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缺氧诱导因子-1α(HIF-1α)在垂体肿瘤中的表达

Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in pituitary tumours.

作者信息

Vidal S, Horvath E, Kovacs K, Kuroki T, Lloyd R V, Scheithauer B W

机构信息

Department of Anatomy, Laboratory of Histology, University of Santiago de Compostela, Lugo, Spain.

出版信息

Histol Histopathol. 2003 Jul;18(3):679-86. doi: 10.14670/HH-18.679.

Abstract

The present study was performed to investigate HIF-1alpha (hypoxia-inducible factor-1alpha) expression in a large number of immunohistochemically and ultrastructurally characterized surgically removed pituitary tumours. The potential relation of HIF-1alpha with outcome variables as well as the presence of HIF-1alpha expression in the tumours treated with dopamine agonists and octreotide, a long-acting somatostatin analogue was also investigated. HIF-1alpha immunoreactivity was confined to the nucleoplasm whereas the nucleoli were unconspicuous. The distribution of HIF-1alpha was evident in the tumours whereas normal adenohypophysial cells showed no HIF-1alpha staining. HIF-1alpha expression was detected not only in the tumour cells but also in endothelial cells lining the blood vessels within the tumour. ACTH producing adenomas showed the lowest level of HIF-1alpha expression whereas pituitary carcinomas and GH producing adenomas had the highest counts. The statistical study demonstrated no significant correlation between HIF-1alpha expression, patient age, gender, tumour, size, invasiveness, cell proliferation rate and vascularity. These results suggest that the behaviour of pituitary tumours does not primarily depend of HIF-1alpha expression. Our study demonstrated an increase HIF-1alpha expression in bromocriptine treated PRL producing pituitary adenomas compared with untreated tumours but no increase in octreotide treated tumours.

摘要

本研究旨在通过免疫组织化学和超微结构对大量手术切除的垂体肿瘤进行特征分析,以研究缺氧诱导因子-1α(HIF-1α)的表达情况。同时,还研究了HIF-1α与预后变量之间的潜在关系,以及多巴胺激动剂和长效生长抑素类似物奥曲肽治疗的肿瘤中HIF-1α表达的情况。HIF-1α免疫反应性局限于核质,而核仁不明显。HIF-1α的分布在肿瘤中很明显,而正常腺垂体细胞未显示HIF-1α染色。不仅在肿瘤细胞中检测到HIF-1α表达,在肿瘤内血管内衬的内皮细胞中也检测到。促肾上腺皮质激素分泌腺瘤的HIF-1α表达水平最低,而垂体癌和生长激素分泌腺瘤的计数最高。统计学研究表明,HIF-1α表达与患者年龄、性别、肿瘤大小、侵袭性、细胞增殖率和血管形成之间无显著相关性。这些结果表明,垂体肿瘤的行为并不主要取决于HIF-1α的表达。我们的研究表明,与未治疗的肿瘤相比,溴隐亭治疗的泌乳素分泌型垂体腺瘤中HIF-1α表达增加,但奥曲肽治疗的肿瘤中未增加。

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