Expression of hypoxia inducible factor-1α and 2α in genetically distinct early renal cortical tumors

被引:28
作者
Kim, CM
Vocke, C
Torres-Cabala, C
Yang, YF
Schmidt, L
Walther, M
Linehan, WM
机构
[1] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[3] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD USA
关键词
D O I
10.1016/S0022-5347(05)00890-6
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1 alpha and HIF-2 alpha in genetically distinct early renal cortical tumors. Materials and Methods: Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1 alpha and 2 alpha in clear cell renal carcinoma cells. Results: Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1 alpha and HIF-2 alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dube syndrome expressed predominantly HIF-2 alpha with weaker HIF-1 alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1 alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2 alpha. Conclusions: Differential patterns of HIF-1 alpha and HIF-2 alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1 alpha and HIF-2 alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2 alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1 alpha vs HIF-2 alpha is suggested by the distinct subcellular localization pattern of HIF-1 alpha and HIF-2 alpha in clear cell renal carcinoma cells.
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收藏
页码:1908 / 1914
页数:7
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