口腔鳞癌中Rb/cyclinD1/p16通路表达及其病理意义

目的：探讨口腔鳞癌(OSCC)中Rb／cyclinD1／p16通路表达及其病理意义。方法：使用免疫组化方法在37例OSCC标本中检测Rb、cyclinD1、p16蛋白表达,并与患者临床病理参数进行相关性分析。结果：Rb、p16、cyclinD1阳性表达率分别为76％、49％和57％;Rb和p16表达呈负相关(P=0．02);cyclinD1表达与肿瘤大小(P=0．02)和淋巴结转移(P=0．01)呈正相关;p16表达与年龄呈负相关(P=0．02)。结论：1)OSCC中和Rb和p16之间可能存在的调控机制;2）p16缺失是OSCC发生中的早期事件;3)cyclinD1对肿瘤的生长作用大于对肿瘤的发生作用,与OSCC的增殖和淋巴结转移关系密切,并可能作为标志物对OSCC的预后和转移作出评估。     

p53和增殖细胞核抗原在口腔白斑和口腔鳞状细胞癌中的表达及意义

目的 检测正常口腔黏膜、口腔黏膜白斑和口腔鳞状细胞癌(OSCC)中p53和增殖细胞核抗原(PCNA)表达,探讨p53和PCNA在OSCC癌变过程中的规律及相关性.方法 口腔黏膜白斑标本20例、OSCC标本31例及正常口腔黏膜10例,采用免疫组化SP法检测其p53和PCNA的表达,应用SPSS 11.0软件包对结果进行χ2检验、单因素方差分析和线性回归分析.结果 p53在正常黏膜组、白斑组与鳞状细胞癌组的表达率分别为0%、35%和77.4%,PCNA在上述三组中表达率分别为30%、70%和96.8%,两种表达的组间比较差异有统计学意义(P<0.05);p53蛋白与PCNA表达呈正相关(P<0.01).结论 p53基因和PCNA表达水平均与OSCC发展进程密切相关.     

口腔黏膜癌前病变和口腔鳞状细胞癌中Stat3的表达及意义

目的研究口腔黏膜癌前病变和口腔鳞状细胞癌(OSCC)中细胞信号传导和转录激活因子(Stat3)的表达及意义。方法采用免疫组化方法分别检测9例正常口腔黏膜,口腔扁平苔藓(OLP)和白斑(OLK)共8例,OLP、OLK伴异常增生22例,OSCC19例中Stat3的表达。结果Stat3阳性表达分布于细胞质和细胞核内。正常口腔黏膜、单纯增生、异常增生和OSCC中Stat3阳性表达率分别为11.11%(1/9)、12.50%(1/8)、59.09%(13/22)和84.21%(16/19)。OSCC与正常口腔黏膜、单纯增生、异常增生相比,差异有显著性(P<0.05);异常增生与正常口腔黏膜、单纯增生相比,差异有显著性(P<0.05);而单纯增生和正常口腔黏膜相比差异无显著性(P>0.05)。结论Stat3与口腔黏膜癌变的发生发展有着密切关系,对Stat3表达的研究将有助于口腔黏膜癌前病变癌变的检测和OSCC的早期诊断。     

Stat3和cyclinD1在口腔黏膜癌前病变和口腔鳞癌中的表达

目的：研究口腔黏膜癌前病变和口腔鳞癌中Stat3和cyclinD1的表达及意义。方法：采用免疫组化方法分别检测正常口腔黏膜、单纯增生黏膜、异常增生黏膜与OSCC中Stat3和cyclinD1表达。结果：正常口腔黏膜、单纯增生、异常增生和OSCC中Stat3和cyclinD1阳性细胞面积指数和IA值逐步升高,Stat3阳性细胞面积指数和IA值除单纯增生与口腔正常黏膜无统计学意义外,其余各组间均有统计学意义;cyclinD1阳性细胞面积指数除单纯增生与正常口腔黏膜、单纯增生与异常增生无统计学意义外,其余各组间均有统计学意义;cyclinD1 IA值除单纯增生与口腔正常黏膜无统计学意义外,其余各组间均有统计学意义。Stat3与cyclinD1阳性细胞面积指数和IA值基本呈线形正相关。结论：Stat3在口腔黏膜癌前病变和OSCC中的表达及与cyclinD1表达的相关性表明,Stat3与cy-clinD1可成为口腔鳞癌早期诊断的标志物和治疗的靶目标。     

PTEN、p53在口腔黏膜白斑和口腔鳞癌组织中的表达及意义

目的:探讨抑癌基因PTEN、p53在口腔黏膜白斑(oralleukoplakia,OLK)和口腔鳞癌(oralsquamouscellcancer,OSCC)组织中的蛋白表达及意义。方法:应用免役组化S-P法检测10例正常口腔黏膜、25例口腔黏膜白斑(其中白斑伴上皮异常增生15例,白斑不伴上皮异常增生10例)及32例口腔鳞癌组织中抑癌基因PTEN和p53的蛋白表达情况,分析两者之间的相互作用关系及其在口腔鳞癌发生、发展过程中的作用。结果:正常口腔黏膜和白斑不伴上皮异常增生组织中PTEN蛋白全部阳性表达;白斑伴上皮异常增生组织中PTEN蛋白阳性表达率为93. 3%;OSCC组织中PTEN蛋白的阳性表达率为71. 9%,其中高、中、低分化OSCC组织中PTEN蛋白的阳性表达率分别为85. 7%、75%和33. 3%,统计学分析表明PTEN在OSCC组织中的蛋白表达与组织分化程度明显相关(P<0. 05)。正常口腔黏膜组织中p53蛋白阴性表达;白斑组织中p53蛋白的阳性表达率为48%;OSCC组织中p53蛋白的阳性表达率为56. 3%,其中高、中、低分化OSCC组织中p53蛋白的阳性表达率分别为57. 1%、58. 3%和50%,统计学分析表明p53在OSCC组织中的蛋白表达与组织分化程度无明显相关(P>0. 05)。p53阴性表达的14例OSCC组织中有5例PTEN也阴性表达。结论:OSCC组织中PTEN和p53蛋白异常表达,说明PTEN和p53基因突变或缺失     

口腔鳞状细胞癌中P27和增殖细胞核抗原的表达

目的:探讨P27和增殖细胞核抗原(PCNA)在口腔鳞状细胞癌(OSCC)中的表达、两指数间的关系以及临床意义.方法:应用免疫组化SP法检测OSCC 55例、正常口腔黏膜上皮组织5例以及异常增生口腔黏膜上皮20 例的P27蛋白和PCNA的表达.结果:P27蛋白及 PCNA在OSCC中的阳性表达率分别为40%,80%,与正常及增生的口腔黏膜上皮相比均有显著差异(P<0.01,P<0.05);两者均与性别、年龄无关(P>0.05);均与临床分期、分化程度、淋巴结是否转移各自相关(P<0.05);两者在OSCC中表达呈负相关(r=-0.510,P< 0.01),在异常增生的口腔黏膜中表达为不相关(r=0.154,P>0.05).结论: P27表达的减弱和PCNA表达增强可以各自成为判定OSCC的恶性程度及预后的指标,深入研究两者的相关关系对OSCC的临床诊断和治疗均有着极为重要的价值.     

口腔黏膜癌变过程中丝氨酸/苏氨酸激酶15的表达及意义

目的了解丝氨酸/苏氨酸激酶15（STK15）在口腔黏膜癌变过程中的表达变化,探讨P53/STK15转激活-非依赖通路在口腔鳞癌（OSCC）发生发展中的作用及意义。方法正常口腔黏膜8例,上皮异常增生患者27例,OSCC患者43例, 石蜡包埋组织,采用免疫组化SABC法了解STK15及P53蛋白表达情况,分析二者的相关性及其临床病理学意义。结果STK15在正常口腔黏膜无表达,在上皮异常增生及OSCC中阳性率分别为40.74%（11/27） 和67.44%（29/43）,各组间差异均有统计学意义（P<0.05）;口腔鳞癌中STK15阳性率在P53阳性组高于P53阴性组,在OSCC有淋巴结转移组高于无淋巴结转移组,差异均有统计学意义（P<0.05）。结论STK15过表达是口腔黏膜癌变过程的早期事件,口腔鳞癌STK15过表达可能与p53突变有关并与OSCC淋巴结转移密切相关,P53/STK15转激活-非依赖通路在OSCC发生发展中可能起重要作用。     

N-乙酰基转移酶10蛋白和朊蛋白在口腔鳞状细胞癌组织中的表达及相关性研究

目的:检测N-乙酰基转移酶10蛋白(Naa10p)和朊蛋白(PrPc)在口腔鳞状细胞癌(OSCC) 、白斑、口腔正常黏膜中的表达及临床意义。方法:应用免疫组化EnvisionTM法检测OSCC(112例)、白斑(42例)及正常黏膜组织(11例)中Naa10p和PrPc的表达情况,并分析其与临床病理特征相关性。结果:Naa10p和PrPc在OSCC表达最高,白斑次之,正常黏膜组织中表达最低。Naa10p在3种不同组织中的表达两两比较均有显著统计学差异(P<0.05),PrPc分别在白斑和OSCC组织,正常口腔黏膜与OSCC组织中的表达有统计学差异(P<0.05)。Naa10p的表达水平与OSCC的TNM分期、淋巴结转移、组织学分化程度密切相关(P<0.05),与性别、年龄无关。PrPc表达仅与组织学分化程度密切相关(P<0.05)。PrPc在OSCC中的表达强度随组织学分化程度下降而明显升高(P<0.05),而Naa10p的表达强度随组织学分化程度下降而明显下降(P<0.05)。结论:Naa10p和PrPc与OSCC的发生和转移相关。     

口腔黏膜癌变过程中Bmi-1及P16蛋白的表达及意义

目的:了解Bmi-1及P16蛋白在口腔黏膜癌变过程中的表达情况,探讨Bmi-1-P16通路在口腔鳞癌发生发展中的作用及意义。方法::正常口腔黏膜10例、上皮异常增生31例、口腔鳞癌61例的石蜡包埋组织,采用免疫组化SP法检测Bmi-1及P16表达情况,分析二者的相关性及其临床病理学意义。结果:Bmi-1在正常口腔黏膜、上皮异常增生及OSCC组织中的阳性率分别为0%、29%(9/31)和62.3%(38/61);P16在正常、上皮异常增生及OSCC组中的阳性率分别为100%(10/10)、77.4%(24/31)和47.5%(29/61)。OSCC中Bmi-1阳性率在P16阴性组高于P16阳性组,差异有统计学意义(P<0.05),Spearman相关分析显示两者间具负相关关系(r=-0.414,P<0.05)。Bmi-1阳性表达及Bmi-1高表达且P16失表达与OSCC临床分期及淋巴结转移密切相关(P<0.05)。结论:Bmi-1过表达是口腔黏膜癌变过程中的早期事件,口腔鳞癌中Bmi-1过表达可能与P16失表达有关并与临床分期及淋巴结转移密切相关,有可能作为临床评估口腔鳞癌浸润、转移和预后的参考指标之一。     

半定量PCR检测口腔鳞状细胞癌凋亡蛋白酶活化因子的表达

目的:探讨凋亡蛋白酶活化因子1(APAF1)基因的表达与口腔鳞状细胞癌(OSCC)的关系。方法:用半定量RT-PCR的方法检测18例正常口腔黏膜组织和32例OSCC组织中APAF1的表达情况。结果:OSCC组织中APAF1的表达显著低于正常口腔黏膜(P<0.01)。结论:APAF1基因可能与OSCC的发生、发展有关,可作为OSCC诊断的检测指标。     

p16INK4A in oral squamous cell carcinomas--a correlation with biological behaviors: immunohistochemical and FISH analysis.

PURPOSE: The p16(INK4A) gene and Rb gene are key tumor suppressor genes in a cell cycle regulatory pathway that is commonly inactivated in various cancers. The disruption of p16(INK4A) expression has been reported in several types of carcinoma but sparse in the area of oral oncology. MATERIALS AND METHODS: The study included 66 cases who were diagnosed as oral squamous cell carcinoma. Immunohistochemical p16(INK4A) and pRb expression, fluorescence in situ hybridization analysis were performed to the resected materials. RESULTS: p16(INK4A) protein expressions were detected in 14 cases without lymph node metastasis versus in 4 cases with metastasis (P = .04). As to histopathological grading of the effect of chemotherapy, almost all the p16(INK4A)-positive cases (9 cases out of 10) exhibited the histological feature of being rather sensitive to chemotherapy (2B and better response according to Ohboshi and Shimosato's criteria) versus 17 of 33 negative cases (P = .02). Survival curves showed that the survival rate of patients with loss of p16(INK4A) expression was significantly worse than those with amplification and normal genetic dosage of p16(INK4A) (P < .0001). CONCLUSIONS: The expressions of p16(INK4A) were significantly correlated with biological behavior of OSCCs. These results indicate we can use p16(INK4A) as a marker of a prognostic prediction of oral cancer and it is useful for management of OSCCs.     

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16(INK4a) in potentially malignant disorders (PMD) of the oral mucosa (with varying degrees of dysplasia) and in oral squamous cell carcinomas (OSCC) to correlate them with the expression of telomerase (hTERT). Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH) were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16(INK4a) expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16(INK4a) expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16(INK4a) and hTERT.     

The clinical significance of CDK1 expression in oral squamous cell carcinoma

Objectives: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. Study Design: Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. Results: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis. Conclusions: The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC. Key words:Cyclin-dependent kinase 1 (CDK1), oral squamous cell carcinoma (OSCC), immunohistochemistry, cell proliferation.     

调控蛋白CDK1对口腔鳞癌预后的评价

目的:研究细胞周期调控蛋白1(cyclin-dependent kinases 1,CDK1)的表达对口腔鳞癌患者预后预测的意义。方法:用SP免疫组织化学法测定77例口腔鳞癌患者CDK1蛋白的表达,并结合患者的术后复发、转移及5年生存率情况进行相关分析。结果:CDK1蛋白阳性表达与口腔鳞癌患者术后复发及淋巴转移关系密切,并有统计学意义(P<0.05);同时患者CDK1蛋白阳性组的5年生存率显著低于阴性组,两组之间有统计学意义(P<0.05),阳性组患者预后更差。结论:CDK1蛋白的表达有希望成为预测口腔鳞癌患者预后的指标之一。     

VEGF、EGFR、p16在唇癌与口腔鳞癌中的表达及临床意义

目的 检测血管内皮生长因子（vascular endothelial factor,VEGF)、表皮生长因子受体（epidermal growth for receptor,ERFR)及p16在唇癌及口腔鳞癌组织中的表达分布特征，探讨其在癌发生发展中的作用及临床病理意义，为唇癌及口腔鳞癌的抗血管生成治疗提供临床病理学依据。方法 应用免疫组化LSAB法检测69例唇癌及口腔鳞癌组织中VEGF、EGFR，p16蛋白的表达及变化。结果 唇癌及口腔鳞癌VEGF、EGFR,p16蛋白表达率分别为71．01％、46．37％及28．98％。不同部位唇癌及口腔鳞癌组织间VEGF、GEFR、p16阳性表达率差异无显著性（P＞0．05）；VEGF在唇癌及口腔鳞癌与非瘤组织中的阳性表达率分别为71．01％、10．00％，二者差异有显著性（P＜0．05）；VEGF、EGFR、p16在唇癌及口腔癌组织中的阳性表达无明显相关（P＞0．05）。结论 唇癌及口腔鳞癌组织中VEGF、EGFRp16之间蛋白表达无相关；VEGF在非瘤组织与唇癌及口腔鳞癌中的表达率差异有显著性；VEGF在唇癌及口腔鳞癌发生发展中起重要作用，可作为有用的标志物。     

Twist、Snail、Slug在口腔鳞状细胞癌中的表达及其与各临床病理因素的关系

目的:探讨Twist、Snail、Slug在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达水平及其与各临床病理因素之间的关系.方法:采用免疫组织化学方法检测术前未接受放化疗的有颈部淋巴结转移或无颈部淋巴结转移的60例原发OSCC患者肿瘤切除石蜡标本中Twist、Snail、...     

Expression of p16 in oral cancer and premalignant lesions

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.
Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.
Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.
Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.     

Aberrant expression of p53, p16INK4a and Ki‐67 as basic biomarker for malignant progression of oral leukoplakias

J Oral Pathol Med (2011) 40 : 629–635 Background: The risk of malignant progression of oral leukoplakia with and without dysplasia is unpredictable. Materials and methods: Leukoplakias without dysplasia of 35 patients, leukoplakias with dysplasia of 4 patients, and similar lesions obtained from tumor patients were retrospectively examined by immunohistochemistry for the expression of the proteins pRb, p53, p16^INK4a, Cyclin D1 and Ki‐67. The predictive power of combined aberrant expression patterns for the progression of leukoplakias without dysplasia was examined. Results: Increased expression of p53, Ki‐67 and Cyclin D1, and loss of p16^INK4a occurred in 45.9%, 38.9%, 29.4% and 32.4% of the leukoplakias without dysplasia, respectively. All alterations increased with progression but had poor positive predictive value. However, the combined p53/p16^INK4a/Ki‐67 aberration occurred in only three (9%) cases, of which two patients (66.7%) experienced progression to dysplasia and carcinoma in situ. The combined p53/p16^INK4a/Ki‐67 alteration had a negative predictive value (NPV) and sensitivity of 100%, specificity of 97% and positive predictive value (PPV) of 67%. By contrast, the combined p53/p16^INK4a/Cyclin D1 alteration had 97% NPV and sensitivity of 50%, specificity of 90% and only 25% PPV. Loss of pRb and concomitant overexpression of p16^INK4a were not observed arguing against an involvement of HPV in oral leukoplakia. Conclusions: We propose the combined p53/p16^INK4a/Ki‐67 alteration as a basic marker to define high risk leukoplakia patients. Lesions not showing this alteration appear to be harmless. Future studies should validate these findings and search for proteins which can further improve the PPV of the proposed basic marker.     

丝/苏氨酸蛋白激酶/哺乳动物雷帕霉素靶蛋白/p70 S6K信号通路在口腔鳞癌中的表达及临床意义

目的 探讨丝/苏氨酸蛋白激酶（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）/p70 S6K信号通路在口腔鳞癌组织中的表达情况,为口腔鳞癌的早期诊断和治疗提供参考。方法 收集口腔鳞癌标本51例,癌旁黏膜组织10例,正常口腔黏膜10例。采用免疫组织化学SP法检测口腔鳞癌、癌旁黏膜组织及正常口腔黏膜中p-Akt、p-mTOR及p70 S6K的表达情况,分析三者相互之间表达的相关性。结果 p-Akt、p-mTOR及p70 S6K在口腔鳞癌组中的表达显著高于正常口腔黏膜组和癌旁黏膜组的表达。p-Akt、p-mTOR及p70 S6K在口腔鳞癌的表达与患者的年龄、性别及临床分期无相关性,但与口腔鳞癌的分化程度及有无淋巴结转移有相关性。p-Akt、p-mTOR及p70 S6K在口腔鳞癌的表达相互之间具有较强的正相关关系。结论 Akt/mTOR/p70 S6K信号通路分子在口腔鳞癌中表达活跃,提示可能与口腔鳞癌的发生发展具有重要的相关性。