TNF-a、MMP-2与P16在中耳胆脂瘤中的表达及意义
发布时间：2019-01-20 15:14
【摘要】： 目的：研究肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-2(MMP-2)及细胞周期蛋白依赖性激酶抑制因子16(P16)在中耳胆脂瘤上皮中的表达情况,探讨它们三者在中耳胆脂瘤上皮中的表达有无相关性及表达水平对中耳胆脂瘤上皮侵袭能力的影响。 方法：标本来自山西医科大学第一临床医学院耳鼻咽喉-头颈外科,收集胆脂瘤型中耳炎病人手术新鲜标本,迅速固定,制成石蜡切片,同时观察病人的骨质破坏程度。采用免疫组化技术和计算机图像定量分析系统法,检测探讨肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、基质金属蛋白酶-2(Matrix metalloproteinases-2,MMP-2)与P16在30例胆脂瘤中的表达,同时观察三者的表达与骨质破坏程度的相互关系,并以10例外耳道皮肤(external ear canal skin,EACS)作为对照,探讨胆脂瘤骨质破坏的可能发生机制。 结果： 1.TNF-α、MMP-2与P16在30例中耳胆脂瘤上皮中表达的阳性率分别为83%、76%、63%,与正常外耳道皮肤相比表达均有显著性差异(P0.05)。TNF-α、MMP-2表达阳性结果为棕黄色颗粒,主要定位于胞浆,TNF-α表达于胆脂瘤上皮细胞及上皮下结缔层基质细胞,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。P16在胞核、胞浆以棕黄色或褐色颗粒为阳性表达,并以胞核为主,位于上皮全层,以角化层、颗粒层表达密度高。 2.胆脂瘤上皮中TNF-α和MMP-2表达呈正相关(r=0.694,P0.01)；而P16与TNF-α和MMP-2的表达无明显相关性(均P0.05)。 3.胆脂瘤侵袭能力与TNF-α和MMP-2表达有显著相关性(均P0.01)。TNF-α和MMP-2表达灰度值越低,表达密度越高,胆脂瘤侵袭能力越强。P16在胆脂瘤中的表达与侵袭能力之间无相关性(P0.05)。 结论： 1.TNF-α、MMP-2与P16在成人中耳胆脂瘤中呈高表达,TNF-α、MMP-2的表达有相关性,提示二者之间存在相互作用,后者可能是前者的诱导因素。 2.TNF-α和MMP-2的表达水平与胆脂瘤的侵袭能力有显著相关性,提示TNF-α和MMP-2可能与胆脂瘤的骨质破坏程度密切相关。P16在中耳胆脂瘤中侵袭能力与P16的表达灰度之间未发现相关性。 3.胆脂瘤中TNF-α、MMP-2的高表达与骨质破坏程度有关指标的检测可为临床保守治疗、评估预后提供参考。 4.P16在胆脂瘤上皮的高度表达有可能是抑制上皮高度增殖的原因之一。
[Abstract]:Objective: to study the expression of tumor necrosis factor- 伪 (TNF- 伪), matrix metalloproteinase-2 (MMP-2) and cyclin dependent kinase inhibitor 16 (P16) in middle ear cholesteatoma. To investigate the relationship between the expression of these three proteins in middle ear cholesteatoma epithelium and the effect of their expression level on the invasion ability of middle ear cholesteatoma epithelium. Methods: the specimens were collected from the Department of Otorhinolaryngology and head and neck surgery of the first College of Clinical Medicine of Shanxi Medical University. Fresh specimens of cholesteatoma type otitis media were collected, fixed quickly and made into paraffin sections, and the degree of bone destruction was observed at the same time. Tumor necrosis factor- 伪 (tumor necrosis factor-alpha,TNF- 伪 and matrix metalloproteinase-2 (Matrix metalloproteinases-2,) were detected by immunohistochemical technique and computer image quantitative analysis system. The expression of MMP-2 and P16 in 30 cases of cholesteatoma was observed. The relationship between the expression of P16 and the degree of bone destruction was observed, and 10 cases of skin (external ear canal skin,EACS of external auditory canal were used as control. To explore the possible mechanism of bone destruction in cholesteatoma. Results: 1. The positive rates of TNF- 伪, MMP-2 and P16 in the epithelium of 30 cases of middle ear cholesteatoma were 837 ~ 7663, respectively. There were significant differences between TNF- 伪, MMP-2 and P16 in normal skin of external auditory canal (P0.05). The positive expression of MMP-2 was brown granules, mainly located in cytoplasm, TNF- 伪 was expressed in epithelial cells of cholesteatoma and stromal cells in subepithelial connective layer, MMP-2 was expressed in all layers of cholesteatoma epithelium, the expression of MMP-2 in basal layer was the strongest. The expression of P16 was weak in the granular layer and keratinocytes, and the positive expression of P16 in the cytoplasm was brownish yellow or brown granules, and mainly in the nucleus, which was located in the whole layer of the epithelium, with the keratosis layer and the granular layer with high expression density. 2. There was a positive correlation between TNF- 伪 and MMP-2 expression in cholesteatoma epithelium (r 0.694U P0.01), but no significant correlation between P16 expression and TNF- 伪 and MMP-2 expression (P0.05). 3. There was a significant correlation between the invasion ability of cholesteatoma and the expression of TNF- 伪 and MMP-2 (P0.01). The lower the gray value of TNF- 伪 and MMP-2 expression, the higher the density of TNF- 伪 and MMP-2 expression. There was no correlation between the expression of P16 in cholesteatoma and invasion ability (P0.05). Conclusion: 1. TNF- 伪, MMP-2 and P16 are highly expressed in adult middle ear cholesteatoma, and the expression of TNF- 伪 and MMP-2 is correlated, suggesting that there is interaction between them, and the latter may be the inductive factor of the former. 2. 2. The expression levels of TNF- 伪 and MMP-2 were significantly correlated with the invasiveness of cholesteatoma. It is suggested that TNF- 伪 and MMP-2 may be closely related to the degree of bone destruction in cholesteatoma, but there is no correlation between the invasion ability of P16 in middle ear cholesteatoma and the gray level of P16 expression. 3. The high expression of TNF- 伪 and MMP-2 in cholesteatoma may provide reference for clinical conservative treatment and prognosis evaluation. The high expression of 4.P16 in the epithelium of cholesteatoma may be one of the reasons to inhibit the high proliferation of the epithelium.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764
本文编号：2412144
[Abstract]:Objective: to study the expression of tumor necrosis factor- 伪 (TNF- 伪), matrix metalloproteinase-2 (MMP-2) and cyclin dependent kinase inhibitor 16 (P16) in middle ear cholesteatoma. To investigate the relationship between the expression of these three proteins in middle ear cholesteatoma epithelium and the effect of their expression level on the invasion ability of middle ear cholesteatoma epithelium. Methods: the specimens were collected from the Department of Otorhinolaryngology and head and neck surgery of the first College of Clinical Medicine of Shanxi Medical University. Fresh specimens of cholesteatoma type otitis media were collected, fixed quickly and made into paraffin sections, and the degree of bone destruction was observed at the same time. Tumor necrosis factor- 伪 (tumor necrosis factor-alpha,TNF- 伪 and matrix metalloproteinase-2 (Matrix metalloproteinases-2,) were detected by immunohistochemical technique and computer image quantitative analysis system. The expression of MMP-2 and P16 in 30 cases of cholesteatoma was observed. The relationship between the expression of P16 and the degree of bone destruction was observed, and 10 cases of skin (external ear canal skin,EACS of external auditory canal were used as control. To explore the possible mechanism of bone destruction in cholesteatoma. Results: 1. The positive rates of TNF- 伪, MMP-2 and P16 in the epithelium of 30 cases of middle ear cholesteatoma were 837 ~ 7663, respectively. There were significant differences between TNF- 伪, MMP-2 and P16 in normal skin of external auditory canal (P0.05). The positive expression of MMP-2 was brown granules, mainly located in cytoplasm, TNF- 伪 was expressed in epithelial cells of cholesteatoma and stromal cells in subepithelial connective layer, MMP-2 was expressed in all layers of cholesteatoma epithelium, the expression of MMP-2 in basal layer was the strongest. The expression of P16 was weak in the granular layer and keratinocytes, and the positive expression of P16 in the cytoplasm was brownish yellow or brown granules, and mainly in the nucleus, which was located in the whole layer of the epithelium, with the keratosis layer and the granular layer with high expression density. 2. There was a positive correlation between TNF- 伪 and MMP-2 expression in cholesteatoma epithelium (r 0.694U P0.01), but no significant correlation between P16 expression and TNF- 伪 and MMP-2 expression (P0.05). 3. There was a significant correlation between the invasion ability of cholesteatoma and the expression of TNF- 伪 and MMP-2 (P0.01). The lower the gray value of TNF- 伪 and MMP-2 expression, the higher the density of TNF- 伪 and MMP-2 expression. There was no correlation between the expression of P16 in cholesteatoma and invasion ability (P0.05). Conclusion: 1. TNF- 伪, MMP-2 and P16 are highly expressed in adult middle ear cholesteatoma, and the expression of TNF- 伪 and MMP-2 is correlated, suggesting that there is interaction between them, and the latter may be the inductive factor of the former. 2. 2. The expression levels of TNF- 伪 and MMP-2 were significantly correlated with the invasiveness of cholesteatoma. It is suggested that TNF- 伪 and MMP-2 may be closely related to the degree of bone destruction in cholesteatoma, but there is no correlation between the invasion ability of P16 in middle ear cholesteatoma and the gray level of P16 expression. 3. The high expression of TNF- 伪 and MMP-2 in cholesteatoma may provide reference for clinical conservative treatment and prognosis evaluation. The high expression of 4.P16 in the epithelium of cholesteatoma may be one of the reasons to inhibit the high proliferation of the epithelium.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764
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