Paxillin在涎腺腺样囊性癌中的表达

目的：探讨Paxillin与涎腺腺样囊性癌（salivary adenoid cystic carcinoma,SACC）预后的关系。方法：采用免疫组化分析47例SACC的Paxillin表达,并统计学分析Paxillin与SACC病理学分型、临床分期、局部复发、远处转移和患者生存率的关系。结果：Paxillin表达与SACC病理学分型、局部复发和患者生存率无明显相关,而与临床分期和远处转移呈正相关关系（P〈0.05）。结论：结果提示Paxillin的过度表达在SACC中常见,其过度表达与信号传导通路的改变可能与SACC的细胞增殖及癌转移相关,从而促进SACC的远处转移;Paxillin可作为预后指标来预测SACC的远处转移,指导临床治疗。     

组织蛋白酶D在涎腺腺样囊性癌表达的研究

目的 探讨组织蛋白酶Ｄ（ｃａｔｈｅｐｓｉｎ－Ｄ,Ｃａｔｈ－Ｄ）与涎腺腺样囊性癌（ＳＡＣＣ）预后的关系。方法 采用免疫组织化学链亲和素法分析５２例ＳＡＣＣ的Ｃａｔｈ－Ｄ表达,并统计学分析Ｃａｔｈ－Ｄ与ＳＡＣＣ病理学分型、临床分期、局部复发、远处转移和患者生存率的关系。结果 Ｃａｔｈ－Ｄ表达与ＳＡＣＣ病理学分型、局部复发和患者生存率无明显相关（Ｐ〉０．０５）,而与临床分期和远处转移呈正相关关系（Ｐ〈０     

影响涎腺腺样囊性癌预后因素的探讨

目的：研究５０例涎腺腺样囊性癌（ｓａｌｉｖａｒｙａｄｅｎｏｉｄｃｙｓｔｉｃｃａｒｃｉｎｏｍａ，ＳＡＣＣ）患者的肿瘤部位、临床分期、组织学分型及肿瘤转移抑制基因ｎｍ２３、组织蛋白酶Ｄ（Ｃａｔｈｅｐｓｉｎ－Ｄ，Ｃａｔｈ－Ｄ）、金属硫因蛋白（ｍｅｔａｌｏｔｈｉｏｎｅｉｎ，ＭＴ）、增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）、肿瘤抑制基因ｐ５３的关系。方法：用免疫组织化学反应进行多因素分析，探讨它们与局部复发、远处转移和生存率的关系。结果：影响ＳＡＣＣ局部复发的因素太多，以上各指标均不能独立判断ＳＡＣＣ的局部复发情况；ｎｍ２３和Ｃａｔｈ－Ｄ与ＳＡＣＣ远处转移有明显相关性（Ｐ＜０．０５），表明ｎｍ２３和Ｃａｔｈ－Ｄ在ＳＡＣＣ远处转移中具有重要作用，是预测ＳＡＣＣ远处转移的两项独立指标；临床分期与ＳＡＣＣ患者的生存率有明显相关性（Ｐ＜０．０５）。结论：临床分期可作为一项独立作用的指标来评价ＳＡＣＣ患者的预后。     

肿瘤转移抑制基因nm23在涎腺腺样囊性癌表达的研究

目的：探讨肿瘤转移抑制基因nm23与涎腺腺样囊性癌（salivary adenoid cystic carcinoma,SACC)预后的关系。方法：采用免疫组织化学链亲和素法分析52例SACC的nm23表达,并分析nm23与SACC病理学分型、临床分期、局部复发、远处转移和患者生存率的关系。结果：nm23表达与SACC病理学分型、临床分期、局部复发和患者生存率无明显相关（P＞0．05）,而与远处转移呈高度负相关关系（P＜0．01）。结论：nm23能抑制SACC远处转移的发生,并可作为预后指标来预测SACC的远处转移,指导临床治疗。     

桩蛋白在涎腺黏液表皮样癌中的表达

目的:探讨桩蛋白(paxillin)在涎腺黏液表皮样癌中表达的意义。方法:采用HE染色方法筛选典型病例与免疫组织化学方法分析21例黏液表皮样癌中paxillin的表达。结果:paxillin在正常涎腺组织的基底膜、腺管部位有弱阳性表达,在黏液表皮样癌中有强阳性表达,其强弱程度与病理分级存在相关性(r=0.75,P<0.01),染色强度与染色面积评分之和与病理分级存在相关性(r=0.93,P<0.01),在肿瘤浸润前沿表达显著。结论:在涎腺黏液表皮样癌中paxillin表达强弱程度与病理分级密切联系,癌症浸润前沿表达情况可以为临床治疗提供参考。     

肿瘤转移抑制基因BRMS1 mRNA在口腔鳞癌中的表达及临床意义

目的:研究肿瘤转移抑制基因-乳腺癌转移抑制基因(breast cancer metastasis suppressor 1,BRMS1)在口腔鳞癌组织及癌旁组织中的表达,并探讨其表达规律及与临床病理学关系。方法:用RT-PCR技术检测38份口腔鳞癌、20份癌旁正常组织的BRMS1 mRNA的表达情况,并结合肿瘤病人的临床病理学资料进行分析。结果:口腔鳞癌组织BRMS1 mRNA表达量比癌旁组织明显偏低,其差异具有统计学意义(P<0.05)。BRMS1 mRNA表达水平在转移病例明显低于非转移的病例,低分化标本明显低于高中分化标本,差异均有统计学意义(P<0.05);但是在肿瘤临床分期、性别、年龄、瘤体大小等之间的表达量比较,差异均无统计学意义(P>0.05)。结论:BRMS1在口腔鳞癌中的表达水平跟肿瘤的转移密切相关,也跟肿瘤的组织分化程度有关,可以作为口腔鳞癌治疗的预后指标之一。     

整合素连接激酶和基质金属蛋白酶-9在涎腺腺样囊性癌中的表达及意义

目的: 探讨整合素连接激酶(ILK)和基质金属蛋白酶-9(MMP-9)在涎腺腺样囊性癌(SACC)中的表达及意义。方法: 选取59例SACC患者和42例非肿瘤患者正常涎腺组织,利用qRT-PCR技术检测ILK和MMP-9在SACC组织中表达。结果: SACC组织中ILK mRNA和MMP-9 mRNA相对表达量均高于对照组,差异均有统计学意义(P<0.05);ILK和MMP-9在SACC组织中表达均与组织类型、淋巴结转移、TNM分期有关(P<0.05),实体型和管状型SACC组织中ILK mRNA和MMP-9 mRNA相对表达量均高于筛状型(P<0.05);Pearson相关分析显示,SACC组织中ILK mRNA相对表达量与MMP-9 mRNA相对表达量呈正相关(r=0.586,P=0.000)。结论: ILK和MMP-9在SACC组织中呈高表达,可能共同协同参与了肿瘤细胞侵袭、转移过程。     

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。     

中期因子和微血管密度在涎腺腺样囊性癌组织中的表达

目的探讨中期因子（MK）、微血管密度（MVD）在涎腺腺样囊性癌（SACC）组织中的表达和意义,以及两者之间表达的相关性。方法 采用免疫组织化学方法（SP法）检测60例SACC组织及26例正常涎腺组织中MK、MVD的表达状况及两者之间的相关性。结果 MK在SACC组织中高表达,阳性表达率为70.0%（42/60）,正常组织中未见MK表达,二者间差异有统计学意义（P<0.05）。SACC中MVD计数为38.73±8.96,正常涎腺组织中MVD计数为11.15±3.33,二者间差异有统计学意义（P<0.05）。MK、MVD的表达与年龄、性别、分型无关（P>0.05）;与肿瘤的大小、淋巴结转移、TNM分期有关（P<0.05）。MK和MVD在SACC中的表达具有正相关性（r=0.560,P<0.05）。结论MK蛋白的表达、MVD计数的增加与SACC的发生有关,可能是SACC早期诊断指标之一。     

金属硫因蛋白、增殖细胞核抗原和肿瘤抑制基因p53在涎腺腺样囊性癌表达的研究

本研究对金属硫因蛋白(metallothionein,MT)、增殖细胞核 抗原(proliferating cell nuclearantigen,PCNA)和肿瘤抑制基因p53与涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)患者预后之间的关系进行了研究。通过对50例SACC的MT、PCNA与p53免疫组织化学反应及临床资料分析,结果表明:MT的表达与SACC患者生存率明显相关(P<0.05),它能在一定程度上判断SACC患者的预后情况;PCNA是评价细胞增殖状态的指标,PCNA的表达与SACC远处转移存在明显相关(P<0.05),肿瘤细胞增殖能促进SACC的远处转移;p53基因在SACC的发生发展过程中的作用不明显,可能存在其它某种或多种基因发挥更重要的作用。     

MAPK、MMP-2和MMP-9在唾液腺腺样囊性癌中的表达及临床意义

目的:研究人唾液腺腺样囊性癌组织中MAPK(p-ERK1/2、p-P38及p-JNK)、MMP-2和MMP-9的表达情况,探讨其与临床病理特征的关系.方法:应用免疫组织化学SP法检测27例腺样囊性癌组织标本(癌组)和15例正常唾液腺组织标本(对照组)中p-ERK1/2、P-P38、p-JNK、MMP-2和MMP-9的表达情况.采用SPSS17.0软件包对数据进行统计学分析.结果:p-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9在腺样囊性癌组中的阳性表达率(分别为81.48%、88.89%、70.37%、81.49%和77.78%)均显著高于在正常唾液腺对照组中的阳性表达率(分别为20%、26.67%、26.67%、26.67%和26.67%),差异有统计学意义(分别为P<0,01、P<0.01、P<0.05、P<0.01和P<0.01).腺样囊性癌组织中p-ERK1/2、p-P38、MMP-2和MMP-9在Ⅲ～Ⅳ期组的阳性表达率(分别为88.89%、100%、94.44%和94.44%)显著高于Ⅰ一Ⅱ期组(分别为44.44%、66.67%、55.56%和44.44%),差异有统计学意义(分别为P<0.01、P<0.01、P<0.01和P<0.05),但p-JNK的表达与临床分期无统计学关系(P>0.05);p-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9的表达与患者的性别、年龄、原发肿瘤部位、病理分型以及有无神经侵袭、复发和转移亦均无相关性(均为P>0.05);p-ERK1/2、P-P38、p-JNK与MMP-2和MMP-9的表达分别呈显著正相关(分别为r=0.786,P<0.001;r=0.796,P<0.001;r=0.824,P<0.001和r=0.768,P<0.001;r=0.581,P<0.01;r=0.604,P<0.01).结论:P-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9的高表达与腺样囊性癌的临床分期及进展密切相关.MAPK/MMPs通路可能参与腺样囊性癌的发生、发展、侵袭及转移过程.     

粘着斑激酶和血管内皮生长因子在唾液腺腺样囊性癌中的表达及意义

目的探讨粘着斑激酶(FAK)和血管内皮生长因子(VEGF)在唾液腺腺样囊性癌(SACC)中的表达及意义。 方法采用SP免疫组织化学方法检测40例SACC、15例正常唾液腺组织中FAK、VEGF、CD34的表达情况。实验数据采用SPSS 19.0统计软件进行Mann-Whitney U检验、方差分析和Fisher′s精确经验,FAK和VEGF表达进行相关分析。 结果40例SACC组织中FAK阳性表达率为87.5%(35/40),对照组为33.33%(5/15),Z=-4.44,P= 0.001;VEGF阳性表达率为90%(36/40),对照组为26.67%(4/15),Z=-4.84,P=0.001;CD34阳性表达率为85%(34/40),对照组为40%(6/15),Z=-4.18,P=0.002,差异均有统计学意义;FAK和VEGF在SACC中的表达与肿瘤血管生成之间具有关联(F_FAK=8.86、P_FAK=0.01;F_VEGF=8.18、P_VEGF=0.01);FAK和VEGF在SACC中的表达与肿瘤的临床分期以及远处转移有关联(P < 0.05),与患者的性别、年龄、肿瘤发生部位和大小、神经侵犯、病理分级、复发情况和淋巴结转移差异无统计学意义(P > 0.05);FAK和VEGF在SACC中的表达存在正相关性(r=0.479,P=0.002)。 结论FAK和VEGF与SACC的发展及侵袭、转移有关联。     

ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas

Oral Diseases (2010) 16 , 774–780 Summary: Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies. Methods: This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis. Results: Strong correlation among the expression of ErbB family receptors was found (ErbB1–ErbB2 P = 0.008, ErbB1‐ErbB4 P = 0.018, EbB2‐ErbB3 P = 0.001, ErbB2‐ErbB4 P = 0.006, ErbB3‐ErbB4 P = 0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006). Conclusions: The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1‐ErbB2, ErbB1‐ErbB4, ErbB2‐ErbB3, ErbB2‐ErbB4, and ErbB3‐ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.     

BDNF、TrkB和E-cadherin在唾液腺腺样囊性癌中的表达及意义

目的 研究BDNF、TrkB和E-cadherin在唾液腺腺样囊性癌（salivary adenoid cystic carcinoma,SACC）中的表达及其与临床病理特点的关系。方法：采用免疫组织化学染色检测76例唾液腺腺样囊性癌和20例正常唾液腺组织中BDNF、TrkB和E-cadherin的表达情况,并分析其与临床病理特征之间的关系。采用SPSS17.0软件包对实验结果进行χ²检验、Wilcoxon秩和检验、Spearman相关系数检验。结果：与正常唾液腺组织相比,BDNF、TrkB在SACC组织中呈现高表达,阳性表达率分别为89.5%、92.1%;E-cadherin呈现中低表达,阳性表达率为46.1%。BDNF的表达与肿瘤临床分期、肿瘤转移显著相关（P<0.05）。TrkB的表达与肿瘤临床分期、神经侵袭、肿瘤转移显著相关（P<0.05）。 E-cadherin的表达与肿瘤病理分型、临床分期、神经侵袭、转移呈显著负相关（P<0.05）。在SACC中,BDNF表达与 E-cadherin表达无显著相关性（P>0.05）,而TrkB表达与E-cadherin表达呈显著负相关（P<0.05）。结论：BDNF、TrkB和E-cadherin的表达与SACC的临床病理特征密切相关,检测3者的表达对SACC的诊断和临床病理研究具有重要的参考价值。     

CCL2和CCR2在唾液腺腺样囊性癌中的表达及意义

目的 研究CCL2和CCR2在唾液腺腺样囊性癌（salivary adenoid cystic carcinoma, SACC）中的表达及其与临床病理特点之间的关系。方法 采用免疫组织化学染色方法检测CCL2、CCR2在60例SACC及12例正常唾液腺组织中的表达情况,并分析其与临床病理特征之间的关系。采用 SPSS 19.0软件包对实验结果进行统计学分析。结果 与正常唾液腺组织相比,CCL2和CCR2在 SACC组织中均呈现高表达,阳性表达率分别为91.7%和88.3%。CCL2和CCR2的表达与肿瘤临床分期、神经侵袭、肿瘤转移显著相关（P<0.05）;与性别、年龄、病理分型无显著相关性（P>0.05）。结论 CCL2、CCR2的表达与SACC的临床病理特征密切相关,检测两者的表达对SACC的诊断和临床病理研究具有重要的参考价值。     

The role of GPC5 in lung metastasis of salivary adenoid cystic carcinoma

Objective

Proteoglycans play a crucial role in salivary adenoid cystic carcinoma (SACC) tumorigenesis, neurotropic growth and lung metastasis. In this study, we investigated the role of GPC5 in the lung metastasis of SACC.

Design

The expression of heparan sulfate proteoglycans (HSPGs) was detected in SACC-M (high lung-metastatic cell line), SACC-2 (low lung-metastatic cell line) and SACC-83 (low lung-metastatic cell line) cells by relative quantitative Real-Time PCR. The expression of GPC5 was detected by immunofluorescence and Western blot analysis in SACC-M, SACC-2 and SACC-83 cells, and by immunohistochemical analysis in primary tumours from 16 cases of SACC patients with or without lung metastasis. GPC5 expression was silenced in SACC-M cells, cell proliferation and tumour growth was evaluated by MTT assay and nude mice model, respectively.

Results

Expression of most HSPGs was decreased in SACC-M cells, but GPC5 expression increased 3.24-fold and 815.69-fold (more than 3-fold) in SACC-M compared with SACC-2 and SACC-83 cells, respectively. Immunohistochemical analysis showed higher expression of GPC5 in SACC with lung metastasis compared to SACC without lung metastasis. The lung metastasis of SACC-M cells in nude mice was obviously decreased after GPC5 silencing (P < 0.05), although GPC5 silencing had no significant effect on SACC-M cell proliferation.

Conclusion

GPC5 may contribute to lung metastasis of SACC.     

Expression of IgSF in salivary adenoid cystic carcinoma and its relationship with invasion and metastasis

BACKGROUND: The aim of the present work was to study the potential effect of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) of immunoglobulin superfamily on the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). METHOD: The expressions of ICAM-1, VCAM-1 and NCAM of forty cases with SACC were examined by immunohistochemical methods using respective kits. RESULTS: A significant relation showed between the expression level and histological differentiation, expression of ICAM-1 and VCAM-1 in solid SACC was greatly increased compared with NCAM; SACC with metastatic lymph node or local recurrence displayed significant relationship to the up-regulation of ICAM-1 and VCAM-1, and to the down-regulation of NCAM. CONCLUSIONS: It is proposed that ICAM-1 and VCAM-1 may play a role in the invasion and metastasis of SACC. NCAM may be an invasion-resistant adhesion molecule.     

细胞外基质与涎腺腺样囊性癌的远处转移

目的 研究涎腺腺样囊性癌与细胞外基质的关系。方法 通过肿瘤手术标本的免疫组化染色和超微结构观察、细胞系体外粘附实验及人工重组基底膜侵袭实验，并采用整合素受体抑制剂精氨酸-天冬氨酸进行体外及荷瘤动物体内实验，观察其预防及治疗肺转移的效果。结果 肿瘤团索周围的基膜样物质呈多层、溶解或断裂现象。出现腺样囊性癌远处转移患者的肿瘤标本组织蛋白酶D免疫组化阳性反应率(75％)明显高于无转移患者(43．8％)。肺高转移涎腺腺样囊性癌细胞株对人工重组基膜的侵袭细胞数明显高于其相应的非高转移细胞系。精氨酸-天冬氨酸在体外能抑制肺高转移涎腺腺样囊性癌细胞对人工重组基膜的侵袭，在体内能显著延长涎腺腺样囊性癌实验性肺转移动物的生存期。结论 涎腺腺样囊性癌的远处转移与细胞外基质有密切关系。     

Coexpression of hypoxia-inducible factor-2α, TWIST2, and SIP1 may correlate with invasion and metastasis of salivary adenoid cystic carcinoma

J Oral Pathol Med (2012) 41 : 424–431 Background: Adenoid cystic carcinoma (ACC) of salivary gland is characterized by advanced local invasion and distant metastasis. Intratumoral hypoxia was reported to be associated with epithelial–mesenchymal transition (EMT) regulators. The purpose of this study was to evaluate the relationship between hypoxia‐inducible factor (HIF)‐2α, TWIST2, and SIP1 expression and the invasion and metastasis in ACC of salivary gland. Method: In vitro we first detected the expression of HIF‐2α, TWIST2, and SIP1 in two ACC cell lines by Western blot and real‐time RT‐PCR. Then, in vivo, a retrospective investigation of 121 patients with ACC from Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University between 1996 and 2005 was carried out using immunohistochemistry to analyze the association between the expression of these three factors and clinical–pathological factors of patients. Results: The protein and mRNA levels of HIF‐2α, TWIST2, and SIP1 in the high‐metastasis cell line (ACC‐M) were much higher than those of the low‐metastasis cell line (ACC‐2). The positive expression of HIF‐2α, TWIST2, and SIP1 (71.07%, 42.98%, and 38.02%, respectively) was associated with the perineural invasion, the local recurrence, and distant metastasis of patients with ACC (P < 0.05). The patients with the positive coexpression of the three factors had a lower survival rate than those with the negative expression (P < 0.05). Conclusion: It is proposed that the elevated expression of HIF‐2α, TWIST2, and SIP1 can contribute to invasion and metastasis of ACC, and there might be some correlation between the hypoxia microenvironment and EMT in ACC.