Expression Of Gelatinases And Their Inhibitors In Human Middle Ear Cholesteatoma And Its Significance

Objective:This study aimed to analyse the expression of gelatinises (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-2 and TIMP-1)in middle ear cholesteatoma and to investigate the correlations between their expression. Meanwhile , we studied the etiopathogenesis of bone absorption of middle ear cholesteatoma further.Methods:The expression of MMP-2 , MMP-9 , TIMP-2 and TIMP-1 proteins were detected in the specimens of 52 cases of middle ear cholesteatomas and 10 cases of the normal skin of external auditory meatus with immunohistochemiscal staining( SP method ). Meanwhile, the positive results were contrasted.Results: (1)There were significantly stronger expression of MMP-2 , MMP-9 proteins in most of 52 cases of middle ear cholesteatoma than those in 10 cases of the normal skin of external auditory meatus. The positive expression rates of MMP-2 and MMP-9 proteins were78.8%and 82. 7% , the positive cell counts were 38.1516±14. 6233 and 41. 7237 ± 13.1666 in middle ear cholesteatoma, respectively.This expression tended to be increased greatly compared with the positive expression rates of MMP-2 and MMP-9 proteins were 20%and 30% the positive cell counts were 8.0525 ± 5. 7165 and 10.8639 ± 4.2654 in the normal skin of external auditory meatus, respectively. (P<0 .05). There was significant difference of the expression of MMP-2 and MMP-9 proteins between middle ear cholesteatoma and normal skin of external auditory meatus. There were weak expression of TIMP-2 and TIMP-1 proteins in middle ear cholesteatoma and normal skin of external auditory meatus. The positive expression rates of TIMP-2 and TIMP-1 proteins were 38. 5%and 40.4% , the positive cell counts were 17.5423 ± 7.8215 and 18.9168 ± 8.2956 in middle ear cholesteatoma, respectively. This expression tended not to be increased greatly compared with the positive expression rates of TIMP-2 and TIMP-1 proteins were 30%and 30%> the positive cell counts were 15. 2871 + 3. 6509 and 16.4146 ±5.5913 in normal skin of external auditory meatus, respectively (P >0 .05). There was no statistic significance of the difference of the positive expression of TIMP-2 and TIMP-1 proteins between middle ear cholesteatoma and normal skin of external auditory meatus. ?There were cytoplasmic staining patterns of MMP-2 , MMP-9 , TIMP-2 and TIMP-1 positive cell, while no nuclear staining patterns. The positive expression of MMP-2, 9 was seen in all layers of the cholesteatoma epithelium and the stain was strongest in basement membrane . In addition to, the strong positive expression of MMP-2 and MMP-9 proteins was seen in granulation tissue. But in the skin of external auditory meatus., the positive expression of MMP2, 9 could be mostiy seen in the layers of stratum basale and stratum spinosum. The positive expression of TIMP-2 and TIMP-1 proteins in cholesteatoma epithelium and normal skin of external auditory meatus were mostly seen in the layers of stratum basale and stratum spinosum. ? In cholesteatoma epithelium, the positive expression rates of MMP-2 and MMP-9 proteins in children group, which were 91. 7%and 100 %, there was no statistic significance of the difference in comparison with those in adults group , which were 75%and 75.8%, respectively. The positive expression rates of MMP-2 and MMP-9 proteins in extensive cholesteatoma, which were 96. 9%and 100%respectively, were significantly increased in comparison with in localized cholesteatoma , which were 48.4 %and 52.6% respectively (P<0.001) . No significant difference was observed between the male and the female groups (P>0 .05). The positive expression rates of TIMP-2 and TIMP-1 proteins in children group, which were 50% and 41.6%, there was no significant difference in comparison with in adults group which were 35%and 40%, respectively. The positive expression rates of TIMP-2 and TIMP-1 proteins in extensive cholesteatoma, which were 42.4%and 45. 5%respectively, there was nosignificant difference in comparison with in localized cholesteatoma which were 31.6% and 31.6%, respectively(P > 0 .05). No significant difference was observed between the male and the female groups (P>0 . 05). @ In cholesteatoma epithelium,. there was significantly positive correlation between the expression of MMP-2 and MMP-9 proteins. There were positive correlations between MMP-2 and TIMP-2 proteins , MMP-9 and TIMP-1 proteins. But the increased extent of the expressions of TIMP-2 and TIMP-1 proteins was significantly lower than that of MMP-2 and MMP-9 proteins . So the ratio of MMP-2 and TIMP-2 proteins , MMP-9 and TIMP-1 proteins were increased and the imbalance between their expressions was caused. In addition to, there was no correlation between TIMP-2 and TIMP-1 proteins . Conclusion: The imbalance between the expression of MMP-2 and TIMP-2 proteins , MMP-9 and TIMP-1 proteins in cholesteatoma may cause the increase of proteolytic activity and may contribute to the occurrence and development of cholesteatoma. So it may be one of vital factors in the bone destruction associated with cholesteatoma. Artificially induced expression of TIMP-2 and TIMP-1 proteins or interrupting the expression of MMP-2 and MMP-9 proteins probably inhibits the pathogenesis of bone destruction and postoperative recurrence of middle ear cholesteatoma. This study may provide a new auxiliary way for therapy of middle ear cholesteatoma.