The Expression And Significance Of Ki-67 And C-fos In The Growth Of Middle Ear Cholesteatoma Epithelium

Objective:To elucidate the biological behavior of cholesteatoma, we studied the expression of nuclear-associated antigen( ki-67 ) and c-fos in the growth of cholesteatoma, perforation of ear drum, and auditory meatal skin. We investigated wether the cholesteatoma in different positions have different biological characteristics. We deliberated the relationship between proliferation and inflammation in the perimatrix in cholesteatoma, also between the proliferation and the destruction of ossicular chain in cholesteatoma.Methods:1) The expression of Ki-67 and c-fos in the 28 specimens cholesteatoma, were respectively compared with that 15 specimens perforation of ear drum and 15 specimens auditory meatal skin. 2) Line correlation analysis was used between expression of Ki-67 and c-fos. 3) According to the origin of the specimens, divided into epitympanum and tympanic sinus, we investigated the respective expression of Ki-67. 4) The destruction of ossicular chain in cholesteatoma, divided into four grades: O0 4 samples, O1 3 samples, O2 9 samples, O3 6 samples, we discussed the Ki-67 expression in different bone destructions. 5) According to the severity of the inflammation in the perimatrix, we divided all samples into two groups, one was the inflammation group included 15 cases, and the other was the non-inflammation group included 13 cases. All the samples were studied by immunohistochemically SP method.Results: 1) The Ki-67 expression of cholesteatoma in the middle ear was higher than perforation of ear drum and auditory meatal skin. The Ki-67 was expressed in the nucleus, and a dot-like as well as suffusion nuclear staining pattern was detected. The Ki-67 expression was restricted in the basal layer of perforation of ear drum and auditory meatal skin, and the positive ratios in the nucleus were rare. But the expression in cholesteatoma extended to the suprabasal and upper layers of the epithelium with an increasing frequency. 2) The c-fos expression in cholesteatoma was also higher than perforation of ear drum and auditory meatal skin, by One-Way analysis of variance, the difference was significant.3) By linear correlation analysis, the correlation was obvious between Ki-67 and c-fos expression in cholesteatoma. 4) And the expression of Ki-67 was the same between epitympanum and tympanic sinus cholesteatoma. 5) There was no obviously statistical significance in the four grades of ossicular chain destruction in cholesteatoma. 6) But even from the same sample, the cholesteatoma from the positions with severe inflammation in the perimatrix counted much higher in Ki-67 expression, and the difference was statistically significant. Conclusions:Ki-67 is a reliable label to react cholesteatoma proliferation, and can offer clinical parameter to evaluate proliferation and bone destruction of cholesteatoma. C-fos is also a good label to reflect proliferation of cholesteatoma. The exact mechanisms in middle ear cholesteatoma have been an exactly complicated process, many kinds of cytokines and transcription factors play a major role of their biological effects. The results suggested that the proliferation in cholesteatoma may play an important role in the pathogenesis. It also suggested that it was the severity of inflammation in the perimatrix what influenced the differences between proliferation and bone disturbance in the cholesteatoma, but not the origins of the cholesteatoma.