Taichi Kan1,2, Hiromi Ueda3, Taishi Takahara4, Yoshimasa Tsuchiya1, Mayuko Kishimoto1, Yasue Uchida1, Tetsuya Ogawa1, Wataru Ohashi5, Toyonori Tsuzuki4, Yasushi Fujimoto1. 1. Department of Otorhinolaryngology, Aichi Medical University School of Medicine, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan. 2. Department of Otorhinolaryngology, Nagoya Ekisaikai Hospital, 4-66, Shonencho, 11 Nakagawa-ku, Nagoya, Aichi 454-0854, Japan. 3. Ear Surgical Center, Meitetsu Hospital, 2-26-11, Sako, Nishi-ku, Nagoya, Aichi 451-8511, Japan. 4. Department of Surgical Pathology, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan. 5. Division of Biostatistics, Clinical Research Center, Aichi Medical University School of Medicine, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
Abstract
OBJECTIVE: Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase-2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed MMP2 mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples. METHODS: Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University's Otolaryngology Department, were analyzed for MMP2 expression level, using RNA-in situ hybridization. RESULTS: There were no significant differences in MMP2 mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type (p < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida (p < 0.001). MMP2 mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium. CONCLUSION: Our study reveals that MMP2 mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of MMP2 mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.
OBJECTIVE: Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase-2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed MMP2 mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples. METHODS: Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University's Otolaryngology Department, were analyzed for MMP2 expression level, using RNA-in situ hybridization. RESULTS: There were no significant differences in MMP2 mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type (p < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida (p < 0.001). MMP2 mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium. CONCLUSION: Our study reveals that MMP2 mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of MMP2 mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.
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