53 and PCNA at the invasive front in oral squamous cell carcinoma: correlation with clinicopathological features and prognosis

J Oral Pathol Med (2011) 40 : 693–698 Background: Abnormalities in cell‐cycle‐controlling genes are important in the malignant transformation and proliferation of tumors. Among these genes, the tumor suppressor gene p53 is the most notable, and its mutations provide an indicator of tumor progression and prognosis. Proliferating cell nuclear antigen (PCNA) is a highly conserved nuclear protein that is expressed during cell replication and DNA repair. This study examined the expression of p53 and PCNA at the invasive front of oral squamous cell carcinomas (OSCC) by immunohistochemical staining, and investigated the relationship of these proteins to clinicopathological findings and prognosis. Methods: Fifty‐nine biopsy cases of OSCC were examined by immunohistochemical staining. Clinicopathological data were gathered and patient survival was analyzed. Results: The p53 labeling index (p53‐LI) and PCNA labeling index (PCNA‐LI) were examined at the invasive front of the tumors. A high p53‐LI (p53+) was observed in 17 of the 59 cases (28.8%) and a high PCNA‐LI (PCNA+) was observed in 28 of the 59 cases (47.5%). Among the modes of cancer invasion, many of the p53+/PCNA+ cases could be confirmed as highly invasive cancer (P < 0.05). In addition, the p53+/PCNA+ cases showed a high risk of tumor recurrence compared with the other expression forms, and patients with p53+/PCNA+ had a worse prognosis than those with the other expression forms. High labeling indices of p53 and PCNA are associated with poor prognosis in patients with OSCC. Conclusion: We suggest that it is important to investigate the expression of p53 and PCNA at the invasive front of OSCC.     

p53, PCNA and Ki-67 expression in oral squamous cell carcinomas: the vagaries of fixation and microwave enhancement of immunocytochemistry

Proliferation markers are widely used as indicators of tumour progression and aggression. Fixation and antigen retrieval methods may enhance the immunocytochemical sensitivity of these markers but may also lead to loss of specificity. As these methods are often used quantitatively, standardisation of internal and external methodology is paramount. This study aimed to compare the effects of alcohol and formalin fixation and of microwaving on the immunocytochemical demonstration of p53, PCNA and Ki-67 in oral squamous cell carcinoma using duplicate tissue blocks from 24 cases. Both qualitative and quantitative differences in antigen expression were revealed. Whilst alcohol fixation alone at least maintained and usually increased the strength of positive staining, microwaving alcohol-fixed sections often gave rise to non-specific staining. p53 staining following microwave enhancement of alcohol-fixed tissue showed a significant incidence of conversion of negative results to positive and of positive staining in unexpected tissue components. Alcohol fixation increased the sensitivity of PCNA detection with a far less dramatic loss of specificity. The results emphasise the need for careful standardisation of immunocytochemical methods, particularly when used quantitatively and for inter-laboratory comparisons.     

Prognostic impact of p53 and p63 immunoexpression in oral squamous cell carcinoma

BACKGROUND: The role of p53 and p63 proteins in the prognosis of oral squamous cell carcinoma (OSCC) is still debatable. Our aim here was to investigate the relationship between the immunoexpression of these proteins with some clinicopathologic parameters of prognostic significance in OSCC. METHODS: Formalin-fixed paraffin-embedded sections from 106 patients were used for study together with the following data: primary site, histologic differentiation, recurrences, metastasis, disease-free survival and overall survival (OS). RESULTS: In OSCCs, the positive rate for p63 protein immunoexpression (87.8%) was higher than p53 (52.8%). p53 expression correlated with metastasis. Tumors negative for p53 and with strong intensity for p63 expression had a significantly higher OS. CONCLUSIONS: p53 overexpression is associated with a larger number of metastases and is correlated with a poor outcome as well as decreased intensity in p63 immunoexpression.