骨形成蛋白信号通路中Smad4和Smad7在口腔鳞癌中的表达变化

目的：观察口腔鳞癌和癌旁正常组织中Smad4和Smad7表达量的变化,探讨Smad4和Smad7对口腔鳞癌发生和发展的影响。方法：收集临床和病理学诊断为OSCC的病例72例。取癌组织和癌旁正常组织做切片,用SP免疫组化法分别检测Smad4和Smad7在口腔鳞癌和正常组织中的表达,采用SPSS11.5软件包对数据进行统计学分析。结果：Smad4蛋白在癌旁正常组织中的阳性表达率为69.44%,在口腔鳞癌组织中的阳性表达率为45.83% (P<0.05),且随着分化程度的降低其阳性表达率降低;有淋巴结转移者阳性表达率为22.50%,无淋巴结转移者阳性表达率为65.63% (P<0.05)。Smad7蛋白在癌旁正常组织中的阳性表达率为19.44%,在口腔鳞癌组织中的阳性表达率为83.33%(P<0.05),且随着分化程度的降低其阳性表达率升高;有淋巴结转移者阳性表达率为92.50%,无淋巴结转移者阳性表达率为68.75% (P<0.05)。结论：Smad4在癌组织中表达明显减少,且分化程度越低,表达越少,Smad4在有淋巴结转移的组织中比在无淋巴结转移的组织中表达低;Smad7的作用则相反。Smad4的表达缺失可能促进了口腔鳞癌的发展和转移,Smad7的过表达促进了口腔鳞癌的发展和转移;BMP/Smads信号传导通路受到抑制,可能会导致口腔鳞癌的继续发生和发展。     

Maspin expression in oral squamous cell carcinoma

Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily of protease inhibitors and it has a role as a tumor suppressor. Maspin has been reported to be important in processes relevant to tumor growth and metastasis such as cell invasion, angiogenesis, and apoptosis. A high expression of maspin was correlated with better rates of survival and absence of nodal metastases in head and neck squamous cell carcinoma. In contrast, some studies have shown that maspin overexpression is correlated with a poor prognosis in pancreatic and ovarian cancers and in lung adenocarcinoma. The aim of this study was an immunohistochemical evaluation of the maspin expression in oral squamous cell carcinoma and thus 89 patients were evaluated. Maspin expression in oral squamous cell carcinoma was significantly associated with the tumor differentiation grade (chi test: P = 0.0318) and the lymph node status (chi test: P < 0.005), but not with the tumor stage (chi test: P = 0.666). Metastatic involvement of lymph nodes was observed more frequently in maspin-negative cases than in tumors with more than 5% of positive cells (P = 0.0024). The present results confirm that maspin expression predicts a better prognosis in oral squamous cell carcinoma and that maspin probably plays a role in tumor progression.     

透明质酸在口腔鳞状细胞癌组织中的表达

目的 本研究旨在探讨透明质酸在不同分化口腔鳞状细胞癌中的表达及意义.方法 应用免疫组织化学法检测37例不同分化程度口腔鳞状细胞癌组织中透明质酸的表达.结果 按阴性(-)、弱阳性( )、阳性( )、强阳性( )表示,并进行统计学分析.结果 透明质酸主要表达于肿瘤间质和细胞外基质,细胞膜和胞浆中染色相对较少.37例口腔鳞状细胞癌组织中,低分化鳞癌透明质酸的表达明显高于高分化鳞癌(P＜0.05),表达随肿瘤分化程度降低而增强.结论 透明质酸的表达与口腔鳞状细胞癌的分化程度有关,分化越低,其表达越强.透明质酸的高表达可能有利于病变的侵袭和转移.     

Smad7蛋白在口腔鳞癌组织中的表达及其对口腔鳞癌细胞增殖和迁移能力的影响

目的：检测Smad7蛋白在口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）中的表达及临床意义,探讨其在口腔鳞癌细胞增殖和迁移中的作用。方法：利用免疫组织化学染色,检测31例原发性口腔鳞癌患者肿瘤组织及癌旁标本中Smad7的表达,并分析其与淋巴结转移之间的关系;利用CCK-8及细胞划痕实验检测Smad7基因沉默对肿瘤细胞增殖及迁移能力的影响;通过Smad7 siRNA干扰HN4细胞,影响Smad7蛋白的表达,利用免疫印迹及qRT-PCR检测其对上皮-间充质转化（epithelial- mesenchymal transition,EMT）相关指标蛋白及RNA表达的影响。采用SPSS18.0软件包对数据进行统计学分析。结果：在口腔鳞癌肿瘤组织中,Smad7蛋白在细胞核和细胞质的表达均显著高于对应的癌旁组织。Smad7的表达与患者颈淋巴结转移显著相关。Smad7 siRNA干扰HN4细胞后,细胞的增殖能力减弱,迁移能力增强。Smad7 siRNA干扰使得HN4细胞神经钙黏附素（N-cadherin）蛋白的表达量升高,而上皮钙黏蛋白（E-cadherin）的表达量下降,N-cadherin蛋白及波形蛋白（Vimentin）RNA表达量显著升高,与对照组相比有显著差异。结论：Smad7的表达与口腔鳞癌患者颈淋巴结转移相关,且Smad7在口腔鳞癌肿瘤细胞的增殖及侵袭转移中发挥重要作用。     

Aberrant expression of beta- and gamma-catenin is an independent prognostic marker in oral squamous cell carcinoma

Alteration in expression of E-cadherin and catenins is associated with loss of differentiation, acquisition of an invasive phenotype and poor clinical outcome in many types of cancer. To identify molecular prognostic markers, membrane expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated immunohistochemically in relation to preoperative tumour-related features, clinical course and prognostic value, and were found to be significantly correlated with an endophytic growth pattern and pathologically proved lymph-node metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma-catenin was also significantly correlated with poor disease-specific 5-year survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox proportional hazard regression analysis showed that alteration of beta- and gamma-catenin expression was a significantly independent prognostic parameter for survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic growth pattern and advanced N-category. These results indicate that patients with OSCC and absent or reduced membrane expression of beta- and gamma-catenin should be considered a high-risk group for regional lymph-node metastasis and poor prognosis.     

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。     

Hippo信号通路在口腔鳞状细胞癌中的研究进展

口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）是由口腔上皮细胞发展而来的一种常见癌症,具有高患病率、高死亡率和高致畸率的特点,严重威胁人们的生命健康。Hippo信号通路在肿瘤发生、干细胞稳态的调控、组织再生以及器官大小的控制方面起着关键作用。在OSCC中,激活Hippo通路信号可抑...     

Association of the infiltration of tumor-associated macrophages,expression of Smad7 protein and prognosis in oral squamous cell carcinoma

ObjectiveTo explore the association between Smad7 expression and tumor-associated macrophage (TAM), and their relationship with clinicopathological features and prognosis in patients with oral squamous cell carcinoma (OSCC).MethodsThis study collected cancer tissues from 314 OSCC patients from May 2002 to May 2012 at our hospital. Immunohistochemistry was carried out to detect the density of CD68⁺ cells and Smad7.ResultsThe densities of CD68TF_Mean and CD68TF_Hotspot shared a significant negative correlation with the immunoscore (IS) of Smad7, indicated that Smad7 was evidently increased with the decrease densities of CD68TF_Mean and CD68TF_Hotspot in OSCC tissues. Besides, low differentiation degree together with high TNM, T and N stage of OSCC patients presented decreased densities of CD68TF_Mean and CD68TF_Hotspot but increased expression of Smad7. Kaplan-Meier univariate survival analysis showed that the prognosis of OSCC patients was associated with differentiation degree, clinical stages, Smad7 expression, as well as densities of CD68TF_Mean and CD68TF_Hotspot. Cox regression analysis results demonstrated that N staging, the densities of CD68TF_Mean and CD68TF_Hotspot and Smad7 expression were independent risk factors influencing the survival rate of OSCC patients.ConclusionDecreased densities of CD68TF_Mean and CD68TF_Hotspot were negatively correlated with the increased Smad7 expression in OSCC tissues, both of which linked to clinicopathological features and prognosis of OSCC.     

表皮生长因子受体在口腔扁平苔藓、口腔乳头瘤及口腔鳞状细胞癌中的表达

目的:研究表皮生长因子受体(epidermal growth factor receptor,EGFR)在口腔扁平苔藓(OLP)、口腔鳞状细胞乳头瘤(SCP)及口腔鳞状细胞癌(SCC)中的表达,探讨其在口腔黏膜炎症、增生及癌发生过程中的意义.方法:用免疫组化方法检测EGFR在20例口腔黏膜扁平苔藓(单纯增生10例,伴糜烂10例)、20例口腔乳头瘤、20例口腔鳞状细胞癌及5例正常口腔黏膜中的表达.采用Fromowitz法计数阳性细胞.应用SPSS11.5软件包分析EGFR在不同病变中的表达差异.结果:EGFR在非糜烂型扁平苔藓组主要表现为弱阳性表达;糜烂型扁平苔藓组强阳性表达率为20％;乳头瘤组的强阳性表达率为25％;鳞状细胞癌的强阳性表达率为60％.扁平苔藓糜烂组和非糜烂组之间EGFR强阳性表达率有显著差异(P＜0.05);糜烂组OLP与乳头瘤组的强阳性表达率无显著差异;口腔鳞癌组的强阳性表达率显著高于扁平苔藓组及乳头瘤组.结论:EGFR可能成为口腔鳞癌化学预防作用的重要靶点.     

鳞状细胞癌抗原(SCC-Ag)在口腔鳞癌患者血清中表达的临床意义

用化学发光法检测36例口腔鳞癌、11例口腔颌面部其他恶性肿瘤、45例口腔颌面部良性肿瘤患者以及70例正常人血清中鳞状细胞癌抗原(SCC-Ag)水平。鳞癌组SCC-Ag水平明显高于良性肿瘤组(P<0.01)、正常组(P<0.01)以及其他恶性肿瘤组(P<0.05)。SCC-Ag可作为口腔鳞癌患者辅助诊断指标。     

口腔疣状癌与口腔鳞状细胞癌差异基因表达的对比分析

目的研究口腔疣状癌与口腔鳞癌组织基因的差异表达，探讨口腔疣状癌（oral Verrucous carcinoma，OVC）与口腔鳞癌（oral squamous cell carcinoma，OSCC）的基因学基础。方法应用cDNA芯片技术对4例OVC和4例OSCC组织mRNA检测，通过芯片杂交、生物信息学处理，找出两者间差异表达基因。结果BioStarH-40芯片发现差异表达基因593条，差异表达基因占15．2％，其中表达增强283条（显著增强59条），表达降低310条（显著降低98条）。结论OVC与OSCC基因表达比较，差异有统计学意义，这些差异可能在各自不同的生物学行为中起重要作用。     

Midkine expression in oral squamous cell carcinoma and leukoplakia

J Oral Pathol Med (2012) 41 : 21–26 Background: Midkine (MK), a 13‐kDa heparin‐binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control). Methods: Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki‐67, PCNA, p53, bcl‐2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK⁺ cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated. Results: The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late‐stage tumors (T3/T4) compared with early‐stage lesions (T1/T2). MK‐positive lesions also showed increased expression of the anti‐apoptotic protein bcl‐2. Conclusion: OCSCC, particularly late‐stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti‐apoptotic genes, as shown by the augmented bcl‐2 positivity in MK‐positive tumors.     

CXCR4、P-Akt在口腔鳞状细胞癌组织中表达的研究

目的：观察口腔鳞状细胞癌（OSCC）组织中CXCR4、P-Akt的表达与分布,了解CXCR4、P-Akt与OSCC恶性表现的关系。方法：应用免疫组织化学SP法对实验组30例OSCC组织标本和对照组10例正常口腔黏膜组织标本中的CXCR4、P-Akt的表达进行检测,应用计算机辅助图像分析仪对表达结果进行图像分析,然后进行统计学分析。结果：①CXCR4、P-Akt在OSCC组织中呈强阳性表达,且CXCR4、P-Akt蛋白表达水平显著高于对照组（P〈0.01）;②OSCC分化程度高的癌组织CXCR4、P-Akt蛋白表达水平显著低于分化程度低的癌组织（P〈0.05）,CXCR4、P-Akt蛋白表达水平在淋巴结转移组较无淋巴结转移组明显升高（P〈0.05）。结论：CXCR4、P-Akt在OSCC组织中的高表达,其表达水平与OSCC的病理分化程度及淋巴结转移有关。     

P-糖蛋白在口腔癌中的表达研究

目的　探讨口腔癌细胞P -糖蛋白表达的程度及其与化疗疗效的关系。方法　以JSB - 1为Ⅰ抗采用免疫组化方法对 2 8例口腔癌患者的化疗前后共 56例标本进行研究。结果　在 2 8例化疗前标本中 ,1 3例表达P -gp阳性 ,占46 .4% ,而化疗后有 1 7例表达阳性 ,占 60 .7% ,无统计意义。根据化疗效果分组 ,有效组 1 1例中只有 4例P -gp表达阳性 ,而无效组 1 7例中则有 1 0例表达P -gp阳性 ,前者占36 .4% ,后者占 58.8% ,二者之间无显著性差异。结论　P - gp在口腔癌中的表达较高 ,且化疗后表达较化疗前高 ,提示了部分口腔癌患者化疗效果不佳可能与之有关     

肿瘤转移蛋白Ezrin在口腔鳞状细胞癌中的表达

目的检测Ezrin在口腔鳞状细胞癌(OSCC)、癌旁组织和口腔正常组织中的表达,探讨其在OSCC的发生发展过程中的作用及其与肿瘤淋巴结转移的关系。方法采用免疫组织化学方法检测未接受放疗和化疗的OSCC患者的手术切除标本50例、癌旁组织标本15例及口腔正常组织标本15例,用鼠抗人Ezrin单克隆抗体以及SP超敏试剂盒进行染色,采用半定量积分法判断结果,进行统计学分析,得出结论。结果 1)在口腔正常组织、癌旁组织和OSCC中,Ezrin表达分别为26.67%、53.34%、78.00%,其差异具有统计学意义(P<0.05)。2)Ezrin在口腔正常组织、癌旁组织和OSCC中表达逐渐增高,其在癌旁组织和正常组织、OSCC和癌旁组织、OSCC和正常组织之间的表达差异具有统计学意义(P<0.05)。3)Ezrin的表达与肿瘤淋巴结转移相关(P<0.05),与细胞分化程度无关(P>0.05)。结论 1)Ezrin在OSCC的发生发展过程中可能起着重要作用。2)检测OSCC组织中Ezrin的表达水平可能有助于对OSCC是否具有淋巴结转移潜能进行预测。3)OSCC中Ezrin的表达与肿瘤淋巴结转移有关、与组织病理学分级无关。     

Pharmacodiagnostic evaluation of EGFR expression in oral squamous cell carcinoma

OBJECTIVE: To determine epidermal growth factor receptor (EGFR) expression in oral squamous cell carcinomas (OSCC), and its possible relationships with clinical findings, histological findings, disease course and prognosis. MATERIALS AND METHODS: Surgical specimens of 47 OSCCs were studied immunohistochemically for detection of EGFR using a standardized immunohistochemical detection system (EGFR PharmaDx kit). Statistical analysis was used to investigate possible relationships between EGFR expression and clinical findings, histological findings, cell proliferation (MIB1 labelling index), disease course and patient survival. RESULTS: Epidermal growth factor receptor expression was absent or weak in 12 cases (25.5%) and moderate or intense in 35 cases (74.5%). However, EGFR expression did not show statistically significant associations with any of the clinical, histological, biological or prognostic variables considered. CONCLUSION: First, despite previous suggestions that EGFR is a useful indicator of biological tumour behaviour, the present results suggest that EGFR is not a useful indicator of prognosis in OSCC. Secondly, the high prevalence of EGFR overexpression suggests that the possibility of anti-EGFR therapy in OSCC merits further investigation.     

Increased expression of Cathepsin B in oral squamous cell carcinoma

Previously, an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC) was established with a line of human immortalized oral epithelial cells (HIOECs), a line of cancerous HB96 cells and another type of cell (HB56 cells) at the early stage of carcinogenesis. In this study, comparative proteomic analysis identified a panel of differentially expressed proteins among these cells. Cathepsin B was one of the significantly up-regulated proteins accompanying cellular transformation. Cathepsin B was further validated for its expression in the three cell lines and in clinical samples of tumour tissues and their adjacent normal epithelia from 30 primary OSCC patients. Western blot analysis and real-time PCR detected increased Cathepsin B protein and mRNA levels in the cancerous HB56 and HB96 cells over HIOECs. Immunohistochemistry and real-time PCR showed elevated Cathepsin B protein and mRNA levels in the tumour tissues over the adjacent non-malignant epithelia from OSCC patients. The results presented here suggest that the expression of Cathepsin B increases along with the cancerisation in OSCC both in vitro and in vivo, and it may serve as a candidate biomarker of OSCC.