Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes

Martina B O'Keeffe, Andrea Devlin, Alan J Burns, Tom A Gardiner, Ian Logan, David G Hirst, Stephanie McKeown

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    The contribution of endothelial cell growth to angiogenesis has been widely studied; however, the involvement of pericytes is less well documented, especially in human tumors. In this study we aimed to quantify and assess the prognostic significance of pericyte coverage, the extent of hypoxia, and microvessel density (MVD) in normal bladder mucosa and urothelial carcinoma. Antibody to alpha-smooth muscle actin was used to assess the distribution of pericytes (mural/smooth muscle cells) in the microvessels of normal human bladder (n = 4) mucosa and in urothelial carcinoma (n = 47) samples; this was quantitated using microvessel pericyte index (MPI). The MVD was measured using two different methods (n = 47) and hypoxia was assessed using glucose transporter-1 (Glut-1) staining (n = 30). There was a 70% reduction in MPI in urothelial carcinomas compared to normal bladder mucosa (p < 0.0012); MPI did not correlate with tumor stage or grade. Ta and T1 superficial tumors were divided into two groups with a MPI of <15% or >15%. Progression-free survival was significantly shorter for tumors with MPI >15% (p = 0.0036). MVD had no prognostic value using either evaluation method. Glut-1 immunoreactivity was not prognostic in superficial urothelial carcinoma samples. Tumors with a higher MPI showed a greater Glut-1 immunoreactivity (p = 0.0051). Microvessels in urothelial carcinoma have a considerable loss of pericyte coverage compared to normal bladder mucosa. The data from this preliminary study indicate that progression-free survival was shorter in patients whose superficial tumors had higher pericyte coverage of the microvessels. This may be due to increased levels of hypoxia, as demonstrated by a significant increase in Glut-1 staining.
    LanguageEnglish
    Pages93-101
    JournalOncology Research
    Volume17
    Issue number3
    Publication statusPublished - 2008

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    Pericytes
    Microvessels
    Urinary Bladder Neoplasms
    Facilitative Glucose Transport Proteins
    Carcinoma
    Mucous Membrane
    Urinary Bladder
    Disease-Free Survival
    Neoplasms
    Hypoxia
    Staining and Labeling
    Smooth Muscle Myocytes
    Smooth Muscle
    Actins
    Endothelial Cells

    Cite this

    O'Keeffe, M. B., Devlin, A., Burns, A. J., Gardiner, T. A., Logan, I., Hirst, D. G., & McKeown, S. (2008). Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes. Oncology Research, 17(3), 93-101.
    O'Keeffe, Martina B ; Devlin, Andrea ; Burns, Alan J ; Gardiner, Tom A ; Logan, Ian ; Hirst, David G ; McKeown, Stephanie. / Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes. In: Oncology Research. 2008 ; Vol. 17, No. 3. pp. 93-101.
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    title = "Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes",
    abstract = "The contribution of endothelial cell growth to angiogenesis has been widely studied; however, the involvement of pericytes is less well documented, especially in human tumors. In this study we aimed to quantify and assess the prognostic significance of pericyte coverage, the extent of hypoxia, and microvessel density (MVD) in normal bladder mucosa and urothelial carcinoma. Antibody to alpha-smooth muscle actin was used to assess the distribution of pericytes (mural/smooth muscle cells) in the microvessels of normal human bladder (n = 4) mucosa and in urothelial carcinoma (n = 47) samples; this was quantitated using microvessel pericyte index (MPI). The MVD was measured using two different methods (n = 47) and hypoxia was assessed using glucose transporter-1 (Glut-1) staining (n = 30). There was a 70{\%} reduction in MPI in urothelial carcinomas compared to normal bladder mucosa (p < 0.0012); MPI did not correlate with tumor stage or grade. Ta and T1 superficial tumors were divided into two groups with a MPI of <15{\%} or >15{\%}. Progression-free survival was significantly shorter for tumors with MPI >15{\%} (p = 0.0036). MVD had no prognostic value using either evaluation method. Glut-1 immunoreactivity was not prognostic in superficial urothelial carcinoma samples. Tumors with a higher MPI showed a greater Glut-1 immunoreactivity (p = 0.0051). Microvessels in urothelial carcinoma have a considerable loss of pericyte coverage compared to normal bladder mucosa. The data from this preliminary study indicate that progression-free survival was shorter in patients whose superficial tumors had higher pericyte coverage of the microvessels. This may be due to increased levels of hypoxia, as demonstrated by a significant increase in Glut-1 staining.",
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    O'Keeffe, MB, Devlin, A, Burns, AJ, Gardiner, TA, Logan, I, Hirst, DG & McKeown, S 2008, 'Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes', Oncology Research, vol. 17, no. 3, pp. 93-101.

    Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes. / O'Keeffe, Martina B; Devlin, Andrea; Burns, Alan J; Gardiner, Tom A; Logan, Ian; Hirst, David G; McKeown, Stephanie.

    In: Oncology Research, Vol. 17, No. 3, 2008, p. 93-101.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes

    AU - O'Keeffe, Martina B

    AU - Devlin, Andrea

    AU - Burns, Alan J

    AU - Gardiner, Tom A

    AU - Logan, Ian

    AU - Hirst, David G

    AU - McKeown, Stephanie

    PY - 2008

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    N2 - The contribution of endothelial cell growth to angiogenesis has been widely studied; however, the involvement of pericytes is less well documented, especially in human tumors. In this study we aimed to quantify and assess the prognostic significance of pericyte coverage, the extent of hypoxia, and microvessel density (MVD) in normal bladder mucosa and urothelial carcinoma. Antibody to alpha-smooth muscle actin was used to assess the distribution of pericytes (mural/smooth muscle cells) in the microvessels of normal human bladder (n = 4) mucosa and in urothelial carcinoma (n = 47) samples; this was quantitated using microvessel pericyte index (MPI). The MVD was measured using two different methods (n = 47) and hypoxia was assessed using glucose transporter-1 (Glut-1) staining (n = 30). There was a 70% reduction in MPI in urothelial carcinomas compared to normal bladder mucosa (p < 0.0012); MPI did not correlate with tumor stage or grade. Ta and T1 superficial tumors were divided into two groups with a MPI of <15% or >15%. Progression-free survival was significantly shorter for tumors with MPI >15% (p = 0.0036). MVD had no prognostic value using either evaluation method. Glut-1 immunoreactivity was not prognostic in superficial urothelial carcinoma samples. Tumors with a higher MPI showed a greater Glut-1 immunoreactivity (p = 0.0051). Microvessels in urothelial carcinoma have a considerable loss of pericyte coverage compared to normal bladder mucosa. The data from this preliminary study indicate that progression-free survival was shorter in patients whose superficial tumors had higher pericyte coverage of the microvessels. This may be due to increased levels of hypoxia, as demonstrated by a significant increase in Glut-1 staining.

    AB - The contribution of endothelial cell growth to angiogenesis has been widely studied; however, the involvement of pericytes is less well documented, especially in human tumors. In this study we aimed to quantify and assess the prognostic significance of pericyte coverage, the extent of hypoxia, and microvessel density (MVD) in normal bladder mucosa and urothelial carcinoma. Antibody to alpha-smooth muscle actin was used to assess the distribution of pericytes (mural/smooth muscle cells) in the microvessels of normal human bladder (n = 4) mucosa and in urothelial carcinoma (n = 47) samples; this was quantitated using microvessel pericyte index (MPI). The MVD was measured using two different methods (n = 47) and hypoxia was assessed using glucose transporter-1 (Glut-1) staining (n = 30). There was a 70% reduction in MPI in urothelial carcinomas compared to normal bladder mucosa (p < 0.0012); MPI did not correlate with tumor stage or grade. Ta and T1 superficial tumors were divided into two groups with a MPI of <15% or >15%. Progression-free survival was significantly shorter for tumors with MPI >15% (p = 0.0036). MVD had no prognostic value using either evaluation method. Glut-1 immunoreactivity was not prognostic in superficial urothelial carcinoma samples. Tumors with a higher MPI showed a greater Glut-1 immunoreactivity (p = 0.0051). Microvessels in urothelial carcinoma have a considerable loss of pericyte coverage compared to normal bladder mucosa. The data from this preliminary study indicate that progression-free survival was shorter in patients whose superficial tumors had higher pericyte coverage of the microvessels. This may be due to increased levels of hypoxia, as demonstrated by a significant increase in Glut-1 staining.

    M3 - Article

    VL - 17

    SP - 93

    EP - 101

    JO - Oncology Research

    T2 - Oncology Research

    JF - Oncology Research

    SN - 0965-0407

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    ER -

    O'Keeffe MB, Devlin A, Burns AJ, Gardiner TA, Logan I, Hirst DG et al. Investigation of pericytes, hypoxia, and vascularity in bladder tumors: Association with clinical outcomes. Oncology Research. 2008;17(3):93-101.