MMP-13和MMP-9与中耳胆脂瘤组织侵袭性的研究

目的究MMP-13和MMP-9在中耳胆脂瘤组织的表达及其临床意义,探讨其相互作用机制及骨质破坏的相关性。方法用免疫组化SP法检测176例中耳胆脂瘤及外耳道正常皮肤中MMP-13和MMP-9的表达,并进行平均光密度值的定量分析与周围骨质破坏范围情况。结果 MMP-13和MMP-9均表达于胞质中,MMP-13和MMP-9在胆脂瘤组织中均呈高表达,平均光密度值显著高于外耳道正常上皮组织,且两者表达呈正相关(P0.01)。随着周围骨质破坏范围增大,MMP-13和MMP-9表达越高。结论 MMP-13和MMP-9共同参与胆脂瘤组织对骨质的破坏,可能主要通过MMP-13激活MMP-9途径来参与胆脂瘤组织的侵袭。     

RANKL和IL-17A在中耳胆脂瘤中的表达及相关性研究

目的观察破骨细胞分化因子（RANKL）和白介素-17A（IL-17A）在中耳胆脂瘤组织中的表达,探讨二者在中耳胆脂瘤骨质破坏机制中的作用。方法采用免疫组织化学两步法和计算机图像定量分析法,检测RAN-KL、IL-17A在25例中耳胆脂瘤上皮、16例胆脂瘤周围肉芽组织及15例正常外耳道皮肤中的表达,同时观察二者的表达与临床听小骨骨质破坏程度的相互关系。结果（1）RANKL、IL-17A在胆脂瘤上皮及胆脂瘤周围肉芽组织中表达增高,分别与正常对照组比较,差异均有统计学意义（tRANKL=9.864、5.630,均P〈0.05;tIL-17A=13.905、9.011,均P〈0.05）,且二者的表达与骨质破坏程度相关。（2）在胆脂瘤上皮及胆脂瘤周围肉芽组织中,RANKL与IL-17A的表达呈正相关（r上皮=0.692,r肉芽=0.538,P〈0.05）。结论RANKL及IL-17A在中耳胆脂瘤组织中呈高表达,与骨质破坏程度成正比,表明其与胆脂瘤骨质破坏机制密切相关;RANKL与IL-17A表达有相关性,提示二者之间可能存在相互作用。     

两种基质金属蛋白酶在胆脂瘤和中耳癌中的表达

目的探讨基质金属蛋白酶（matrix metalloproteinases, MMP）的MMP-2和MMP-9在胆脂瘤和中耳癌中的表达差异及其在骨浸润作用。方法采用免疫组织化学方法检测36例胆脂瘤上皮,10例胆脂瘤外耳道皮肤、16例中耳癌组织及正常组织中MMP-2和MMP-9的表达。结果①MMP-2和MMP-9在胆脂瘤上皮染色最强。而且在上皮组织的各层细胞均有表达,基底膜染色最强。②胆脂瘤上皮中的MMP-2和MMP-9的表达明显高于其对应的外耳道皮肤和正常外耳道上皮。MMP-2阳性表达在胆脂瘤上皮中为83%,胆脂瘤外耳道上皮为50%,正常外耳道皮肤2例有微弱表达。③16例中耳鳞癌组织中,MMP-9的阳性表达率为50%（8/16）,MMP-2的阳性表达率为56.25%（9/16）,表达水平与肿瘤的病理分级和临床分期有关。④中耳癌组织中MMP-2的表达与MMP-9表达不一致,而胆脂瘤组织中MMP-2和MMP-9的表达密切相关。结论胆脂瘤向周围骨质侵袭的特性与中耳癌相似,MMPs家族及其抑制剂之间的平衡紊乱所致的蛋白水解酶活性增高是引起中耳胆脂瘤骨吸收的原因之一。     

基质金属蛋白酶2和9在不同部位的中耳胆脂瘤的表达

目的 探讨基质金属蛋白酶(matrix metalloproteinase,MMP)2和9在不同部位的中耳胆脂瘤的表达差异及其骨破坏作用.方法 采用免疫组化方法 检测上鼓室胆脂瘤18例、鼓室窦胆脂瘤16例、胆脂瘤患者外耳道皮肤10例、正常外耳道皮肤10例中MMP-2和MMP-9的表达.结果 MMP-2、MMP-9在上鼓室胆脂瘤和鼓室窦胆脂瘤上皮各层细胞中均有表达,基底层表达最强;鼓室窦胆脂瘤较上鼓室胆脂瘤染色深.正常外耳道皮肤和胆脂瘤患者外耳道皮肤有非常浅的表达,主要分布在基底层细胞的胞质中.MMP-2、MMP-9在正常外耳道皮肤和胆脂瘤患者外耳道皮肤的表达差异无统计学意义(P值均<0.05);上鼓室胆脂瘤和鼓室窦胆脂瘤中MMP-2、MMP-9的表达均高于正常外耳道皮肤和胆脂瘤患者外耳道皮肤,差异有统计学意义(P值均<0.05);鼓室窦胆脂瘤中MMP-2、MMP-9的表达高于上鼓室胆脂瘤,差异具有统计学意义(P值均>0.05).胆脂瘤上皮中MMP-2和MMP-9的表达呈显著正相关(r=0.974,P<0.01),MMP-2的表达高于MMP-9.MMP-2和MMP-9的表达与听小骨的破坏程度呈正相关(r=0.789及0.803,P值均<0.01).结论 胆脂瘤型中耳炎骨质破坏过程中MMP起重要作用.鼓室窦胆脂瘤的骨质破坏程度较上鼓室胆脂瘤重,更具侵袭性,更容易产生颅内外并发症.     

MMP-9在中耳胆脂瘤中的表达和意义

目的 研究基质金属蛋白酶-9(matrix metalloproteinase,MMP-9)在中耳胆脂瘤上皮中的表达,并探讨其与中耳胆脂瘤的血管形成以及胆脂瘤侵蚀行为的关系.方法采用免疫组织化学SP法检测MMP-9、Ⅳ型胶原蛋白在44例患者中耳胆脂瘤组织标本与10例正常外耳道组织中的表达.结果 MMP-9在胆脂瘤上皮各层均有表达,在外耳道皮肤中为弱阳性表达;胆脂瘤基质周围微血管计数均数高于正常外耳道皮肤,二者差异具有统计学意义(P＜0.05);MMP-9在胆脂瘤中的表达与周围微血管计数间呈正相关关系.结论 MMP-9可能在中耳胆脂瘤血管生成中起重要作用.     

Caspase-9和Livin在中耳胆脂瘤中的表达及意义

目的研究凋亡相关蛋白Caspase-9和Livin在中耳胆脂瘤上皮组织中的表达,揭示二者在中耳胆脂瘤发生发展中的作用。方法采用免疫组化法检测凋亡促进蛋白Caspase-9和凋亡抵制蛋白Livin在23例中耳胆脂瘤及10例正常外耳道皮肤组织中的表达,对染色结果进行量化处理和统计学分析。结果 Caspase-9和Livin蛋白在中耳胆脂瘤上皮的表达均高于在正常外耳道皮肤中的表达(P<0.01);二者在胆脂瘤中的表达呈正相关,相关系数r=0.848(P<0.05)。结论凋亡促进蛋白Caspase-9和凋亡抑制蛋白Livin在中耳胆脂瘤中的表达同步升高,提示就凋亡过程而言,二者达到了新的平衡。     

Toll样受体在慢性化脓性中耳炎和中耳胆脂瘤中的差异表达及其意义

目的 检测Toll样受体2( toll-like receptor 2,TLR2)和Toll样受体4(toll-like receptor 4,TLR4)在慢性化脓性中耳炎、中耳胆脂瘤中的表达,探讨其在慢性化脓性中耳炎和中耳胆脂瘤发病中的作用.方法 选取耳硬化症患者(对照组)、慢性化脓性中耳炎患者(化脓性中耳炎组)、中耳胆脂瘤患者(中耳胆脂瘤组)各30例,应用实时定量聚合酶链反应( real-time PCR)、蛋白质印迹法( Western blot)、免疫组化检测TL R2/TLR4在正常外耳道皮肤,慢性化脓性中耳炎黏膜、肉芽组织,中耳胆脂瘤患者黏膜、肉芽组织及胆脂瘤囊壁中的表达,并比较表达程度的差异.结果 ①TLR2/TLR4mRNA及蛋白质在正常外耳道皮肤,慢性化脓性中耳炎中耳黏膜、肉芽组织,胆脂瘤的中耳黏膜、肉芽组织及胆脂瘤囊壁均有表达.②TLR2/TLR4 mRNA及其蛋白质在慢性化脓性中耳炎及胆脂瘤黏膜中的表达均高于正常外耳道皮肤(P值均＜0.05),在胆脂瘤囊壁中的表达低于正常外耳道皮肤(P值均＜0.05),两组黏膜中TLR2/TLR4的表达差异无统计学意义(P值均＞0.05).③TLR2/TLR4mRNA及蛋白质在两组中耳炎肉芽组织中的表达均高于正常外耳道皮肤(P值均＜0.01),且TLR2mRNA在中耳胆脂瘤肉芽组织中的表达高于慢性化脓性中耳炎(P＜0.05).④TLR2/TLR4阳性细胞主要分布在肉芽组织中,且明显多于正常外耳道皮肤,但胆脂瘤囊壁中的阳性细胞少于正常外耳道皮肤.结论 TLR2和TLR4在正常外耳道皮肤、慢性化脓中耳炎及中耳胆脂瘤中均有表达,提示中耳具有TLR2、TLR4参与调节的固有免疫系统,但二者的差异性表达也提示其在慢性化脓性中耳炎和中耳胆脂瘤的发病中所起的作用不同.     

基质金属蛋白酶-9和肿瘤坏死因子-α在中耳胆脂瘤中的表达

目的 :观察基质金属蛋白酶 (MMP) 9、肿瘤坏死因子 (TNF) α在胆脂瘤组织中的表达 ,探讨二者在胆脂瘤骨质破坏中的作用。方法 :采用免疫组织化学技术 (SP法 )和计算机图像定量分析法 ,检测TNF α、MMP 9在 2 2例胆脂瘤及 2 0例外耳道皮肤中的表达 ,同时观察二者的表达与临床上听小骨骨质破坏程度的相互关系。结果 :MMP 9表达于胆脂瘤上皮下结缔组织基质细胞 ,TNF α在上皮层及上皮下结缔组织基质细胞中有高度表达 ,定量分析显示胆脂瘤组织中二者的含量显著高于外耳道皮肤 (P <0 .0 5 ) ,并且二者的表达与骨质破坏的程度有关。结论 :MMP 9和TNF α在胆脂瘤组织中呈高表达 ,且与骨质破坏程度呈正比 ,表明其与胆脂瘤的骨质破坏密切相关 ;并且MMP 9和TNF α的表达有相关性 ,提示二者之间可能存在相互作用 ;MMP 9仅在胆脂瘤基质细胞中表达 ,TNF α也在基质细胞中表达 ,提示基质细胞在胆脂瘤的骨质破坏中起着重要的作用     

破骨细胞分化因子及其相关因子在中耳胆脂瘤组织的表达

目的探讨破骨细胞分化因子（nuclear factor-kappa B ligand,RANKL）和其配体核因子-κB受体活化因子（receptor activator of nuclear factor-kappa B,RANK）及假性受体骨保护素（osteoprotegerin,OPG）即RANK-RANKL-OPG系统在中耳胆脂瘤的作用,儿童中耳胆脂瘤较成人骨质破坏严重的原因。方法应用免疫组织化学SP法观察RANKL和OPG在21例成人中耳胆脂瘤组织、17例儿童中耳胆脂瘤组织和18例正常外耳道深部皮肤中的表达,对染色结果进行量化处理和统计学分析。结果RANKL和RANKL/OPG比值在胆脂瘤的表达量明显高于外耳道皮肤,儿童胆脂瘤高于成人,差异有统计学意义（P〈0.05）。结论①RANKL和RANKL/OPG比值的增高与胆脂瘤的骨质破坏有关,在中耳胆脂瘤骨质破坏的机制中起重要作用;②儿童中耳胆脂瘤RANKL/OPG比值较高,这可能是导致儿童中耳胆脂瘤比成人发展快,骨质破坏严重的一个重要原因。     

两种基质金属蛋白酶在胆脂瘤和中耳癌中的表达

目的 探讨基质金属蛋白酶（matrix metalloproteinases,MMP)的MMP－2和MMP－9的胆脂瘤和中耳癌中的表达差异及其在骨浸润作用。方法 采用免疫组织化学方法检测36例胆脂瘤上皮，10例胆脂瘤外耳道皮肤、16例中耳癌组织及正常组织中MMP－2和MMP－9的表达。结果 ①MMP－2和MMP－9在胆脂瘤上皮染色最强。而且在上皮组织的各层细胞均有表达，基底膜染色最强。②胆脂瘤上皮中的MMP－2和MMP－9的表达明显高于其对应的外耳道皮肤和正常外耳道上皮。MMP－2阳性表达在胆脂瘤上皮中为83％，胆脂瘤外耳道上皮为50％，正常外耳道皮肤2例有微弱表达。③16例中耳鳞癌组织中，MMP－9的阳性达率为50％（8／16），MMP－2的阳性表达率为56.25%(9/16)，表达水平与肿瘤的病理分级和临床分期有关。④中耳癌组织中MMP－2的表达与MMP－9表达不致，而胆脂瘤组织中MMP－2和MMP－9的表达密切相关。结论 胆脂瘤向周围骨质侵袭的特性与中耳癌相似，MMPs家族及其抑制剂之间的平衡紊乱所致的蛋白水解酶活性增高是引起中耳胆脂瘤骨吸收的原因之一。     

表皮生长因子受体和Ki67及p16在成人中耳胆脂瘤中的表达

目的:研究表皮生长因子受体(EGFR)、Ki67、p16在成人中耳继发性胆脂瘤上皮中的表达情况,分析它们之间的相互关系,探讨其表达对胆脂瘤上皮侵袭能力的影响。方法:应用免疫组织化学SP染色方法检测EGFR、Ki67和p16在30例成人中耳胆脂瘤上皮、21例成人胆脂瘤患者外耳道正常皮肤、17例正常人外耳道中的表达情况,应用计算机图像分析系统对其阳性表达进行定量分析。结果:EGFR、Ki67、p16在成人中耳继发性胆脂瘤上皮中阳性表达率分别为70.0%,60.0%,46.7%,与外耳道正常皮肤相比表达均差异有统计学意义。成人中耳胆脂瘤中EGFR、Ki67与p16之间表达均无相关性(均P>0.05)。胆脂瘤侵袭能力与EGFR、Ki67表达有显著相关性(均P<0.01)。EGFR、Ki67表达灰度值越低,表达密度越高,胆脂瘤侵袭能力越强。p16在成人中耳胆脂瘤中的表达与侵袭能力之间无相关性(P>0.05)。EGFR、Ki67、p16在成人中耳胆脂瘤中阳性细胞主要分布于上皮全层,以基底层和棘层为著,呈高度表达;而在对照组中阳性细胞仅在基底层表达,呈弱表达。结论:EGFR、Ki67、p16在成人中耳胆脂瘤中呈高表达,EGFR、Ki67的表达与成人中耳胆脂瘤的侵袭能力有高度相关性,提示成人中耳胆脂瘤具有高度增殖能力,其中细胞因子EGFR、Ki67、p16起到重要的作用。     

Up-regulation of matrix metalloprotease-9 in middle ear cholesteatoma – correlations with growth factor expression in vivo?

The role of matrix metalloproteases and their regulation in the pathology of middle ear cholesteatoma is still unclear. Recently we have demonstrated that incubation of keratinocytes with cholesteatoma debris and granulation tissue extracts causes induction of gelatinase B (matrix metalloproteinase-9, MMP-9) secretion in vitro. Antibodies against a variety of growth factors revealed some inhibitory effect on MMP-9 induction, caused by debris or granulation tissue extracts. In order to investigate the coherence of growth factor expression and matrix metalloproteinase activity in vivo in middle ear cholesteatoma, we performed quantitative gelatin zymographic analysis with tissue homogenates of 37 cholesteatoma and nine external ear canal skin (EACS) samples. Furthermore we quantified levels of the cytokines IL-1α, IL-1β, TNF-α, TGF-β and EGF present in tissue extracts, using enzyme-linked immunosorbent assays (ELISA), and correlated cytokine concentrations with gelatinolytic activities. Zymographic analysis revealed a highly heterogeneous expression of gelatinase A and B in cholesteatoma specimens. As shown previously, MMP-9, but not MMP-2, was increased in cholesteatoma when compared to EACS samples. ELISA studies revealed a significantly elevated ¶IL-1α level in cholesteatoma. Regression analysis involving gelatinolytic activity and cytokine concentrations in tissue homogenates showed no statistically significant correlation between expression of gelatinases and the cytokines IL1-α, IL1-β, TNF-α, TGF-β or EGF. The discrepancy between in vitro observations and the situation in vivo is discussed critically.     

基质金属蛋白酶-2及其抑制剂和白细胞介素-6在中耳胆脂瘤的表达及意义

目的研究基质金属蛋白酶-2（matrix metalloproteinase-2,MMP-2）及其抑制剂（tissue inhibitor of metalloproteinase, TIMP-2）和白细胞介素-6（interleukin-6,IL-6）在中耳胆脂瘤中的表达,探讨其表达在胆脂瘤溶骨机制中的作用.方法应用免疫组化技术检测32例患者中耳胆脂瘤组织和10例正常人外耳道皮肤组织中MMP-2、 TIMP-2和IL-6的表达.结果 MMP-2在胆脂瘤上皮各层细胞中均有表达,基底层表达最强,棘层次之,颗粒层及角质层细胞表达较弱;TIMP-2在基底细胞层和棘细胞层有少量表达;IL-6的表达分布于胆脂瘤上皮全层,但在基底层细胞表达最弱,棘细胞层、颗粒层和角质层依次递增,染色最强的部位是颗粒层和角质层,而正常外耳道皮肤未见MMP-2、 TIMP-2、IL-6的表达.结论在胆脂瘤组织中存在MMP-2与TIMP-2的表达失衡,导致胆脂瘤的骨质破坏.同时胆脂瘤上皮高表达IL-6可能是MMPs过表达的原因.     

Expression of matrix metalloproteinasa-2,9 in cholesteatoma and middle ear cancer]

OBJECTIVE: To study various expressions and roles of MMP-2, 9 in cholesteatoma and middle ear cancer. METHODS: MMP-2 and MMP-9 were detected with immunohistochemical methods using monoclonal antibody in 36 cholesteatomas, 10 CAMS and 16 middle ear cancer. RESULTS: The stain in cholesteatoma was stronger than that in CAMS and NAMS. Expressions of MMP-2, 9 were seen in all layers of the epithelium in CA and the stain was strongest in basement membrane. The positive rates of stain was 83% and 50% in CA and CAMS respectively. There was weak stain in 2 NAMS. In middle ear cancer, the expression rates of MMP-9 and MMP-2 were 50% (8/16) and 56.25% (9/16) respectively. The expression level was correlated with tumor differentiation and its clinical stage. Expressions of MMP-2 and MMP-9 were closely related in cholesteatoma. There was no relationship between expressions of MMP-2 and MMP-9 in middle ear cancer. CONCLUSION: Cholesteatoma has a similar feature with middle ear cancer in invading surrounding of surround bone matrix. The disorder between MMPs and its inhibitor was one of reasons for bone absorption of cholesteatoma and middle ear cancer.     

Expression of EGFR and Microvessel Density in Middle Ear Cholesteatoma

Objectives

Cholesteatoma destructs bony tissue by the interactions between hyperproliferative epithelial cells and subepithelial inflammatory cells. The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and microvessel density (MVD) in middle ear cholesteatoma tissue in an effort to determine the relationship between expression of EGFR and neovascularization.

Methods

We evaluated the expression of EGFR and MVD by immunohistochemical staining for CD31 and Factor VIII in 32 cholesteatoma tissue samples and 7 normal postauricular skin samples. We also analyzed the correlation between EGFR expression and MVD.

Results

The expression of EGFR was higher in cholesteatoma than in postauricular skin, but the difference was not statistically significant. EGFR was more highly expressed in the suprabasal layer than in the basal layer. Using CD31 and Factor VIII, we analyzed the MVD and found that it was significantly higher in cholesteatoma than in postauricular skin, and significantly correlated with the expression of EGFR.

Conclusion

Our results suggest that overexpression of EGFR and neovascularization are correlated with the growth of cholesteatoma.     

Induction of matrix metalloproteinases in keratinocytes by cholesteatoma debris and granulation tissue extracts

Although it is generally accepted that destruction and remodeling of temporal bone associated with middle ear cholesteatoma is mainly caused by the action of osteoclasts, it has been shown that neutral collagenases also play a role in predigesting the osteoid layer and exposing the mineralized bone to osteoclastic activity. Here we show that gelatinase B (matrix metalloproteinase-9) is over-expressed in cholesteatoma compared to external ear canal skin (EACS). Expression of MMP-9 in cholesteatoma mainly occurs in suprabasal layers, and more rarely in basal layers of cholesteatoma epithelium, as well as in inflammatory cells of the perimatrix. We further analyzed the influence of cholesteatoma debris, cholesteatoma granulation tissue, and cholesteatoma components such as keratin, cholesterol and bacterial endotoxin on the expression of MMPs in EACS keratinocytes. We show that cholesteatoma debris and granulation tissue extract both induced the secretion of MMP-9 by EACS keratinocytes, while keratin, bacterial lipopolysaccharide (LPS) or cholesterol did not show any effect. We further performed co-incubation and immunoprecipitation experiments using neutralizing interleukin-1α, EGF, TGF-β, TGF-α, interleukin-6 and TNF-α antibodies. Inhibition of MMP-9 up-regulation by debris or granulation tissue extract could be revealed with diverse cytokine antibodies. The results are discussed with regard to previously published studies. Received: 8 October 1999 / Accepted: 8 March 2000     

基质金属蛋白酶及其抑制剂和转化生长因子—β1在中耳胆脂瘤的表达

目的 探讨基质金属蛋白酶－1（matrix metalloproteinase-1，MMP－1）及其抑制剂金属蛋白酶组织抑制剂－1（tissue inhibitor of metalloproteinase-1，TIMP－1）和影响二者作用的转化生长因子β(transforming growth factor-1，TGF－β1）在中耳胆脂瘤中的表达。方法 采用免疫组化技术检测MMP－1、TIMP－1及TGF－β1在中耳胆脂瘤（41例）和外耳道骨部正常皮肤（15例）中的表达。结果 TGF－β1、MMP-1及TGF－β在中耳胆脂瘤（41例）和外耳道骨部正常皮肤（15例）中的表达。结果 TGF－β、MMP－1及TIMP－1在中耳胆脂瘤中的阳性表达率分别为95．12％、85．37％、9．76％，与外耳道正常皮肤相比，TGF－β和MMP－1的表达均差异有显著性。而TIMP－1的表达差异无显著性。TGF－β与MMP－1表达间存在正相关，与TIMP－1表达间无相关性。结论 MMP－1与TIMP－1表达间的失衡，可能在胆脂瘤的骨吸收中起到了重要作用。     

继发性胆脂瘤中CCL27的定位及检测

目的 明确趋化因子CCL27在继发性中耳胆脂瘤中的病理学表达,探讨可能的临床意义。 方法 应用免疫组织化学SP法检测CCL27在继发性中耳胆脂瘤(n=30)及正常耳后皮肤组织(n=30)的表达情况,并分析该趋化因子与胆脂瘤病理学之间的联系。 结果 继发性胆脂瘤、耳后皮肤组织中CCL27的阳性率分别为6.7%和33.3%,差异有统计学意义(P=0.021)。 结论 继发性胆脂瘤组织中CCL27的低表达可能与胆脂瘤的增殖过于活跃有关,CCL27可能在继发性中耳胆脂瘤发病过程中扮演重要角色。     

The expression of matrix metalloproteinase-9 and tumor necrosis factor-alpha in cholesteatoma]

OBJECTIVE: To observe the expression of MMP-9, TNF-alpha in cholesteatoma and to determine their roles in the destruction of bone. METHOD: Immunohistochemical method (SP) and the computer image quantitative analysis were used to examine the expression of TNF-alpha, MMP-9 in 22 samples from cholesteatoma and 20 normal cases. At the same time, the correlation between the expressions of the two indexes and the erosion of ossicles were observed. RESULT: MMP-9 protein was only expressed in cholesteatoma stromal cells. TNF-alpha was expressed in both epithlium and stromal cells. The results of the computer image quantitative analysis showed that the mean optical density of MMP-9 and TNF-alpha in cholesteatoma were higher than that in normal skin epithelial tissue (P < 0.05), in addition, the two indexes were relative to the extent of ossicle destruction. CONCLUSION: MMP-9 and TNF-alpha are overexpressed in cholesteatoma and they are associated with ossicle destruction, which shows that MMP-9 and TNF-alpha are responsible for bone destruction in cholesteatoma; MMP-9 and TNF-alpha have a correlation in their expression, which suggest that the two factors act on each other possibly; Overexpression of MMP-9 is only observed in stromal cells and the immunostain of TNF-alpha also is observed in stromal cells which indicates that stromal cells play an important role in bone destruction.     

端粒酶催化亚单位和c-Myc蛋白在中耳胆脂瘤上皮中的表达及意义

目的:观察端粒酶催化亚单位(TERT)和癌基因cMyc的表达产物(cMyc蛋白)在中耳胆脂瘤上皮中的表达情况,分析其在胆脂瘤上皮增殖演变过程中的作用。方法:应用SP法和计算机图像分析系统,检测TERT、cMyc蛋白在32例胆脂瘤组织和14例胆脂瘤患者外耳道皮肤中的表达情况,并进行比较。结果:TERT和cMyc蛋白在所有胆脂瘤上皮各层细胞均存在较强表达,外耳道皮肤表达较弱。各组间胆脂瘤上皮各指标平均阳性细胞率和平均吸收度(平均灰度的倒数),均高于外耳道皮肤,差异有统计学意义(P<0.05);皮下结缔组织伴有大量的炎症细胞,如:淋巴细胞、浆细胞、中性粒细胞和巨噬细胞;胆脂瘤上皮中TERT和cMyc蛋白之间存在正相关关系(P<0.01)。结论:TERT和cMyc蛋白在胆脂瘤上皮的表达从不同方面反映了胆脂瘤上皮的过度增生和角化,二者在胆脂瘤的发病过程中有协同作用;上皮下炎症反应可能是角化细胞过度增殖的一个原因。