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缺氧诱导因子-2α在口腔黏膜下纤维化恶变中的表达研究

Study of Hypoxia-inducible factor-2α expression in the malignant transformation of Oral submucous fibrosis.

作者信息

Joseph Immanuel, Elizabeth Joshua, Rao Umadevi K, Ranganathan Kannan

机构信息

Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospital, Chennai, Tamil Nadu, India.

出版信息

J Oral Maxillofac Pathol. 2020 Jan-Apr;24(1):33-39. doi: 10.4103/jomfp.JOMFP_42_19. Epub 2020 May 8.

DOI:10.4103/jomfp.JOMFP_42_19
PMID:32508445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7269270/
Abstract

CONTEXT

Hypoxia-inducible factor (HIF)-2α is overexpressed in primary and metastatic human cancers, whose expression is correlated with tumor angiogenesis and patient mortality. HIF plays a role in the progression of fibrosis in oral submucous fibrosis (OSF).

AIM AND OBJECTIVE

The aim is to study and compare the expression of HIF-2α in OSF (a), oral squamous cell carcinoma (OSCC) with areca nut usage (b), OSCC without areca nut usage (c) and normal mucosa (d) by immunohistochemistry.

SUBJECTS AND METHODS

Immunohistochemical detection of HIF-2α was done on 51 samples, which included 11 cases (a), 15 cases (b), 15 cases (c) and the expression was compared with that of (d).

STATISTICAL ANALYSIS

Data were analyzed using the SPSS™ software (ver. 21.0). Chi-square test and kappa analysis were performed to compare the intensity of staining between the groups and for inter-observer agreement, respectively. Value of ≤ 0.05 was considered statistically significant. The mean labeling index between the groups was studied by the Kruskal-Wallis test.

RESULTS

All the cases of (d), (a), (b) and (c) showed HIF-2α expression ( = 0.329). About 13% cases of (c) showed intense expression ( = 0.406) and 27% of (a) cases showed expression only in the connective tissue ( = 0.023). The number of positively stained nuclei in both (b and c) cases reduced as the tumor progression was from well to poorly differentiated.

CONCLUSION

Areca nut initiates fibrosis and subsequent hypoxia in OSF which triggers HIF-2α expression in the epithelium. HIF-2α could be a surrogate marker for cancer initiation and progression.

摘要

背景

缺氧诱导因子(HIF)-2α在原发性和转移性人类癌症中过度表达,其表达与肿瘤血管生成和患者死亡率相关。HIF在口腔黏膜下纤维化(OSF)的纤维化进展中起作用。

目的

通过免疫组织化学研究并比较HIF-2α在OSF(a)、有槟榔使用史的口腔鳞状细胞癌(OSCC)(b)、无槟榔使用史的OSCC(c)和正常黏膜(d)中的表达。

对象与方法

对51个样本进行HIF-2α的免疫组织化学检测,其中包括11例(a)、15例(b)、15例(c),并将其表达与(d)的表达进行比较。

统计分析

使用SPSS™软件(版本21.0)分析数据。分别进行卡方检验和kappa分析,以比较组间染色强度和观察者间的一致性。P≤0.05的值被认为具有统计学意义。通过Kruskal-Wallis检验研究组间的平均标记指数。

结果

所有(d)、(a)、(b)和(c)病例均显示HIF-2α表达(P = 0.329)。约13%的(c)病例显示强表达(P = 0.406),27%的(a)病例仅在结缔组织中显示表达(P = 0.023)。随着肿瘤从高分化向低分化进展,(b和c)病例中阳性染色细胞核的数量减少。

结论

槟榔引发OSF中的纤维化和随后的缺氧,从而触发上皮细胞中HIF-2α的表达。HIF-2α可能是癌症发生和进展的替代标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c71/7269270/b9c65f63f300/JOMFP-24-33-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c71/7269270/fa3cc02fbee3/JOMFP-24-33-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c71/7269270/b9c65f63f300/JOMFP-24-33-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c71/7269270/fa3cc02fbee3/JOMFP-24-33-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c71/7269270/b9c65f63f300/JOMFP-24-33-g003.jpg

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