Proliferation of Immature Tumor Vessels Is a Novel Marker of Clinical Progression in Prostate Cancer

Nestin (neuroepithelial stem cell protein) is expressed in immature endothelial cells, and we here introduce coexpression of Nestin and Ki-67 as a novel angiogenesis marker on tissue sections. Including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1alpha (HIF-1alpha) expr...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 69; no. 11; pp. 4708 - 4715
Main Authors:	GRAUDAL, Karsten, HALVORSEN, Ole J, HAUKAAS, Svein A, AKSLEN, Lars A
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-06-2009
Subjects:	Adenocarcinoma - blood supply Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenocarcinoma - surgery Aged Antineoplastic agents Biological and medical sciences Biomarkers, Tumor - analysis Biomarkers, Tumor - metabolism Blood Vessels - metabolism Blood Vessels - pathology Disease Progression Follow-Up Studies Gynecology. Andrology. Obstetrics Humans Hypoxia-Inducible Factor 1, alpha Subunit - analysis Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Intermediate Filament Proteins - metabolism Ki-67 Antigen - metabolism Male Male genital diseases Medical sciences Middle Aged Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology Nephrology. Urinary tract diseases Nerve Tissue Proteins - metabolism Nestin Orchiectomy Pharmacology. Drug treatments Prostatectomy Prostatic Neoplasms - blood supply Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Prostatic Neoplasms - surgery Treatment Failure Tumors Tumors of the urinary system Urinary tract. Prostate gland Vascular Endothelial Growth Factor A - analysis Vascular Endothelial Growth Factor A - metabolism Cell proliferation Urinary system disease Prostate disease Blood vessel Biological marker Evolution Circulatory system Malignant tumor Immaturity Male genital diseases Prostate cancer Cancer
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Summary:	Nestin (neuroepithelial stem cell protein) is expressed in immature endothelial cells, and we here introduce coexpression of Nestin and Ki-67 as a novel angiogenesis marker on tissue sections. Including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1alpha (HIF-1alpha) expression, we studied relation to disease progression in prostate cancer. Different patient series were included. Sections from 104 radical prostatectomies with long follow-up, 33 castration-resistant prostate cancers, 28 nonskeletal metastases, 13 skeletal metastases, and 41 benign prostatic hyperplasias were immunostained for Nestin/Ki-67, VEGF-A, and HIF-1alpha. Vascular proliferation by Nestin/Ki-67-positive vessels was counted within "hotspot" areas. Median vascular proliferation counts were 4- to 5-fold higher in castration-resistant prostate cancers and metastases versus localized cancers and prostatic hyperplasias (P < 0.0005). Among localized cancers, high vascular proliferation was significantly related to adverse clinicopathologic features and was a strong and independent predictor of biochemical failure (P < 0.005), clinical recurrence (P = 0.005), and skeletal metastasis (P = 0.025) in multivariate analysis. Castration-resistant cancers were characterized by reduced VEGF-A and increased HIF-1alpha expression, and vascular proliferation was associated with reduced patient survival in this group. Thus, vascular proliferation was of independent prognostic importance among prostate cancers. When compared with localized cancers, vascular proliferation was significantly increased in castration-resistant cases and metastatic lesions. The castration-resistant tumors exhibited weak VEGF-A but strong HIF-1alpha expression. These novel data might have an effect on clinical evaluation and treatment of prostate cancer patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0008-5472 1538-7445
DOI:	10.1158/0008-5472.CAN-08-4417