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。     

E-cad、CD44V6在口腔鳞癌组织中的表达及其相关性研究

目的 :分析E 钙粘蛋白 (E cadherin ,E cad)和CD44V6在口腔黏膜鳞癌及其癌变过程中的表达规律 ,探讨它们的异常表达与口腔黏膜癌变、转移的关系。方法 :采用免疫组织化学SP法分别检测E cad、和CD44V6在 17例正常口腔黏膜、6例口腔黏膜异常增生和 5 2例口腔黏膜鳞癌的不同表达。结果 :其中 ,E cad在正常口腔黏膜、口腔黏膜异常增生的阳性表达率明显高于在口腔黏膜鳞癌中的阳性表达率 ;而CD44V6在正常口黏膜、口腔黏膜异常增生的阳性表达率明显高于在口腔黏膜鳞癌中的阳性表达率 ;同时 ,E cad的阳性表达率随肿瘤的分化程度降低而降低 ,CD44V6的阳性表达率随肿瘤的分化程度降低而升高 ;E cad和CD44V6之间的关系表现为负相关 ,同时 ,CD44V6与肿瘤的转移密切相关。结论 :E cad和CD44V6在口腔黏膜鳞癌的分化和转移过程中起重要作用 ,CD44V6的表达与肿瘤的不良分化和转移密切相关 ,而E cad的表达则对患者有保护趋势。     

CD44在口腔鳞癌中的表达

目的初步探讨CD44分子在口腔鳞癌中的表达情况。方法以免疫组织化学方法对22例口腔不同部位的鳞癌及其周边扩大切除的组织进行了观察研究,并和癌组织的病理分级进行对比分析。结果 CD44表达在正常口腔粘膜表皮的基底细胞和部分棘层细胞的细胞膜上,同时在淋巴细胞上强表达。在鳞癌上皮组织中CD44的表达模式发生紊乱,表达水平与细胞分化程度有关,病理分化度较差的癌组织中CD44的表达逐渐减弱。结论 CD44可以作为评价口腔鳞癌恶性度的一个指标。     

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.     

CD44和CD133在口腔潜在恶性病变和口腔鳞状细胞癌中的表达及其临床意义

目的 探究肿瘤干细胞标记物CD44和CD133在口腔正常黏膜、口腔潜在恶性病变（OPMD）及口腔鳞状细胞癌（OSCC）中的表达情况及相互关系,评估其作为OPMD恶性转化早期诊断指标的临床价值。方法 回顾性分析60例OPMD患者、60例OSCC患者及10例口腔黏膜正常者的临床资料,采用免疫组织化学双重染色技术检测各组病理组织中CD44与CD133的表达,分析CD44和CD133表达之间的关系及其与各临床因素之间的关系。结果 口腔正常黏膜、OPMD、OSCC三组中,CD44的阳性表达率分别为100.00%、96.67%、71.67%（P<0.05）,CD133的阳性表达率分别为0.00%、35.00%、63.33%（P<0.05）。CD44与CD133二者间的表达具有相关性（P<0.05）,且其表达又都与OSCC的临床分期和淋巴结转移相关（P<0.05）。结论 CD44和CD133作为评估OPMD恶性转化潜能的指标具有重要临床价值。     

舌鳞癌组织中CD44v6、CD44v3表达与预后的关系

目的:研究舌鳞癌组织中CD44v3及CD44v6的表达及与预后之间的关系,探讨CD44v3及CD44v6作为预测舌鳞癌预后指标的可能性.方法:应用免疫组织化学方法检测68例单纯手术治疗的舌鳞癌石蜡标本中CD44v3及CD44v6的表达,分析CD44v3及CD44v6的表达与舌鳞癌患者的年龄、性别、临床分期、肿瘤分化程度、淋巴结转移等临床病理因素及预后的关系,采用SPSS11.0软件包对数据进行统计学处理,并绘制Kaplan-Meier生存曲线.结果:(1)生存期≤2年的舌鳞癌组患者CD44v3阳性细胞百分率及CD44v6阳性细胞百分率均高于生存期≥5年组(P值分别为0.049和0.004).(2)多因素Cox模型分析显示,只有淋巴结转移可作为舌鳞癌预后的独立预测因子(P值分别为0.048和0.011).(3)Kaplan-Meier生存分析表明,舌鳞癌组织中CD44v6和CD44v3阳性强度越高,患者的平均生存时间越短.但经Log Rank(Mantel-Cox)检验.均无统计学意义.结论:舌鳞癌组织中CD44v3或CD44v6的表达与预后不良关系密切,但尚不能证明可作为舌鳞癌预后的独立预测因子.     

p73在口腔黏膜白斑和口腔鳞癌中的表达

目的：观察p73在口腔黏膜白斑和口腔鳞癌中的表达,了解p73在口腔鳞癌发生过程中的变化规律。方法：白斑病理标本20例,口腔鳞状细胞癌病理标本31例,另取正常口腔黏膜10例,采用免疫组化检测方法观察p73的表达。应用SPSS11.0软件包对实验结果进行χ^2检验和单因素方差分析。结果：口腔白斑和口腔鳞癌病变组织中p73的表达率分别为65%和90.3%,均显著高于正常黏膜组（20%）,且随组织恶性程度增高呈明显上升趋势,正常黏膜上皮组、白斑组与鳞状细胞癌3组间比较,差异有统计学意义（P〈0.05）。结论：p73的表达与口腔鳞癌的癌变过程密切相关,可作为口腔白斑癌变的标志物。     

P75神经营养因子受体在口腔鳞状细胞癌中的表达及意义

目的:研究口腔鳞状细胞癌中p75神经营养因子受体(p75NTR)的表达,探讨p75NTR作为预测口腔鳞状细胞癌预后指标及将其作为肿瘤干细胞标志物的可能性。方法:采用SP免疫化学方法,对舌鳞状细胞癌细胞系Tca8113及43例手术切除口腔鳞状细胞癌标本进行p75NTR表达的检测,另外选取5例癌旁组织及8例正常组织作为对照。应用SPSS16.0软件包,采用行×列表资料的χ2检验进行统计学分析。结果:p75NTR在Tca8113细胞膜中阳性表达。43例口腔鳞状细胞癌组织中,p75NTR阳性表达33例,在癌旁组织及正常对照组中没有表达。p75NTR均定位于细胞膜上,于癌巢中分散分布,且常有聚集性分布趋势。p75NTR表达与临床分期(P<0.05)及有无淋巴结转移(P<0.05)相关。结论:p75NTR的表达可以作为预测口腔鳞状细胞癌预后的指标,但还不能将其单独作为肿瘤干细胞的标志物,其在肿瘤发生、发展中的作用及机制仍需进一步研究。     

Expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated vascular endothelial cells: A relationship to tumor angiogenesis

BackgroundOral squamous cell carcinoma is characterized by high degree of local invasion with metastasis as well as characteristic angiogenic features. Angiogenesis is a critical step in the growth and metastasis of tumors. Cluster of differentiation 44 (CD44) is a cell surface glycoprotein which is widely expressed in both physiological and pathological conditions.AimThe study was designed to assess the expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated endothelial cells and to correlate this expression with matrix metalloprpteinase-9 (MMP-9) and transforming growth factor-beta (TGF- β) expression immunohistochemically.Materials and methodsOne hundred fourteen archival oral squamous cell carcinoma cases were used in this study. Immunohistochemistry was performed for CD44 (NKI-P1), Ki-67, cluster of differentiation 31(CD31), podoplanin (D2-40), MMP-9 and TGF- β. Microvessel density was also determined morphologically. Results: CD44 was expressed in (CD31+/ Podoplanin –) blood vascular endothelial cells in a strong cytoplasmic fashion. In addition, the extracellular matrix proteins (MMP-9 and TGF-β were expressed in oral squamous cell carcinoma stroma which was enriched with CD44 + blood vessels. The mean numbers of microvessel density in connective tissue beneath normal epithelium and different grades of oral squamous cell carcinoma stroma were 5.8, 22.1, 22.4 and 23.5, respectively with the P-value < 0.05, where a significant statistical difference between microvessel density in the connective tissue beneath normal epithelia and stroma of all grades of oral squamous cell carcinoma was found. Conclusion: CD44 (NKI-P1) is considered a potential marker of oral squamous cell carcinoma angiogenesis and it can be used as a valuable biomarker of tumor invasion and as a therapeutic target for anti-angiogenic therapies.     

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.     

Reduced expression of the CD44 variant exons in oral squamous cell carcinoma and its relationship to metastasis

In the present study, we examined the expression of CD44 variant exons in human oral squamous cell carcinoma (OSCC). Of ten cell lines from OSCCs, two (KB and H357), as well as the HeLa cell line, failed to express CD44 variant exons. In surgical specimens, all normal mucosa expressed CD44v9 (both mRNA and protein). Of 40 primary OSCCs, 19 (47.5%) showed downregulation of CD44v9, which correlated with tumor cell differentiation, primary metastasis to lymph nodes and secondary metastasis to lymph nodes. The results suggest that the downregulation of CD44v9 may play a role in lymphatic metastasis of OSCC and changes in its expression may be a useful diagnostic tool to determine the metastatic potential of OSCC to lymph nodes. Moreover, three cell lines that failed to express CD44 variant exons might become a useful experimental model to study the role of variant exons in the progression of OSCC.     

Cancer stem cell immunophenotypes in oral squamous cell carcinoma

J Oral Pathol Med (2011) 40 : 135–142 Background: The presence of cancer stem cell (CSC) antigens can be evidenced in some human tumors by phenotypic analysis through immunostaining. This study aims to identify a putative CSC immunophenotype in oral squamous cell carcinoma (OSCC) and determine its influence on prognosis. Methods: The following data were retrieved from 157 patents: age, gender, primary anatomic site, smoking and alcohol intake, recurrence, metastases, histologic classification, treatment, disease‐free survival (DFS), and overall survival (OS). An immunohistochemical study for CD44 and CD24 was performed in a tissue microarray of 157 paraffin blocks of OSCCs. Results: In univariate analysis, the immunostaining pattern showed significant influences in relation to OS for alcohol intake and treatment, as well as for the CD44⁺ and CD44^?/CD24^? immunophenotypes. The multivariate test confirmed these associations. Conclusions: Based on our results, the CD44 immunostaining and the absence of immunoexpression of these two investigated markers can be used in combination with other clinicopathologic information to improve the assessment of prognosis in OSCC.     

Expression of CD44 variant exons by primary and metastatic oral squamous carcinomas

Abnormal CD44 expression in many neoplasms correlates with behaviour, but reports on its role in oral squamous carcinoma are contradictory. CD44 expression was characterised in a closely matched series of oral carcinomas with and without metastases in both frozen and formalin-fixed tissue and correlated with behaviour and histological grading parameters. Eleven primary oral squamous carcinomas without metastases and nine primary carcinomas with 19 matched metastases were stained immunocytochemically for CD44H and products of variant exons v3, v4/5, v6 and v9. Patterns of staining in frozen and formalin-fixed tissue were correlated with invasive front grading and behaviour using exact inferential statistics. Most primary carcinomas stained for all exons tested but some showed loss of expression of v4/5. Loss of expression was more marked in metastases, but there was no correlation between expression and behaviour or grade. Stromal surfaces of epithelial cells often expressed variant exon products reflecting loss of polarity. This, together with selective loss of v4 and v5 in primary carcinomas and their more frequent loss in metastases, suggests that CD44 may play a role in metastasis of some oral squamous carcinomas.     

p63在口腔扁平苔藓中的表达

目的探讨p53家族新成员p63在口腔扁平苔藓（OLP）中的表达，其与OLP发生、发展的关系以及是否可作为一种标志物预测OLP的转归。方法采用免疫组织化学方法检测30例012中p63蛋白的表达，同时采用RT—PCR方法分析p63编码的两大类转录产物TAp63和ANp63的mRNA水平，并且与口腔鳞状细胞癌（OSCC）及正常口腔黏膜（NOM）进行比较。结果p63蛋白在NOM、OLP和OSCC组中均有表达，与NOM比较，其累积光密度（IOD）值在OLP中下调，在OSCC中明显上调。在糜烂萎缩型OLP中，p63蛋白表达高于非糜烂型（P〈0．001）。RT-PCR检测结果显示，TAp63的mRNA水平在OLP中表现为中等。略低于NOM．明显高于OSCC；ANp63的mRNA水平在NOM和OLP中极低．其转录扩增带大多数检测不到．但在OSCC组都能检测到．而且呈高水平表达。TAp63的mRNA水平在糜烂萎缩型OLP中低于非糜烂型（P=0．018），ANp63则高于非糜烂型（P=0．049）。结论p63与OLP的发病机制有关，其中TAp63和ANp63分别起不同的作用。p63表达的高低可能可以作为预测OLP是否有高风险癌变的检测指标。     

CD44v3及CD44v6在舌鳞癌组织中的表达及意义

目的探讨CD44v3及CD44v6在舌鳞癌组织中的表达及其与临床病理因素的关系。方法免疫组织化学方法检测中山大学附属第二医院口腔颌面头颈外科1996年1月至2006年12月单纯接受手术治疗的71例舌鳞癌石蜡标本中CD44v3及CD44v6的表达．用SPSS13．0统计软件分析CD44v3及CD44v6的表达与舌鳞癌患者的年龄、性别、临床分期、肿瘤分化程度、淋巴结转移等临床病理因素的关系。结果（1）舌鳞癌组织中CD44v3及CD44v6阳性百分数均高于癌旁组织中CD44v3及CD44v6阳性百分数（P〈0．001）。（2）舌鳞癌组织中CD44v3及CD44v6阳性百分数有统计学相关（Speamlan相关系数为0．494．P〈0．001）。（3）淋巴结转移与无淋巴结转移组间舌鳞癌CD44v3及CD44v6阳性强度差异均有统计学意义（P值分别为0．023及0．019）。结论舌鳞癌CD44v3及CD44v6表达与淋巴结转移有关。检测它们有助于判断患者的预后。     

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.