舌鳞状细胞癌浸润前沿细胞增殖的研究

目的　研究舌磷癌浸润前沿分级、检测增殖细胞核抗原 (PCNA)、Ki6 7、核仁组织区相关嗜银蛋白 (AgNOR)在浸润前沿中的表达。 方法　对 5 7例舌鳞癌行浸润前沿分级 ,采用免疫组化SP法及银染色法检测浸润前沿和中心PCNA、Ki6 7、NORs的表达。结果　浸润前沿PCNA、Ki6 7的表达和AgNOR均数均明显高于非前沿部分 ,差异有极显著性 (P <0 .0 0 1) ;浸润前沿PCNA标记指数 (P <0 .0 5 )、AgNOR均数 (P <0 .0 1)与浸润前沿分级 (IFG)总分呈正相关关系 ;单因素COX分析显示 ,IFG总分 (P <0 .0 1)、浸润前沿AgNOR均数 (P <0 .0 5 )对判断预后有意义 ;多因素COX分析显示 ,IFG总分 (P <0 .0 1)可作为预测总体生存率和累积生存率的有意义的因子。结论　舌鳞癌浸润前沿肿瘤细胞分化较差 ,增殖活性明显高于非前沿部分 ;IFG总分和浸润前沿AgNOR均数与舌癌预后有关     

上皮钙粘素与β连环素在口腔鳞癌浸润前沿表达的研究

目的:研究上皮钙粘素(Ecad)和β连环素(cat)在口腔鳞状细胞癌(OSCC)浸润前沿的表达及意义。方法:应用免疫组化(SP)方法检测52例口腔鳞癌中Ecad和βcat的表达,比较二者在癌浸润前沿、非前沿及癌旁黏膜的表达。结果:口腔鳞癌Ecad、βcat的表达低于癌旁黏膜,癌前沿区蛋白表达显著下降。前沿区Ecad(P<0.01)、βcat(P<0. 01)表达明显低于非前沿部分。Ecad的表达与肿瘤分化程度呈正相关(P<0. 01);前沿区Ecad的表达与IFG总分相关(P<0. 01)。结论:口腔鳞癌浸润前沿区Ecad、βcat较非前沿部分降低明显;Ecad的表达与肿瘤分化程度相关。     

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.     

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.     

增殖细胞核抗原和Ki-67抗原在涎腺癌中的表达

目的:探讨细胞增殖核抗原和Ki-67抗原在不同类型涎腺癌中的表达及意义。方法:采用SABC和LSAB免疫组化法分别检测PCNA和Ki-67在17例粘液表皮样癌、12例腺样囊性癌、9例恶性多形性腺瘤中的表达和分布。结果:1)PCNA及Ki-67的增殖指数即PI值在粘液表皮样癌和腺样囊性癌的不同分级中表达不同,且有统计学意义(P<0.005)。2)恶性多形性腺瘤PCNA及Ki-67的PI值较高,与腺样囊性癌及粘液表皮样癌相比差异有统计学意义(P<0.001)。3)PCNA及Ki-67的表达水平与涎腺癌的生物学行为(复发和转移)明显相关。结论:涎腺癌中PCNA和Ki-67的表达水平与细胞分化有关,其PI值可作为粘液表皮样癌和腺样囊性癌的组织学分级的重要参数,也是诊断恶性多形性腺瘤的重要指标。PCNA和Ki-67的高表达预示着涎腺癌预后的不良。     

IL-18在口腔鳞状细胞癌中的表达

目的:探讨白介素18在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达.方法:采用酶联免疫反应(ELISA)方法检测30例口腔鳞癌及10例正常人血清中IL-18的表达水平;免疫组织化学SP法检测36例口腔鳞癌组织和10例正常口腔黏膜组织中IL-18蛋白的表达.结果:口腔鳞癌患者血清中IL-18表达水平高于对照组(P<0.05).中、低分化患者血清中IL-18水平明显高于高分化者(P<0.05);IL-18的水平随肿瘤浸润范围的扩大有逐渐升高的趋势,但无统计学意义(P>0.05).癌组织中IL-18表达的阳性率低于正常的黏膜组织(P<0.05).癌细胞分化程度越高,IL-18的表达越强(P<0.05),19例癌组织中IL-18弱表达或不表达,均是中、低分化者.血清中IL-18的表达量与癌组织中的阳性率呈反比.结论:IL-18在口腔鳞癌患者血清中表达明显升高,癌组织中表达下降,二者呈负相关,并且IL-18的表达与癌细胞的分化程度关系紧密,可作为判断口腔鳞癌病理分级的重要参考指标之一.     

基质金属蛋白酶抑制剂-1在口腔疣状癌中的表达研究

目的观察基质金属蛋白酶抑制剂(tissue inhibitor of metalloproteinase,TIMP)-1在口腔疣状癌(OVC)中的表达。方法选择15例口腔疣状癌、10例正常口腔黏膜、20例口腔鳞癌标本(高、低分化鳞癌各10例),应用免疫组化S-P法检测TIMP-1的表达和分布。结果口腔疣状癌组织中TIMP-1阳性表达率为80%(12/15),高于高分化鳞癌(60%,6/10)和低分化鳞癌(40%,4/10)(P<0.05);平均染色强度高于高、低分化鳞癌(P<0.05);口腔疣状癌、口腔高分化鳞癌、口腔低分化鳞癌组织中TIMP-1的表达均高于正常口腔黏膜组织(P<0.05)。结论OVC是一种不同于口腔鳞状细胞癌的独立类型的恶性肿瘤,TIMP-1可以抑制肿瘤的浸润与转移。     

增殖细胞核抗原和Ki-67抗原在黏液表皮样癌中的表达

目的:检测细胞增殖核抗原(PCNA)和Ki-67抗原在黏液表皮样癌中的表达,探讨其表达量与粘液表皮样癌分级的相关性及意义。方法:对17例黏液表皮样癌的临床病理特点进行回顾性分析,采用SABC和LSAB免疫组化法分别检测PCNA和Ki-67在17例黏液表皮样癌的表达和分布。结果:17例黏液表皮样癌中,高分化型11例(其中1例转移)。低分化型6例(其中4例转移)。PCNA及Ki-67的增殖指数(PI值)在黏液表皮样癌中,低分化型明显高于高分化型(P<0.001)。在发生转移的黏液表皮样癌组中,PCNA及Ki-67的表达水平均明显高于无转移组。结论:黏液表皮样癌中PCNA和Ki-67的表达水平与细胞分化有关,其PI值可作为组织学分级的重要参数。PCNA和Ki-67的高表达预示着黏液表皮样癌预后的不良。     

口腔黏膜鳞状细胞癌端粒酶活性与PCNA表达的关系

目的 :探索口腔黏膜鳞状细胞癌端粒酶活性与增殖细胞核抗原 (PCNA)表达的关系。方法 :应用TRAP PCR ELISA方法及免疫组化SP法对 68例口腔黏膜鳞状细胞癌组织、3 4例癌旁上皮组织和 12例正常口腔黏膜组织进行检测。结果 :口腔黏膜鳞状细胞癌组织中端粒酶表达阳性率为 67.65 % ( 4 6/ 68) ;癌旁组织中端粒酶表达率为 8.82 % ( 3 / 3 4) ;正常口腔黏膜组织中无端粒酶活性表达。口腔黏膜鳞状细胞癌组织端粒酶活性表达与临床病理分级有关 ;端粒酶活性阳性的 46例癌组织和 3例癌旁上皮异常增生组中PCNA阳性细胞密度为 ( 165 .3 1± 1.82 )个 /mm2 ,端粒酶阴性的 2 2例癌组织和 10例癌旁上皮异常增生组中PCNA阳性细胞密度为 ( 96.77± 1.74)个 /mm2 。端粒酶活性阳性组与阴性组之间PCNA阳性细胞密度差异有统计学意义 (P <0 .0 1)。结论 :端粒酶活性与口腔黏膜鳞状细胞癌发生、发展密切相关 ;端粒酶活性与PCNA阳性表达有关     

新辅助化疗前后PCNA和p53在口腔鳞癌中的表达及其对化疗敏感性的预测研究

目的:探讨新辅助化疗前后增殖细胞核抗原(PCNA)和抑癌基因p53在口腔鳞癌组织中的表达水平及其与化疗疗效的关系.方法:采用SP免疫组化法,对106例口腔鳞癌患者新辅助化疗前后的PCNA和p53表达水平进行检测,分析其表达水平与化疗疗效的关系.结果:①化疗前口腔鳞癌组织中PCNA高表达率为50.94%,显著高于化疗后23.58%(P<0.05);化疗前PCNA高表达患者化疗有效率为62.96%,显著高于PCNA低表达患者的有效率30.77%(P<0.05);②化疗前p53在口腔鳞癌中的阳性表达率为44.34%,显著高于化疗后21.60%(P<0.05);化疗前口腔鳞癌p53表达阴性患者的有效率为55.93%,显著高于p53表达阳性患者的有效率36.17%(P<0.05).结论:新辅助化疗可明显降低PCNA和p53在口腔鳞癌组织中的表达水平,PCNA和p53的表达水平与新辅助化疗疗效具有显著的相关性,认为PCNA和p53的表达水平有可能成为口腔鳞癌化疗疗效的预测指标.     

The relationship of the histologic grade at the deep invasive front and the expression of Ki-67 antigen and p53 protein in oral squamous cell carcinoma

BACKGROUND: Although many histopathologic characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, accurate, and unequivocal factors have not been clearly identified. The purpose of this study was to evaluate a potential association between the histologic grade of malignancy at the deep invasive front and the expression of Ki-67 antigen and p53 protein in O-SCC. METHODS: The expression of Ki-67 antigen and p53 at the invasive tumor front area of O-SCC was examined by immunohistochemistry of archived tissue from 62 cases. The mean age of patients was 60.7 years (range: 37-89) and the male-female ratio was 1.6:1 (38 men, 24 women). There were 20, 17, 14, and 11 cases classified as stage I to stage IV, respectively. The correlation between the intensity of immunostaining for Ki-67 antigen and p53 and the histologic grade of malignancy at the deep invasive front (invasive front grade, IFG) was analyzed. The expression of Ki-67 antigen and p53 in normal oral epithelia (10 cases) was also investigated. RESULTS: The mean Ki-67 labeling index (LI) in the O-SCC samples was 32.8 +/- 12.0% (n = 62). The mean total score of IFG (IFG score) was 9.1 +/- 2.7 points (n = 62). There was a significant linear correlation between the IFG score and the Ki-67 antigen (gamma = 0.651, R2 = 0.596, P < 0.0001). Of 50 tumors examined, 27 (54.0%) exhibited p53-positive nuclear immunostaining. The staining patterns for Ki-67 antigen and p53 were similar. Both Ki-67-LI and p53-positive status were significantly correlated with the IFG scores. CONCLUSION: The findings of this study demonstrate that overexpression of Ki-67 antigen and p53 at the deep tumor invasive front of O-SCC is associated with histologic grade of malignancy.     

Analysis of the Ki-67 antigen at the invasive tumour front of human oral squamous cell carcinoma

BACKGROUND: It is hypothesised that cell proliferation, as measured by the Ki-67 labelling index (LI) at the invasive tumour front (ITF) was directly related to the histological grade in human oral squamous cell carcinomas (SCCs). METHODS: Tissues from 42 human oral SCCs were collected and stained with an antibody directed against the Ki-67 antigen using an advanced polymer staining system. Quantitation of the immunopositive cells was performed on two parallel sections at the invasive tumour front (ITF), using an image analyser. The Ki-67 LI was expressed as the number of positive nuclei/mm2 of epithelium. The control tissue used was normal epithelium at the excision margin. RESULTS: The mean Ki-67 LI for oral SCCs at the ITF was significantly greater than that for the excision margin tissue (P < 0.0001). There was a positive association between increasing Ki-67 LI and increasing Broders' grade (P < 0.05), with a well-differentiated tumour having the lowest mean Ki-67 LI (1549 +/- 806) and a poorly differentiated tumour having the highest value (2232 +/- 771). A similar trend was observed between the mean Ki-67 LI and Bryne's multifactorial grading system. CONCLUSIONS: It was concluded from this study that cell proliferation (as measured by the Ki-67 antigen) at the ITF had a strong positive relationship with histological grading in human oral SCC.     

Analysis of cell proliferation and pattern of invasion in oral squamous cell carcinoma

Cell proliferation markers play an important role in the biological behavior of neoplasms. This study investigated the immunohistochemical expression of PCNA, Ki-67 and Cyclin B1 proteins based on the pattern of cell invasion in oral squamous cell carcinoma (OSCC). A total of 39 OSCC specimens and 13 samples of normal oral mucosa (control) were immunohistochemically analyzed. Protein expression was evaluated according to World Health Organization - Histological Malignancy Grading (WHO-HMG) and a specific grading system for invasion, graded from 1 to 4, varying from a consistently well-defined "pushing" border to diffuse infiltration and cellular dissociation, and was then correlated with clinical features. We found higher expression of Ki-67 and Cyclin B1 in OSCC when compared with the control group. High Ki-67 expression levels were more commonly seen in the floor of the mouth than in the tongue (P = 0.009). Cyclin B1 showed a positive correlation with histological grade, according to WHO-HMG criteria (P = 0.01). Our results suggest that Cyclin B1 is a reliable proliferation marker for indicating degree of tumor proliferation. Correlations between PCNA, Ki-67, Cyclin B1 and invasive tumor front with overall survival were not observed. Further studies are needed in order to elucidate whether cell proliferation activity at the tumor invasion front is related to prognosis.     

The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma

BACKGROUND: We hypothesise that the density of proliferating cells at the invasive tumour front (ITF) has a positive relationship with prognostic and risk factors in human oral squamous cell carcinoma (SCC). METHODS: Tissues from 47 human oral SCC specimens were collected and stained with a monoclonal antibody directed against the Ki-67 antigen using a horseradish peroxidase based two-step immunostaining method. Counting was performed on two parallel sections at the ITF using an image analyser. The Ki-67 labelling index (LI) was determined by measuring the number of nuclei/mm(2) of epithelium. RESULTS: Our results show that the density of proliferating cells is related to clinical staging, with advanced stage of disease having a significantly higher Ki-67 LI compared with early stage of disease (2111 +/- 905 vs. 1908 +/- 913; P = 0.03). Importantly, this study shows that tumours that have metastasised have a significantly higher Ki-67 LI than tumours where distant metastasis was not detected (3257 +/- 650 vs. 1966 +/- 881; P < 0.0001). CONCLUSIONS: Cell proliferation, as measured by the Ki-67 LI at the ITF, has a positive relationship with clinical staging, tumour thickness, smoking status of the patient and alcohol consumption. Further, we suggest that a multicenter study with a large cohort of patients is indicated to fully elucidate whether cell proliferation at the ITF is directly related to patient survival.     

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.     

Invasive front in oral squamous cell carcinoma: image and flow cytometric analysis with clinicopathologic correlation

OBJECTIVE: Pathologists have drawn attention to the invasive tumor front (ITF) in the determination of the biologic aggressiveness of oral cancer. We have attempted to discover the prognostic significance of cancer cells with abnormal DNA content at the ITF of oral squamous cell carcinoma. STUDY DESIGN: A comparative DNA analysis by means of image cytometry and flow cytometry was conducted to confirm the usefulness of image cytometry in detecting cancer cells having abnormal DNA content at the ITF. The prognostic value of cancer cells with abnormal DNA content ws examined by a multivariate analysis for 195 patients with oral squamous cell carcinoma. RESULTS: In the comparative DNA analysis, it was suggested that image cytometry is useful for detecting cancer cells with abnormal DNA content (4c exceeding rate [4cER]), which is associated with poor prognosis of patients with oral squamous cell carcinoma. In the multivariate analysis, 3 independent factors were found to significantly influence cause-specific survival. These are, in decreasing order of influence, (1) abnormal DNA content (4cER), (2) clinical stage, and (3) growth type. CONCLUSION: The presence of cancer cells with abnormal DNA content of the ITF in conjunction with clinical findings (clinical stage and growth type) can give additional useful information when selecting treatment strategies for oral cancer patients.     

口腔白斑癌变过程中整合素β1的表达及其与细胞增殖的关系

目的 探讨整合素β1在口腔白斑癌变发生、发展中的可能作用及其与细胞增殖的关系.方法 免疫组化SP法研究整合素β1及Ki-67在12例正常口腔黏膜、10例单纯增生白斑、24例异常增生白斑、14例早期浸润癌组织中的表达情况及关系.结果 在正常黏膜及单纯增生白斑中整合素β1表达于基底及副基底层细胞的胞膜;Ki-67在基底及副基底层的胞核中表达.在异常增生白斑及早期浸润癌中可见整合素β1表达于基底层、增生的棘层细胞及癌细胞胞膜;Ki-67表达于基底层、增生的棘层细胞及癌细胞的胞核.整合素β1在异常增生及早期浸润癌中的强阳性表达率分别为29%(7/24)、57%(8/14);Ki-67在异常增生及早期浸润癌中的强阳性表达率分别为42%(10/24)、57%(8/14).整合素β1、Ki-67在4组病变之间的阳性分级差异有统计学意义(χ2=10.651,P=0.014;χ2=14.831,P=0.002);整合素β1在正常黏膜、单纯增生组与早期浸润癌组之间的差异有统计学意义(P=0.008,P=0.013).Ki-67在正常黏膜组与异常增生组、早期浸润癌组之间差异有统计学意义(P=0.026,P=0.001),单纯增生组与早期浸润癌组之间差异有统计学意义(P=0.005).整合素β1与Ki-67的表达显著相关(R=0.442,P＜0.01).结论 整合素β1在口腔白斑异常增生及早期浸润癌中表达增强,可能与促进细胞增殖有关.