口腔鳞癌组织中P15和P21的表达研究

目的探讨p15和p21基因的蛋白产物在口腔鳞癌中的表达及意义。方法采用免疫组化P—V法检测108例口腔鳞癌和10例正常口腔黏膜组织中P15和P21蛋白的表达，并将结果进行统计分析。结果口腔鳞癌组织中P15蛋白的阳性表达率低于正常口腔黏膜组织（P〈0．05），而P21蛋白的阳性表达率两组间无明显差异（P〉0．05）；口腔鳞癌中，Ⅲ、Ⅳ期口腔鳞癌P15蛋白的阳性表达率明显低于Ⅰ、Ⅱ期口腔鳞癌的表达率（P〈0．01），无颈淋巴结转移组P15蛋白表达水平比有转移组高（P〈0．05）；P21阳性表达率在不同性别组中的表达差异具有统计学意义（P〈0．05）。结论P15蛋白的表达与口腔鳞癌的临床分期及淋巴结转移有关，P15蛋白表达水平可作为临床评估口腔鳞癌恶性程度、转移和预后的参考指标。     

卵巢上皮性肿瘤中Skp2、p27kipl、E-cad的表达

目的检测Skp2、p27kipl和E-cad在卵巢上皮性肿瘤中的表达情况及其相互关系。方法采用免疫组化SP法，检测99例卵巢上皮性肿瘤组织中Skp2、p27kipl及E-cad的表达。结果p27kipl在卵巢良性肿瘤、交界性肿瘤的表达率分别为76．5％、70．6％高于卵巢癌29．2％（P〈0．05），在早期癌中的表达高于晚期癌（P〈0．05）。Skp2在卵巢良性肿瘤、交界性肿瘤的表达率分别为0、23．5％，均低于卵巢癌50．8％（P〈0．05），在早期癌的表达低于晚期癌（P〈0．05）。卵巢癌中skp2表达与组织分化有关，在低分化癌的阳性表达率高于高分化癌（P〈0．05），在组织学类型方面，浆液性癌中skp2的阳性表达率高于非浆液性癌（P〈0．05）。E—cad在良性肿瘤、交界性肿瘤和卵巢癌表达率分别为88．2％、82．4％、55．4％，恶性组低于良性组（P〈0．05）。E—cad在早期癌的表达率高于晚期癌（P〈0．05）。Skp2表达与p27kipl表达呈负相关（P〈0．05），E-cad表达与p27kipl表达呈正相关（P〈0．05），而E-cad表达与Skp2表达则呈负相关（P〈0．05）。结论skp2过度表达与p27kipl表达减少可能与卵巢上皮性肿瘤的发生发展密切相关，而E-cad在晚期卵巢癌中表达降低可能反映了卵巢癌分化程度的降低。     

转录因子Snail及黏附分子E-cadherin在胃癌中的表达及意义

目的探讨转录因子Snail及黏附分子E—cadherin在胃癌中的表达及意义。方法采用免疫组化sP法检测96例胃癌组织和80例癌旁组织中Snail、E—cadherin的表达，分析两者在不同组织类型与分化程度胃癌中的表达，以及与临床病理因素之间的关系。结果胃癌组织E—cadherin的阳性率（37．5％）显著低于癌旁组织（100％）（P〈0．05），E—cadherin的表达与胃癌不同分化程度、组织学类型、浸润深度、淋巴结转移、临床分期及远处转移有关（P〈0．05）。胃癌组织Snail阳性率（83．3％）显著高于癌旁组织（41．25％）（P〈0．05），Snail的表达与胃癌不同分化程度、组织学类型、浸润深度、淋巴结转移及远处转移有关（P〈0．05）。胃癌组织中E—cadherin与Snail的表达呈负相关（P〈0．05）。结论E—cadherin蛋白低表达与Snail蛋白高表达可能是胃黏膜恶性转变以及胃癌发生浸润转移的重要生物学标志。联合检测E—cadherin及Snail对预测胃癌浸润转移有重要意义。     

上皮型钙黏附蛋白、CD44v6及连接蛋白43在肝细胞癌中的表达及意义

目的研究上皮型钙黏附蛋白（E-cad）、CD44v6和连接蛋白43（Cx43）在人肝细胞癌（HCC）中的表达及其表达与患者性别、年龄和组织学分级的关系。方法采用免疫荧光双标记染色技术结合激光扫描共聚焦显微镜观察E—cad、CD44v6及Cx43在30例正常肝组织,25例肝良性病变和38例HCC中的表达;另在HCC组检测并分析了该3种标记物的表达与性别、年龄和组织学分级的关系。结果E—cad与Cx43均在正常肝组织及肝良性病变组高表达,而在HCC组表达都明显降低,前两组与HCC组问表达强度差异均有统计学意义（FE-cad=879．2,F Cx43=303．7,P〈0．05）。相反,CD44v6在正常肝组织及肝良性病变组表达较低,而在HCC中表达较高,差异有统计学意义（F=2057．2,P〈0．05）。HCC组E—cad和Cx43阳性表达强度在患者不同性别、年龄及肿瘤的组织学分级问的差异均无统计学意义（P〉0．05）;而CD44v6表达与HCC的组织学分级有关,HCC分化差,CD44v6表达高（t=-2．06,P〈0．05）,但不同年龄、性别组HCC的CD44v6阳性表达强度差异无统计学意义（P〉0．05）。HCC组E—cad与Cx43的表达呈正相关,而E—cad、Cx43与CD44v6的表达呈负相关。结论HCC的发生、发展伴随着多种分子表型的改变。E—cad、Cx43的低表达与CD44v6的高表达可能参与HCC的侵袭,尤其是CD44v6的表达还与HCC的组织学分级相关。三者联合检测对判断HCC的诊断和预后有一定价值。     

E-cadherin、β-catenin、CD44v6在乳腺癌中的表达

目的　探讨乳腺癌中E cadherin(E cad)、β catenin(β cat)、CD4 4v6蛋白表达。 方法　采用免疫组化S P法测定 4 8例乳腺癌中E cad、β cat、CD4 4v6蛋白的表达。 结果　E cad、β cat蛋白的表达强度 ,无淋巴结转移组高于有淋巴结转移组 (P <0 0 5 ) ,与肿瘤的大小、病理分级、组织学分类无关 ;在乳腺癌中随着E cad强度的增加 ,β cat阳性率亦呈上升趋势 (P <0 0 5 )。CD4 4v6蛋白的表达强度 ,有淋巴结转移组高于无淋巴结转移组 (P <0 0 5 ) ,与肿瘤的大小、病理分级、组织学分类无关。结论　E cad、β cat、CD4 4v6的表达可作为判断乳腺癌是否转移的可靠指标     

宫颈鳞癌和癌前病变中eIF-4E表达及其与HPV16/18感染的关系

目的探讨真核翻译启始因子eIF-4E在宫颈鳞癌和癌前病变中的表达规律及其与人乳头瘤病毒（HPV）感染之间的关系。方法采用免疫组化ABC法和原位杂交技术检测eIF-4E蛋白和HPV16／18DNA在10例正常宫颈鳞状上皮，29例低级别上皮内瘤变（CIN1级），31例高级别上皮内瘤变（CIN2、3级）和31例宫颈鳞癌中的表达。结果eIF4E在正常宫颈鳞状上皮中呈阴性表达，随着上皮病变级别升高，表达逐渐增强：低级别〈高级别上皮内瘤变〈宫颈鳞癌（P〈0．05），且在宫颈鳞癌中表达更强；HPV16／18DNA在四组中的阳性表达率，除高级别上皮内瘤变和宫颈鳞癌两组之间没有差别（均为96．8％）以外，其余各组之间差异均有显著性（P〈0．01）；在低级别、高级别上皮内瘤变和宫颈鳞癌三组中eIF-4E蛋白表达和HPV感染均呈明显正相关（P〈0．01）。结论宫颈鳞癌的发生与eIF-4E蛋白表达及HPV16／18感染密切相关；二者在宫颈鳞癌的发病机制中可能起着协同作用。     

E-钙黏蛋白、β-连环蛋白和Podoplanin在人胃腺癌中的表达及意义

目的：探讨E-钙黏蛋白（E—cadhefin）及β-连环蛋白（β-catenin）在人胃腺癌中的表达和在淋巴道转移中的作用。方法：取60例胃腺癌组织样本和30例正常组织,应用免疫组织化学方法观察E—Cad和β-Cat在人胃腺癌组织中的表达,应用Podoplanin标记淋巴管,检测胃腺癌组织中的微淋巴管密度（MLVD）。结果：60例胃腺癌组织中,E—Cad和β—Cat的表达与分化程度、淋巴结转移、TNM分期具有相关性,差异有统计学意义（P〈0．05）。E—cad的表达与肿瘤直径、浸润深度具有相关性,差异有统计学意义（P〈0．05）,而β-Cat的异常在这两组中无明显差异（P〉0．05）。Podoplanin只表达淋巴管,癌组织中的LMVD高于正常胃组织（P〈0．01）,癌周边缘区的LMVD高于肿瘤中心组织（P〈0．01）。LMVD的表达与分化程度、淋巴结转移、TNM分期具有相关性,差异有统计学意义（P〈0．05）。结论：E—Cad和β—Cat异常表达在胃腺癌进展中起重要作用,在淋巴转移过程中使肿瘤细胞进入淋巴导管起了一定促进作用。     

EZH2蛋白在食管癌组织中的表达

目的观察EZH2蛋白在食管鳞癌和腺癌组织中的表达，探讨EZH2蛋白与侵袭、转移程度不同的食管鳞癌及不同病理分级、组织类型食管癌之间的关系。方法采用免疫组织化学染色法、免疫印迹法，分析检测食管癌标本中EZH2蛋白的表达。结果食管癌组织标本均高表达EZH2蛋白，阳性染色定位于细胞核；部分正常组织、癌旁组织也有弱阳性着色。免疫印迹分析表明，食管鳞癌组织EZH2蛋白的表达明显高于癌旁及正常黏膜组织（P〈0．01）。癌旁组织高于正常黏膜组织（P〈0．05）。浸润、转移性食管鳞癌EZH2蛋白表达明显上调，与未发生浸润、转移的相比，差异有显著性（P〈0．05）。高分化鳞癌EZH2蛋白表达低于中、低分化者；但食管腺癌则相反，高分化腺癌的表达高于中、低分化者。结论EZH2蛋白在食管癌高表达，并与其组织类型、侵袭和转移特性密切相关。     

食管鳞癌catenin、E-cadherin和cyclinD1的表达及意义

目的：研究食管鳞状细胞癌中细胞周期素D1（cyclinD1)、钙粘附蛋白（E－cadherin,E-cad)、连接蛋白（cat)α，β，γ的表达及临床病理学意义。方法：采用免疫组织化学法检测62例食管癌手术标本的cyclinD1、E-cad、α-cat、β-cat、γ-cat蛋白表达，并结合临床随访资料进行分析。结果：cyclinD1、E-cad、α-cat、β-cat、γ-cat阳性病例分别为35例（56．5％）、39例（62．9％）、49例（79％）、59例（95．2％）和47例（75．8％）。其中α-cat与β-cat、E-cad蛋白表达呈正相关性，其相关系数分别为0．274和0．279（P＜0．05）。γ-cat蛋白缺失表达与淋巴结转移有显著相关性（P＜0．05）；E-cat、γ-cat蛋白缺失与保留表达和肿瘤分化程度、术后生存期长期，在统计学上有差异（P＜0．05）。结论：E-cat、γ-cat缺失表达是食管癌预后差的因素之一。     

兔肝VX2移植瘤模型中血清和转移肿瘤组织S100A6蛋白表达的动态变化

目的探讨兔肝VX2移植瘤模型建立和肿瘤发展过程中血清及瘤组织S100A6蛋白表达的动态变化,为阐明其在肿瘤发展过程中的作用积累实验依据。方法建立兔肝VX2移植瘤模型,观察期自接种第7天至第29天。ELISA法检测血清中S100A6的水平,SP免疫组织化学法检测组织中S100A6的表达。结果大体和病理检查证实模型建立成功,成功率为100％（49／49）。ELISA检测发现,对照组的血清S100A6均值为（4．09±0．20）ng／mL;荷瘤组各观测点的S100A6水平均低于对照组,第17、19、21、23、25、27、29天依次较对照组减少37．6％、79．9％、89．9％、92．9％、98．3％、98．5％和99．O％,差异显著（P〈0．05）,且减少趋势也具显著性（P〈0．05）。在各转移癌灶中,S100A6的表达也随荷瘤进程进行性降低趋势（P〈0．01）。结论在兔肝VX2移植瘤模型的肿瘤发展过程中,兔血清和肿瘤组织中S100A6的表达均呈进行性降低。提示S100A6蛋白血清含量可能成为肝癌分期和是否转移的标志物;恢复S100A6的表达可能对兔肝VX2移植瘤的发展和转移产生重要作用。     

ANO1在口腔鳞癌中的表达及临床分析

 目的 探讨ANO1基因及蛋白在口腔鳞癌中的表达及其临床意义。方法 应用免疫组化SP法及Northern blot检测81例口腔鳞癌组织及相应正常组织的ANO1基因及蛋白的表达进行检测,并结合临床病理资料和基因蛋白表达特征对比作差异显著性检验及相关分析。利用western blot检测ANO1在多株鳞癌细胞株的表达。结果 ANO1在口腔鳞癌组织中的阳性表达明显高于正常组织,有显著性差异( P <0.05);有淋巴结转移的口腔鳞癌组织ANO1阳性表达高于无转移的口腔鳞癌组织。有显著性差异( P <0.05);随着口腔鳞癌临床分期的升高,ANO1的阳性表达率升高(P＜0.05);而ANO1的阳性表达率与病理分级,年龄和性别暂无关(P＞0.05)。Hep-2的内源性ANO1表达最低, 而SCC-25细胞株的内源性ANO1表达最高。 结论 ANO1可能在口腔鳞癌的发生和进展过程中起到重要作用。     

表皮生长因子受体在口腔鳞癌组织中的表达及意义

目的：研究表皮生长因子受体（ＥＧＦＲ）在口腔鳞癌组织中的表达及其临床病理学意义。方法：采用免疫组化Ｓ－Ｐ法对６５例不同分化的口腔鳞癌组织及１０例正常口腔粘膜组织进行ＥＧＦＲ检测。结果：ＥＧＦＲ在鳞癌组织中呈异质性表达,其阳性率（６１．５％）明显高于正常口腔粘膜组织（Ｐ〈０．０１）;ＥＧＦＲ表达状况与鳞癌组织学分级,区域淋巴结转移及患者预后间存在相关关系（Ｐ〈０．０１或０．０５）。结论：ＥＧＦＲ在口     

High expression of ALDH1 and SOX2 diffuse staining pattern of oral squamous cell carcinomas correlates to lymph node metastasis

One of the major factors involved in the prognosis of oral squamous cell carcinoma (OSCC) patients is metastasis. Recent progress in cancer stem‐like cell/cancer‐initiating cell (CSC/CIC) research indicates that CSCs are related to metastasis. Aldehyde dehydrogenase 1 – (ALDH1) and SRY‐related HMG‐box gene 2 (SOX2) have recently been shown to be putative CSC markers for several human malignancies. The aim of this study was to determine the association of ALDH1 and SOX2 expression in oral squamous cell carcinoma (OSCC) with lymph node metastasis. Immunohistochemical staining of ALDH1, SOX2 and Ki67 was performed in 80 OSCC tissues. High expression rates of ALDH1 (2%–40%) were found to be related to lymph node metastasis (P = 0.0017). Interestingly, we found that SOX2 staining could be classified into two patterns: (i) peripheral staining pattern; and (ii) diffuse staining pattern. The diffuse staining pattern showed a significant correlation with lymph node metastasis (P < 0.001). No correlation was found between Ki67 staining and lymph node metastasis (P = 0.4724). The ALDH1 positive staining rates in metastatic lymph nodes were higher than that in corresponding primary OSCC tissues. These results indicate that high expression rates of ALDH1 and SOX2 diffuse staining patterns might be novel prediction markers for OSCC lymph node metastasis.     

Expression of E-cadherin and vimentin in oral squamous cell carcinoma

The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P < 0.05); E-cadherin expression was also significantly associated with tumor stage (P < 0.05); there are significantly difference between infiltrative margin and central area in patients with oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P < 0.05). E-cadherin and vimentin positive expression was associated with tumor metastasis of oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome.     

Expression of fascin in oral and oropharyngeal squamous cell carcinomas has prognostic significance - a tissue microarray study of 129 cases

AIMS: To elucidate the role of fascin in oral and oropharyngeal squamous cell carcinoma (OSCC) by correlation with clinical parameters. METHODS AND RESULTS: Paraffin sections using tissue microarrays of 129 patients with OSCC were investigated immunohistochemically. Fascin protein was overexpressed in OSCC cells compared with their non-neoplastic epithelial counterparts. For evaluating the intensity of fascin, 39 (30.2%) were classified as weakly immunoreactive, 76 (58.9%) as moderate reactive and 14 (10.9%) as intensely reactive. For evaluating the distribution of fascin, 64 (49.6%) were classified as < 55% and 65 (50.4%) were classified as >/= 55%. Fascin protein expression was correlated with size or extent of the tumour (P < 0.001), positive lymph node metastasis (P < 0.001), distant metastasis (P = 0.014) and clinical staging (P < 0.001). The immunoreactivity scores of fascin in OSCC were variable but showed significant correlation with histological grade, clinical TNM system and stage. CONCLUSION: Expression of fascin protein may play an important role in progression of OSCC. Overexpression of fascin contributes to a more aggressive clinical course and suggests the potential of fascin as a new molecular target for therapeutic intervention.     

Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model

Activation of matrix metalloproteinase-2 (MMP-2) is a common event in head and neck squamous cell carcinoma. An OSC-19 cell line, derived from human oral squamous cell carcinoma and known to metastasize to cervical lymph nodes, was implanted into the lingual margin of mice. The effect of marimastat (BB-2516), a broad MMP inhibitor, on the suppression of regional cervical lymph node metastasis was evaluated with an orthotopic implantation nude mice model. Marimastat was given immediately after OSC-19 implantation and continuously administered by an osmotic pump. The mice were divided into three groups by marimastat dose; Group A; 0 mg/kg/day, Group B; 30 mg/kg/day, and Group C; 150 mg/kg/day. Twenty-one days after implantation, primary oral tumors and cervical lymph nodes were resected. Cervical lymph node status was microscopically examined. Activation of MMP-2 in primary oral tumor was examined by gelatin zymography. Both cervical lymph node metastasis and activation of MMP-2 were significantly suppressed in Group C (P<0.05). Moreover, the Group C mice had a significantly better survival than group A (P=0.0026). There was a significant difference between Group A and Group C in terms of proliferation of tumor cells by proliferating cell nuclear antigen immunostaining (P=0.0120). These results suggest a positive role for marimastat in the inhibition of MMP-2 activation and prevention of cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). Improvement of survival in patients with OSCC could be expected using adjuvant therapy with marimastat. This revised version was published online in July 2006 with corrections to the Cover Date.     

Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer

Aurora-B kinase is a chromosomal passenger protein and is essential for chromosome segregation and cytokinesis. Aurora-B overexpression in various cancer cells induces chromosomal number instability to produce multinuclearity and relates to metastasis. Here, we examined the expression of Aurora-B in oral squamous cell carcinoma (OSCC) to elucidate the relationship between Aurora-B expression and clinico-pathological findings by immunohistochemistry. Aurora-B expression was observed in normal oral squamous epithelia and OSCC cases, but the number of positive cells was significantly higher in OSCC than in normal squamous epithelium (p < 0.01). The labeling index of Aurora-B was significantly correlated with lymph node metastasis (p < 0.01) and histological grades of differentiation (p < 0.01). We also compared Aurora-B expression with Ki-67 expression and a positive correlation was found (p < 0.0001). Moreover, Aurora-B expression is significantly more frequent in multinuclear tumor cells than in total tumor cells. In summary, we found that Aurora-B expression was well correlated with cell proliferation, induction of multinuclear cells, histological differentiation, and metastasis in OSCC. These findings suggest that Aurora-B may be involved in tumor progression and that Aurora-B can be a new diagnostic and therapeutic target for OSCC.     

Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma

Chang Y‐C, Nieh S, Chen S‐F, Jao S‐W, Lin Y‐L & Fu E (2010) Histopathology 57, 295–303
Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma Aims: To test the validity of an invasive pattern grading score (IPGS) developed for oral squamous cell carcinoma (OSCC) as a prognostic indicator and to elucidate the relationship between the IPGS and clinical parameters. Methods and results: The IPGS was applied to a total of 153 cases of OSCC. There were significant correlations between IPGS and distant metastasis (P = 0.01) or recurrence (P = 0.001). However, there were no significant correlations between IPGS and gender, age, size or extent, location, status of lymph node metastasis, clinical staging, or histological grading. Cases of OSCC with higher IPGS were associated with poor patient survival (P < 0.001) and higher probability of tumour recurrence (P = 0.001). Intraobserver (κ = 0.74) and interobserver agreement (κ = 0.67) were very satisfactory. Conclusions: Our study confirms the validity of the IPGS, an indicator that is simple and easy to use. IPGS not only provides histological assessment of biological behaviour, but also offers an independent prognostic factor that may influence the treatment of OSCC.     

CD44v6和E-cadherin表达与结直肠癌浸润转移关系

目的　探讨CD44v6和E cadherin(E cad)蛋白表达与结直肠癌浸润转移的相关性。方法　应用免疫组织化学技术 ,检测 90例结直肠癌组织中CD44v6和E cad蛋白表达。结果　 90例结直肠癌中CD44v6和E cad蛋白阳性表达率分别为75 6 %和 46 7%。CD44v6高表达及E cad低表达与结直肠癌Dukes分期、浆膜浸润、淋巴结转移、肝脏转移均呈正相关 (P <0 0 5 )。结直肠癌中CD44v6表达与E cad表达呈负相关 (r =- 0 4 3,P <0 0 0 5 )。结论　CD44v6和E cad表达与结直肠癌浸润转移密切相关。检测CD44v6和E cad蛋白表达可作为判断结直肠癌预后的客观指标。