Journal article
Constitutive Expression of HIF-α Plays a Major Role in Generation of Clear Cell Phenotype in Human Primary and Metastatic Renal Carcinoma
Applied immunohistochemistry & molecular morphology, Vol.22(9), pp.642-647
10/01/2014
DOI: 10.1097/PAI.0000000000000012
PMCID: PMC4184929
PMID: 25046225
Abstract
The extensive lipid accumulation occurred in clear cell renal cell carcinoma (ccRCC) resulted in a clear cell cytoplasm. Hypoxia inducible factor alpha (HIF-α) was constitutively expressed in many ccRCC and transcriptionally regulates greater than one hundred genes. In a recent breakthrough study, HIF-1α induced ccRCC in transgenic mice. Based on these findings, we developed a hypothesis that accounted for HIF-α generation of the clear cell phenotype. The aim of the present study to use immunohistochemical staining methods in tissue microarray (TMA) to determine the extent to which the clear cell phenotype coincided with HIF-α expression in primary and metastatic ccRCC. In addition, we studied whether the prolyl-hydroxylases (PHD2,3) play a role in promoting the elevated expression of HIF-α in tumor cells. The clear cell phenotype was observed in all primary and metastatic cases of ccRCC examined. A total of 168 renal cell carcinomas were evaluated by immunohistochemical methods; 141/168(84%) of tumors expressed HIF-α (HIF-1α and/or HIF-2α). In contrast, HIF-α was expressed in only 1/23 (4%) of non-clear cell renal cell carcinomas. These data supported the hypothesis that in the majority of the tumors HIF-α expression overlapped with the clear cell phenotype, and was indicative of a HIF-α mediated lipid accumulation. In a smaller percentage of ccRCC cases (16%) HIF-α was not detected in the tumor cells and suggested that lipid accumulation by HIF-α -lipid independent process. PHD3 was undetectable in both primary and metastatic ccRCC cases. We concluded that the undetectable PHD3 could contribute to the higher HIF-α expression in ccRCC.
Details
- Title: Subtitle
- Constitutive Expression of HIF-α Plays a Major Role in Generation of Clear Cell Phenotype in Human Primary and Metastatic Renal Carcinoma
- Creators
- Károly Tóth - Roswell Park Cancer InstituteSreenivasulu Chintala - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Applied immunohistochemistry & molecular morphology, Vol.22(9), pp.642-647
- DOI
- 10.1097/PAI.0000000000000012
- PMID
- 25046225
- PMCID
- PMC4184929
- NLM abbreviation
- Appl Immunohistochem Mol Morphol
- ISSN
- 1541-2016
- eISSN
- 1533-4058
- Language
- English
- Date published
- 10/01/2014
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360158702771
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