Department of Otorhinolaryngology, Aichi Medical University School of Medicine, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
Department of Otorhinolaryngology, Nagoya Ekisaikai Hospital, 4-66, Shonencho, 11 Nakagawa-ku, Nagoya, Aichi 454-0854, Japan.
Biomed Res Int. 2021 Mar 10;2021:6644897. doi: 10.1155/2021/6644897. eCollection 2021.
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 mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples.
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.
There were no significant differences in 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 ( < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida ( < 0.001). mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium.
Our study reveals that mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.
胆脂瘤是一种临床表现差异较大的疾病,部分患者可出现自发性消退,而部分患者则表现为侵袭性致死性疾病。儿童胆脂瘤可分为先天性和后天性两类。识别良好的预后标志物有助于选择需要立即手术干预的患者。基质金属蛋白酶-2(MMP2)先前被报道在胆脂瘤进展中发挥重要作用,通过促进骨质破坏和角质形成细胞浸润。在此,我们使用福尔马林固定石蜡包埋(FFPE)组织样本中的 RNA 原位杂交技术分析了胆脂瘤中 MMP2 的 mRNA 表达水平。
对在爱知医科大学耳鼻喉科接受初次手术的 60 名 15 岁以下胆脂瘤患者进行了 MMP2 表达水平的 RNA 原位杂交分析。
先天性胆脂瘤和后天性胆脂瘤之间 MMP2 的 mRNA 表达水平无显著差异。在先天性胆脂瘤中,开放型的 MMP2 信号高于闭合型(<0.001)。在后天性胆脂瘤中,紧张部的 MMP2 信号高于松弛部(<0.001)。MMP2 的 mRNA 表达水平几乎仅存在于成纤维细胞或基质中的炎症细胞中,而不存在于上皮细胞中。
本研究表明 MMP2 的 mRNA 表达水平与胆脂瘤的亚型密切相关。这些发现提示 MMP2 的表达水平可能与胆脂瘤的发病机制和侵袭性特征有关。