EphA2在涎腺肿瘤中的表达及其临床意义

目的检测EphA2在涎腺肿瘤中的表达，并分析其临床病理意义。方法免疫组化S-P法检测10例正常涎腺组织、30例多形性腺瘤、30例黏液表皮样癌（MEC）、30例腺样囊性癌（ACC）中EphA2的表达。分析EphA2表达与患者的年龄、性别、肿瘤部位、大小、TNM分期以及复发、淋巴结转移等临床病理因素的关系。比较EphA2在正常涎腺组织及几种常见的涎腺良、恶性肿瘤中的表达差异。结果EphA2在正常涎腺组织中主要表达于腺管上皮，而腺泡细胞几乎不表达。EphA2在正常涎腺组织、多形性腺瘤、涎腺癌（包括黏液表皮样癌和腺样囊性癌2组）中的表达依次增高，存在显著性差异（P〈0．05）。EphA2的表达与涎腺癌瘤体大小、TNM分期、复发和淋巴结转移有关（P〈0．05）。结论EphA2可能影响涎腺肿瘤发生、发展及其预后。     

正常和腺样囊性癌涎腺中赖氨酸18位点乙酰化组蛋白H3表达的研究

目的探讨赖氨酸18位点（lysine 18 site,lys18）乙酰化组蛋白H3（acetyl-histone H3）在涎腺腺样囊性癌（adenoid cystic carcinoma,ACC）和正常涎腺中表达的意义。方法免疫组织化学Envision二步法检测60例ACC和49例正常涎腺中lys18乙酰化组蛋白H3的表达,分析其与ACC发生部位、组织学分级、临床分期、神经侵犯等肿瘤临床病理特征的关系。结果正常涎腺中导管细胞、腺泡细胞以及ACC肿瘤细胞中均有lys18乙酰化组蛋白H3阳性表达,表达位于细胞核。但lys18乙酰化组蛋白H3在ACC中的表达显著低于正常涎腺（χ2=46.745,P=0.000 1）,且其表达与ACC的临床病理特征没有相关性（P〉0.05）。结论组蛋白H3 lys18低乙酰化可能与ACC的肿瘤发生有关。     

涎腺腺样囊性癌细胞株p16基因缺失、突变及表达意义

目的　研究 p16基因在涎腺腺样囊性癌细胞株中的缺失和突变等结构变化及其表达之间的关系。方法　应用聚合酶链反应 (PCR)和 PCR-单链构象多态性 (SSCP)对涎腺腺样囊性癌细胞株 ACC- 2和高转移细胞克隆 ACC- M进行 p16基因缺失、突变的检测 ,应用免疫组化方法检测 p16基因在细胞株中的蛋白表达。结果　涎腺腺样囊性癌细胞株 ACC- 2检测 p16基因阳性 ,高转移细胞克隆 ACC- M缺失 ,两个细胞克隆均无点突变 ,ACC- 2的p16蛋白表达阳性 ,而 ACC- M蛋白表达阴性。结论　 p16基因在高转移涎腺腺样囊性癌克隆中的缺失 ,表明 p16基因在涎腺腺样囊性癌的演进和转移中具有抑癌作用。     

Genistein对涎腺腺样囊性癌细胞生长及Survivin表达的影响

目的研究酪氨酸蛋白激酶抑制剂Genistein对人涎腺腺样囊性癌细胞株SACC- 83细胞增殖及Survivin表达的影响。方法以不同浓度Genistein作用于SACC- 83细胞不同时间后,用MTT法分析细胞的生长增殖,用流式细胞术检测细胞凋亡,用Western印迹分析及电泳凝胶成像分析软件定量检测Survivin的表达。结果Genistein对SACC-83细胞有一定的抗增殖作用,且当其作用到一定时间达到一定的浓度后,该作用与浓度及时间呈依赖关系;SACC- 83细胞经220 μmol/L Genistein作用3 d其生长明显受到抑制,并显著诱导细胞凋亡（P<0.01）,同时伴有抗凋亡蛋白Survivin的表达下调。结论Genistein能明显抑制人涎腺腺样囊性癌细胞株SACC- 83细胞生长并诱导凋亡;Survivin的表达减少可能是Genistein诱导凋亡的机制之一。     

涎腺腺样囊性癌组织中ILK和E-cadherin的表达及意义

目的:探讨整合素连接激酶(integrin-linked kinase,ILK)和上皮型钙黏蛋白(E-cadherin)在涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)组织中的表达及其意义。方法:采用免疫组织化学SP法检测ILK和E-cadherin在SACC及正常涎腺组织中的表达。结果:ILK在SACC中表达,ILK的表达与SACC临床病理分型不相关(P>0.05),与TNM分期有关,在发生神经侵犯及远处转移的病例中,ILK的表达明显增加(P<0.05);与正常涎腺组织相比,E-cadherin在SACC中表达下降,差异有统计学意义(P<0.05),E-cadherin表达与不同组织病理学类型有关,且在实体型、发生神经侵犯及远处转移的病例中,E-cadherin表达下降更明显(P<0.05);ILK与E-cadherin的表达呈负相关(r=-0.768,P<0.001)。结论:SACC组织中ILK表达上调而E-cadherin表达降低,有望成为临床判断涎腺腺样囊性癌恶性程度、评估预后的潜在指标。     

采用组织芯片技术检测正常涎腺及其肿瘤组织中Skp2、P27的表达

目的:检测S期激酶相关蛋白2(S-phase kinase-associated protein2,Skp2)和抑癌基因p27在涎腺正常与良恶性肿瘤组织的表达,并探讨其意义。方法:采用组织芯片技术及免疫组化SP法对70例涎腺正常与良恶性肿瘤组织中的Skp2和P27表达进行检测,并做统计学分析。结果:2种良性肿瘤即基底细胞腺瘤与多形性腺瘤之间及2种恶性肿瘤即腺样囊性癌与黏液表皮样癌之间,Skp2与P27表达无显著差异。正常涎腺与良性肿瘤组织的比较,仅Skp2的阳性率有显著性差异;正常涎腺与恶性肿瘤组织的比较及涎腺良性与恶性肿瘤组织的比较,Skp2与P27的阳性率均有显著性差异。结论:Skp2与P27的异常表达可能参与了涎腺肿瘤的发生发展。Skp2蛋白表达与靶蛋白P27蛋白降解增强有关。     

涎腺腺泡细胞癌中磷酸化Rb蛋白及p27表达的意义

目的：探讨涎腺腺泡细胞癌（SACC）中Rb蛋白的功能状况及p27表达的意义,探讨其在SACC发生及预后中的意义。方法：本研究采用免疫组织化学方法检测了18例SACC及10例正常见涎腺组织中总Rb、磷酸化Rb及p27的表达,对所得结果进行统计学分析。结果：总Rb蛋白及p27在SACC中的阳性表达率与正常对照组相比无显著性差异,但是在SACC中表达的主要是磷酸化Rb,尤其是丝氨酸795位点磷酸化的Rb蛋白。结论：Rb蛋白磷酸化所导致的抑癌功能丧失可能是SACC发生的重要机制。     

金属蛋白酶及其组织抑制剂在涎腺腺样囊性癌细胞株表达的分子生物学研究

为了研究金属蛋白酶（ｍｅｔａｌｏｐｒｏｔｅｉｎａｓｅ，ＭＭＰ）及其组织抑制剂（ｔｉｓｓｕｅｉｎｈｉｂｉｔｏｒｏｆｍｅｔａｌｏｐｒｏｔｅｉｎａｓｅ，ＴＩＭＰ）对涎腺腺样囊性癌细胞（ａｄｅｎｏｉｄｃｙｓｔｉｃｃａｒｃｉｎｏｍａ，ＡＣＣ）转移的影响，本研究应用斑点印迹杂交的分子生物学方法检测ＡＣＣ２细胞系及高转移细胞株ＡＣＣＭ中ＭＭＰ２、ＭＭＰ９和ＴＩＭＰ２的表达。结果显示ＭＭＰ２，ＭＭＰ９在ＡＣＣＭ表达较高，在ＡＣＣ２表达较低，而ＴＩＭＰ２在ＡＣＣ２表达较高，在ＡＣＣＭ表达较低，证实ＭＭＰ２，ＭＭＰ９促进转移的发生，而ＴＩＭＰ２则抑制转移的发生。提示ＭＭＰ与ＴＩＭＰ平衡关系可能是ＡＣＣ转移的关键机制之一。     

环氧合酶-2、Ki-67在涎腺基底细胞腺瘤和基底细胞腺癌中的表达及临床意义

目的:研究环氧合酶-2(Cox-2)及Ki-67在涎腺正常组织(normal salivary gland,NSG)、基底细胞腺瘤(basal celladenoma,BCA)和基底细胞腺癌(basal cell adenocarcinoma,BCC)中的表达及相关性,探讨其表达程度及在恶变中的相互关系。方法:采用免疫组化(PV6001二步法)检测NSG 11例、BCA18例、BCC 9例中Cox-2及Ki-67的表达情况;采用SPSS 12.0软件对实验数据进行分析。结果:Cox-2在NSG中表达与BCA、BCC的差异均有统计学意义(P<0.01);Ki-67在NSG与BCA表达差异无统计学意义(P>0.05),在NSG与BCC中的表达差异有统计学意义(P<0.01);Cox-2、Ki-67表达与BCA组织病理分型的差异无统计学意义(P>0.05);Cox-2在不同部位的BCA中表达差异有统计学意义(P<0.01);Ki-67在不同部位BCA中表达差异无统计学意义(P>0.05);Cox-2和Ki-67在BCA表达中呈负相关(P>0.05),rs=-0.21,而在BCC表达中呈正相关,rs=0.94,P<0.01。结论:Cox-2、Ki-67可能参与BCA、BCC的发生、发展过程;联合检测Cox-2和Ki-67有助于BCA、BCC的预后判断。     

涎腺腺样囊性癌中趋化因子4、整合素β1表达的意义

目的 检测涎腺腺样囊性癌（adenoid cystic carcinoma of salivary gland，ACCs）中趋化因子4（chemokine receptor 4，CXCR4）和整合素β1（Integrin β1）的表达水平，并分析与临床病理的关系。方法 应用免疫组化法检测78例ACCs中CXCR4、Integrin β1的表达，以肿瘤周围涎腺组织对照，分析二者与ACCs临床病理因素的关系。结果 CXCR4、Integrin β1在ACCs中的表达率分别为65．4％、70．0％，且呈高度正相关（P〈0．01）。二者均与ACCs临床分期、复发、和远处转移有关（P〈0．05），并且与预后关系密切（P〈0．05）。结论 CXCR4的表达与Integrin β1高度正相关；二者的异常高表达与远处转移关系密切，可视为影响ACCs预后的重要因素之一。     

Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias

BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers. METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index. RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia. CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.     

bFGF、FGFR1在唾液腺肿瘤和瘤旁组织中的表达

目的:探讨碱性成纤维细胞生长因子(bFGF)和成纤维细胞生长因子受体1(FGFR1)在唾液腺良、恶性肿瘤和瘤旁组织中的表达及意义.方法:利用免疫组织化学法检测了43例唾液腺良、恶性肿瘤和30例良性肿瘤瘤旁组织中bFGF和FGFR1的表达.结果:bFGF和FGFR1在唾液腺良、恶性肿瘤组织和瘤旁组织中的表达均具有显著性差异(p<0.05).结论:bFGF和FGFR1在唾液腺肿瘤的发生,发展过程中发挥了一定的作用.     

The adhesion molecules NCAM, HCAM, PECAM-1 and ICAM-1 in normal salivary gland tissues and salivary gland malignancies

BACKGROUND: Some malignant salivary gland tumors are known for their propensity to exhibit perineural invasion and vascular metastases. It was hypothesized that alterations in the expression of cell adhesion molecules are involved in these processes. METHODS: The expression and distribution of neural cell adhesion molecule (NCAM), HCAM (CD44), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) in normal salivary gland tissues and selected salivary gland malignancies, especially adenoid cystic carcinoma (AdCyCa) and polymorphous low-grade adenocarcinoma (PMLG), were determined immunohistochemically, and their influence on histologically demonstrated perineural invasion, vascular invasion, and tumor recurrence/patient death were investigated. RESULTS: NCAM, HCAM, and ICAM-1 were often found to be expressed by neoplastic cells, but no correlation to perineural invasion, tumor behavior, or patient prognosis was found. PECAM-1 was rarely and only focally expressed in three tumors, all of which were related to tumor metastases and patient death. CONCLUSIONS: Immunohistochemical demonstration of NCAM, HCAM, and ICAM-1 is not related to perineural invasion or tumor behavior. PECAM-1 expression was related to vascular invasion and poor patient prognosis in three cases.     

Immunohistochemical localization of CEA,EMA and keratin in salivary mucoepidermal carcinoma]

Localizations of CEA,EMA and keration in 19 cases of mucoepidermal carcinomas were investigated using the indirect immunoperoxidase technique.The results showed CEA was negative in normal salivary glands and showed faint reaction in glands near carcinoma tissue.Keratin and EMA were localized in some myoepithelial cells.The positive rates in carcinoma tissue were 78.9%,89.5% and 84.2%,respectively.The positive rates and staining intensity of CEA and EMA in carcinoma tissue gradually decreased with the decline of tumor differentitation,but that of keratin showed no variation.the author consider that CEA and EMA could become good indices in clinically diagnosing mucoepithelial carcinoma and determining tumor differentiation type cell in mucoepidermal carcinoma and have a potential to multiply express the tumor elements of epithelium and/or mesenchyma.     

Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas

PURPOSE: The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas.Study design Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody. RESULTS: Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells. CONCLUSIONS: P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.     

细胞角蛋白18、19在口腔鳞状细胞癌侵袭转移中表达的研究进展

<正>口腔癌占全身恶性肿瘤的3%～5%,其中以口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)最常见,其复发和转移是影响预后的重要因素。随着研究技术的发展和对微转移的深入研究表明,及时发     

Prognostic value of cyclin D1, p27, and p63 in oral leukoplakia

BACKGROUND: Studies on the expression of genes regulating cell proliferation and apoptosis are essential to help better understand the severity and possible malignant transformation of oral leukoplakia. METHODS: The characteristics of cyclin D1, p27, and p63 were investigated in this microscopic study, complementing our previous results with Ki67, p53, and the apoptosis index. Clinical and histologic as well as immunohistochemical studies were carried out on oral leukoplakia of 18 patients. Homogenous, or non-homogenous (nodular or speckled) and erythroleukoplakia were determined clinically. Pathologic classification was performed according to the degree of dysplasia. Immunoperoxidase reaction for cyclin D1, p27, and p63 was carried out on the biopsy specimens and the positivity of the reactions was calculated for 1000 epithelial cells. RESULTS: The expression of cyclin D1 increased in parallel with the severity of leukoplakia. The p27 index was 14-16% in homogenous and nodular leukoplakias but it was substantially lower to 1-2% in erythroleukoplakia. The p63 index was 10% in homogenous, 5% in nodular or speckled, but nearly 20% in erythroleukoplakia, on the average. CONCLUSION: These results suggest that the characteristic expression of cyclin D1, p27, and p63 in various forms of leukoplakia may be of prognostic value.     

HLA-DR antigens in normal, inflammatory, and neoplastic salivary glands

A monoclonal antibody to HLA-DR antigens that is reactive in formalin-fixed tissues was used with the immunoperoxidase method to evaluate 212 salivary gland lesions (normal, nonspecific, and autoimmune inflammatory, benign, and malignant tumors). Results of immunostaining showed that (1) intercalated ducts, myoepithelial cells, and acinous cells of normal salivary glands express HLA-DR antigens, (2) autoimmune salivary gland disease results in greater HLA-DR expression than that seen in nonspecific inflammatory lesions or normal glands, (3) stromal cells associated with benign and malignant salivary gland tumors express HLA-DR antigens, and (4) numerous benign and malignant salivary gland tumors express HLA-DR antigens. It was of interest that lymphocyte-rich Warthin's tumors displayed epithelial immunoreactivity, whereas oncocytomas devoid of a lymphocytic component were invariably negative. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is both a normal and an inducible phenomenon in salivary glands, salivary gland neoplasia, and the desmoplastic host response. There is no discriminatory role in the immunologic detection of HLA-DR for differential diagnosis of salivary gland tumors.