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缺氧诱导因子-1α和半胱氨酸天冬氨酸蛋白酶-3在牙源性囊肿和肿瘤囊变中的作用。

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors.

机构信息

Cell Culture Laboratory, School of Dentistry, Federal University of Pará, Rua Augusto Corrêa, 01, Guamá, Belém, PA, 66075110, Brazil.

School of Dentistry, Universidade Positivo, Av. Prof. Pedro Viriato Parigot de Souza, 5300, Curitiba, PR, 80740-050, Brazil.

出版信息

Clin Oral Investig. 2018 Jan;22(1):141-149. doi: 10.1007/s00784-017-2090-6. Epub 2017 Feb 25.

Abstract

OBJECTIVES

Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIF-1α), a responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors.

MATERIAL AND METHODS

Twenty cases of ameloblastoma, keratocystic odontogenic tumor (KOT) (n = 20), radicular cyst (RC) (n = 18), dentigerous cyst (DC) (n = 11), calcifying cystic odontogenic tumor (n = 8), and dental follicle (DF) (n = 10) were used to investigate HIF-1α and caspase-3 expression in sequential serial cuts by immunohistochemistry.

RESULTS

HIF-1α was overexpressed in RC, DC, and ameloblastoma when compared with DF. The basal and sometimes the lower suprabasal layer showed no or very low expression in DC, KOT, and ameloblastoma, the last also showing strong expression in solid epithelial areas and initial cystic formation regions. Caspase-3 was found to be overexpressed in all lesions, with the highest expression in odontogenic cysts compared to tumors. HIF-1α and caspase-3 were localized in similar areas of the same lesions, especially in the epithelium surrounding cystic formations.

CONCLUSIONS

This study showed distinct immunoexpression of HIF-1α and caspase-3 in odontogenic cyst and tumors, with higher expression observed in odontogenic cysts.

CLINICAL RELEVANCE

These findings suggest a possible correlation between hypoxia, apoptosis, and cystogenesis, leading to understand the mechanisms responsible to cystic formation in odontogenic lesions.

摘要

目的

牙源性囊肿和肿瘤是最常见的颌骨病变。这些病变的共同特征是形成囊状区域,这种共同特征可能提示涉及类似的机制。缺氧诱导因子 1 阿尔法(HIF-1α)是一种对缺氧有反应的蛋白质,半胱氨酸天冬氨酸蛋白酶-3(caspase-3)是一种不可逆的凋亡标志物,可能有助于囊形成。因此,本研究旨在研究牙源性囊肿和肿瘤中这些蛋白质的免疫表达。

材料和方法

使用 20 例造釉细胞瘤、角化囊肿性牙源性肿瘤(KOT)(n=20)、根囊肿(RC)(n=18)、含牙囊肿(DC)(n=11)、牙源性钙化囊性瘤(n=8)和牙滤泡(DF)(n=10),通过免疫组织化学法研究 HIF-1α 和 caspase-3 在连续切片中的表达。

结果

与 DF 相比,RC、DC 和造釉细胞瘤中 HIF-1α 过度表达。在 DC、KOT 和造釉细胞瘤中,基底和有时下基层显示无或极低表达,最后也在实性上皮区域和初始囊形成区域显示强表达。在所有病变中均发现 caspase-3 过度表达,牙源性囊肿的表达高于肿瘤。HIF-1α 和 caspase-3 定位于同一病变的相似区域,尤其是在围绕囊形成的上皮周围。

结论

本研究显示牙源性囊肿和肿瘤中 HIF-1α 和 caspase-3 的免疫表达不同,牙源性囊肿的表达较高。

临床意义

这些发现表明缺氧、凋亡和囊发生之间可能存在相关性,从而有助于理解牙源性病变中囊形成的机制。

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