The expression of vascular endothelial growth factor is associated with the risk of cancer progression after radical prostatectomy

Peyromaure, Michaël; Camparo, Philippe; Badoual, Cécile; Descazeaud, A.; Dinh-Xuan, Anh Tuan

doi:10.1111/j.1464-410x.2007.06734.x

Cited by 27 publications

(23 citation statements)

References 16 publications

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“…Strong immunohistochemical staining was observed at the periphery of tumor nodules. In our tissue microarray this area might not always be included which could explain this differ- 49,50 In the same line the role and expression pattern of bFGF in the development and progression of PC in the literature is controversial. Cronauer et al 51 reported that bFGF is mainly expressed in carcinomatous areas whereas Trojan et al 52 found a significantly stronger expression in non-tumerous tissue compared with carcinoma.…”

Section: Discussionmentioning

confidence: 98%

Matrix Metalloproteinases and Angiogenic Factors

Boxler

Djonov

Kessler

et al. 2010

The American Journal of Pathology

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The aim of the present study was to investigate whether biomarkers improve the prediction of recurrence-free, disease-specific, and overall survival in patients with clinically localized prostate cancer. A tissue microarray was constructed from prostate specimens of 278 patients who underwent open radical retropubic prostatectomy for clinically localized prostate cancer. For immunohistochemical studies, antibodies were used against matrix metalloproteinase (MMP)؊2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19, as well as against vascular endothelial growth factor, hypoxiainduced factor 1␣, basic fibroblast growth factor, and cluster of differentiation 31. Univariate and multivariable analyses were performed to evaluate the potential predictors of overall, disease-specific, and recurrence-free survival. In univariate analysis of patients with clinically organ-confined prostate cancer, only higher expression levels of MMP-9 (hazard ratio [0.6], 95% CI 0.45؊0.8) had a protective effect in terms of overall survival. This positive effect of high MMP-9 expression was also observed for recurrence-free (HR 0.88, 95% CI 0.78؊0.99) and disease-specific survival (HR 0.5, 95% CI 0.36؊0.73). In multivariable analysis, none of these potential markers was found to be an independent prognostic factor of survival. Of all MMPs and angiogenic factors tested, MMP-9 expression has the potential as a prognostic marker in patients undergoing radical prostatectomy for clinically organ-confined cases of prostate cancer. Prostate cancer (PC) is one of the leading causes of cancer death in men and represents a major burden for any health care system. 1 Radical prostatectomy is an accepted treatment option for patients with organ-confined disease and a life expectancy of Ͼ10 years. Radical prostatectomy has been shown to reduce overall and disease-specific mortality, and the risks of metastasis and local progression.2 Although radical prostatectomy is one of the most common major surgical procedures in many Western countries, it remains unclear who would most likely benefit from this operation.Prostate cancer progression depends on matrix metalloproteinases (MMPs) and angiogenic factors 3 . 4Screening has been shown to decrease mortality, but with a high risk of overdetection and overtreatment. 5Therefore there is a dire need for new prognostic markers. Matrix metalloproteinases are involved in many physiological and pathological processes. In cancer, MMPs play an important role by extracellular remodeling in tumor progression and metastases and have gained in interest. 6 MMPs are also important for tumor angiogenesis, which is a key factor for tumor cell survival. Thus, we investigated selected MMPs (MMP-2, Ϫ3, Ϫ7, Ϫ9, Ϫ13, Ϫ19) and angiogenic factors (vascular endothelial growth factor [VEGF], hypoxia-induced factor 1␣ [HIF 1␣], basic fibroblast growth factor[bFGF ]) as well as the intratumoral microvessel density (IMD) in prostate cancer as predictors for survival and recurrence in men with clinically organ confined prostate cancer using a t...

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Section: Discussionmentioning

confidence: 98%

Matrix Metalloproteinases and Angiogenic Factors

Boxler

Djonov

Kessler

et al. 2010

The American Journal of Pathology

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“…Recently, some studies have explored its prognostic significance in prostate cancer (19)(20)(21)(22)(23). Furthermore, tissue hypoxia is also a critical factor during the establishment of tumor angiogenesis and has been associated with increased tumor cell migration, metastasis, and poor patient outcome (24,25).…”

Section: Introductionmentioning

confidence: 99%

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

Gravdal¹,

Halvorsen²,

Haukaas

et al. 2009

Cancer Research

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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-1A (HIF-1A) 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-1A. 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-1A 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-1A expression. These novel data might have an effect on clinical evaluation and treatment of prostate cancer patients. [Cancer Res 2009;69(11):4708-15]

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“…El patrón de marcaje de VEGF es controversial como factor pronóstico para la evolución del CaP [21][22][23][24][25] , pero podría ser de utilidad en el diagnósti-co diferencial entre HPB y CaP cuando las biopsias sean dudosas, ya que el patrón de marcaje de VEGF de las células glandulares es diferente entre la cé-lulas malignas y las hiperplásicas (Figuras 1 y 2).…”

Section: Discussionunclassified