TY - JOUR
T1 - Angiogenesis in vestibular schwannomas
T2 - expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1
AU - Møller, Martin Nue
AU - Werther, Kim
AU - Nalla, Amarnadh
AU - Stangerup, Sven-Eric
AU - Thomsen, Jens
AU - Bøg-Hansen, Thorkild C
AU - Nielsen, Hans Jørgen
AU - Cayé-Thomasen, Per
PY - 2010/4
Y1 - 2010/4
N2 - Objectives/Hypothesis: Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study targets the angiogenic process by investigation of tumor expression of MMP- 2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored. Study Design: Prospective vestibular schwannoma tissue sampling for ELISA and immunohistochemical determination of MMP-2, MMP-9 and TIMP-1. Methods: Thirty-four patients with a sporadic, noncystic, vestibular schwannoma were selected prospectively. Repeated, preoperative magnetic resonance imaging determined the tumor growth pattern. Following translabyrinthine resection, an enzyme-linked immunosorbent assay was used for determination of the MMP-2, MMP-9, and TIMP-1 concentration in tumor sample homogenates. Immunohistochemical labeling was performed in 12 randomly selected tumors. Results: All tumor homogenates expressed measurable MMP-9, MMP-2, and TIMP-1. Immunolabeling localized MMP-9 expression to the tumor cells, whereas MMP-2 and TIMP-1 was found interstitially. A significant correlation existed between the concentration MMP-9 and absolute tumor growth rate, whereas a weak correlation occurred for the relative growth rate. Conclusions: Vestibular schwannomas express MMP-2, MMP-9, and TIMP-1 and the tumor concentration of MMP-9 correlates with absolute tumor growth rate, but not with age, gender, symptom duration, or preoperative tumor size. No correlations existed between any clinical parameter and MMP-2 or TIMP-1 expression. We conclude that MMP-9 appears to be involved in the growth of vestibular schwannomas.
AB - Objectives/Hypothesis: Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study targets the angiogenic process by investigation of tumor expression of MMP- 2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored. Study Design: Prospective vestibular schwannoma tissue sampling for ELISA and immunohistochemical determination of MMP-2, MMP-9 and TIMP-1. Methods: Thirty-four patients with a sporadic, noncystic, vestibular schwannoma were selected prospectively. Repeated, preoperative magnetic resonance imaging determined the tumor growth pattern. Following translabyrinthine resection, an enzyme-linked immunosorbent assay was used for determination of the MMP-2, MMP-9, and TIMP-1 concentration in tumor sample homogenates. Immunohistochemical labeling was performed in 12 randomly selected tumors. Results: All tumor homogenates expressed measurable MMP-9, MMP-2, and TIMP-1. Immunolabeling localized MMP-9 expression to the tumor cells, whereas MMP-2 and TIMP-1 was found interstitially. A significant correlation existed between the concentration MMP-9 and absolute tumor growth rate, whereas a weak correlation occurred for the relative growth rate. Conclusions: Vestibular schwannomas express MMP-2, MMP-9, and TIMP-1 and the tumor concentration of MMP-9 correlates with absolute tumor growth rate, but not with age, gender, symptom duration, or preoperative tumor size. No correlations existed between any clinical parameter and MMP-2 or TIMP-1 expression. We conclude that MMP-9 appears to be involved in the growth of vestibular schwannomas.
KW - Adult
KW - Aged
KW - Enzyme-Linked Immunosorbent Assay
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Immunohistochemistry
KW - Magnetic Resonance Imaging
KW - Male
KW - Matrix Metalloproteinase 2
KW - Matrix Metalloproteinase 9
KW - Middle Aged
KW - Neoplasm Staging
KW - Neovascularization, Pathologic
KW - Neuroma, Acoustic
KW - Prospective Studies
KW - RNA, Neoplasm
KW - Tissue Inhibitor of Metalloproteinase-1
U2 - 10.1002/lary.20834
DO - 10.1002/lary.20834
M3 - Journal article
C2 - 20205165
SN - 0023-852X
VL - 120
SP - 657
EP - 662
JO - Laryngoscope
JF - Laryngoscope
IS - 4
ER -