Coexpression of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in Wilms' tumor

John Karth, Fernando A. Ferrer, Elizabeth Perlman, Collen Hanrahan, Jonathan W. Simons, John P. Gearhart, Ronald Rodriguez

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background/Purpose: Hypoxia-inducible factor 1 alpha (HIF-1α) is an important transcriptional factor responsible for regulating expression of the angiogenic cytokine, vascular endothelial growth factor (VEGF). Little information is available regarding factors involved in the hypoxic cascade, such as HIF or VEGF in Wilms' tumor. We concomitantly evaluate the expression of HIF-1α and VEGF in ex vivo human Wilms' tumor specimens. Methods: Immunohistochemical analysis (IHC) utilizing a monoclonal human anti-HIF-1α or a polyclonal anti-VEGF antibody was performed on ex vivo specimens of Wilms' tumor (n = 18). Predominant tumor histologic subtype was divided equally between epithelial (n = 6), blastemal (n = 6), and mixed (n = 6). Specimens were scored on a predetermined scale for distribution (percent positive cells) and intensity of HIF-1α/VEGF expression within areas of tumor. Results: IHC analysis found that HIF-1α and VEGF were expressed in all Wilms' tumor specimens. Strong nuclear staining for HIF-1α was seen in all samples evaluated, (n = 18), mean score 2.7 (>50% cells exhibiting nuclear HIF-1α expression). Cytoplasmic staining for HIF-1α also was seen in 15 of 18 samples (83%). Distribution of VEGF was equivalent between blastemal and epthelial components, mean score 2.23 versus 2.35. Conclusions: HIF-1α and one of its regulatory end-products, the angiogenic cytokine VEGF, are simultaneously expressed in human Wilms' tumor. In Wilms' tumor, intratumoral hypoxia may stimulate tumor conversion to the angiogenic phenotype and incite production of VEGF. Strategies targeting the hypoxic cascade ultimately may prove efficacious against Wilms' tumor. Copyright (C) 2000 by W.B. Saunders Company.

Original languageEnglish (US)
Pages (from-to)1749-1753
Number of pages5
JournalJournal of Pediatric Surgery
Volume35
Issue number12
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Wilms Tumor
Vascular Endothelial Growth Factor A
Staining and Labeling
Cytokines
Cell Hypoxia
Neoplasms
Phenotype

Keywords

  • Hypoxia inducible factor
  • Vascular endothelial growth factor
  • Wilms' tumor

ASJC Scopus subject areas

  • Surgery

Cite this

Coexpression of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in Wilms' tumor. / Karth, John; Ferrer, Fernando A.; Perlman, Elizabeth; Hanrahan, Collen; Simons, Jonathan W.; Gearhart, John P.; Rodriguez, Ronald.

In: Journal of Pediatric Surgery, Vol. 35, No. 12, 2000, p. 1749-1753.

Research output: Contribution to journalArticle

Karth, John ; Ferrer, Fernando A. ; Perlman, Elizabeth ; Hanrahan, Collen ; Simons, Jonathan W. ; Gearhart, John P. ; Rodriguez, Ronald. / Coexpression of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in Wilms' tumor. In: Journal of Pediatric Surgery. 2000 ; Vol. 35, No. 12. pp. 1749-1753.
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abstract = "Background/Purpose: Hypoxia-inducible factor 1 alpha (HIF-1α) is an important transcriptional factor responsible for regulating expression of the angiogenic cytokine, vascular endothelial growth factor (VEGF). Little information is available regarding factors involved in the hypoxic cascade, such as HIF or VEGF in Wilms' tumor. We concomitantly evaluate the expression of HIF-1α and VEGF in ex vivo human Wilms' tumor specimens. Methods: Immunohistochemical analysis (IHC) utilizing a monoclonal human anti-HIF-1α or a polyclonal anti-VEGF antibody was performed on ex vivo specimens of Wilms' tumor (n = 18). Predominant tumor histologic subtype was divided equally between epithelial (n = 6), blastemal (n = 6), and mixed (n = 6). Specimens were scored on a predetermined scale for distribution (percent positive cells) and intensity of HIF-1α/VEGF expression within areas of tumor. Results: IHC analysis found that HIF-1α and VEGF were expressed in all Wilms' tumor specimens. Strong nuclear staining for HIF-1α was seen in all samples evaluated, (n = 18), mean score 2.7 (>50{\%} cells exhibiting nuclear HIF-1α expression). Cytoplasmic staining for HIF-1α also was seen in 15 of 18 samples (83{\%}). Distribution of VEGF was equivalent between blastemal and epthelial components, mean score 2.23 versus 2.35. Conclusions: HIF-1α and one of its regulatory end-products, the angiogenic cytokine VEGF, are simultaneously expressed in human Wilms' tumor. In Wilms' tumor, intratumoral hypoxia may stimulate tumor conversion to the angiogenic phenotype and incite production of VEGF. Strategies targeting the hypoxic cascade ultimately may prove efficacious against Wilms' tumor. Copyright (C) 2000 by W.B. Saunders Company.",
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T1 - Coexpression of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in Wilms' tumor

AU - Karth, John

AU - Ferrer, Fernando A.

AU - Perlman, Elizabeth

AU - Hanrahan, Collen

AU - Simons, Jonathan W.

AU - Gearhart, John P.

AU - Rodriguez, Ronald

PY - 2000

Y1 - 2000

N2 - Background/Purpose: Hypoxia-inducible factor 1 alpha (HIF-1α) is an important transcriptional factor responsible for regulating expression of the angiogenic cytokine, vascular endothelial growth factor (VEGF). Little information is available regarding factors involved in the hypoxic cascade, such as HIF or VEGF in Wilms' tumor. We concomitantly evaluate the expression of HIF-1α and VEGF in ex vivo human Wilms' tumor specimens. Methods: Immunohistochemical analysis (IHC) utilizing a monoclonal human anti-HIF-1α or a polyclonal anti-VEGF antibody was performed on ex vivo specimens of Wilms' tumor (n = 18). Predominant tumor histologic subtype was divided equally between epithelial (n = 6), blastemal (n = 6), and mixed (n = 6). Specimens were scored on a predetermined scale for distribution (percent positive cells) and intensity of HIF-1α/VEGF expression within areas of tumor. Results: IHC analysis found that HIF-1α and VEGF were expressed in all Wilms' tumor specimens. Strong nuclear staining for HIF-1α was seen in all samples evaluated, (n = 18), mean score 2.7 (>50% cells exhibiting nuclear HIF-1α expression). Cytoplasmic staining for HIF-1α also was seen in 15 of 18 samples (83%). Distribution of VEGF was equivalent between blastemal and epthelial components, mean score 2.23 versus 2.35. Conclusions: HIF-1α and one of its regulatory end-products, the angiogenic cytokine VEGF, are simultaneously expressed in human Wilms' tumor. In Wilms' tumor, intratumoral hypoxia may stimulate tumor conversion to the angiogenic phenotype and incite production of VEGF. Strategies targeting the hypoxic cascade ultimately may prove efficacious against Wilms' tumor. Copyright (C) 2000 by W.B. Saunders Company.

AB - Background/Purpose: Hypoxia-inducible factor 1 alpha (HIF-1α) is an important transcriptional factor responsible for regulating expression of the angiogenic cytokine, vascular endothelial growth factor (VEGF). Little information is available regarding factors involved in the hypoxic cascade, such as HIF or VEGF in Wilms' tumor. We concomitantly evaluate the expression of HIF-1α and VEGF in ex vivo human Wilms' tumor specimens. Methods: Immunohistochemical analysis (IHC) utilizing a monoclonal human anti-HIF-1α or a polyclonal anti-VEGF antibody was performed on ex vivo specimens of Wilms' tumor (n = 18). Predominant tumor histologic subtype was divided equally between epithelial (n = 6), blastemal (n = 6), and mixed (n = 6). Specimens were scored on a predetermined scale for distribution (percent positive cells) and intensity of HIF-1α/VEGF expression within areas of tumor. Results: IHC analysis found that HIF-1α and VEGF were expressed in all Wilms' tumor specimens. Strong nuclear staining for HIF-1α was seen in all samples evaluated, (n = 18), mean score 2.7 (>50% cells exhibiting nuclear HIF-1α expression). Cytoplasmic staining for HIF-1α also was seen in 15 of 18 samples (83%). Distribution of VEGF was equivalent between blastemal and epthelial components, mean score 2.23 versus 2.35. Conclusions: HIF-1α and one of its regulatory end-products, the angiogenic cytokine VEGF, are simultaneously expressed in human Wilms' tumor. In Wilms' tumor, intratumoral hypoxia may stimulate tumor conversion to the angiogenic phenotype and incite production of VEGF. Strategies targeting the hypoxic cascade ultimately may prove efficacious against Wilms' tumor. Copyright (C) 2000 by W.B. Saunders Company.

KW - Hypoxia inducible factor

KW - Vascular endothelial growth factor

KW - Wilms' tumor

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