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Proteins involved in regulating bone invasion in skull base meningiomas.

Salehi F, Jalali S, Alkins R, Lee JI, Lwu S, Burrell K, Gentili F, Croul S, Zadeh G - Acta Neurochir (Wien) (2012)

Bottom Line: Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1).MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells.We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 4W-439, Toronto, ON, M5T 2S8, Canada. fsalehi@uwo.ca

ABSTRACT

Background: Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion.

Methods: Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations.

Results: MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas.

Conclusions: We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.

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Immunohistochemical expression of MMP2, OPN, and ITGB1 in bone invasive and noninvasive meningiomas (original magnification ×400). a Low vascular MMP immunoexpression in a bone-invading transbasal meningioma. b High vascular MMP immunoreactivity in a noninvading skull base meningioma. The arrows indicate vascular immunostaining. c Low vascular OPN immunoexpression in a noninvading skull base meningioma. d High vascular OPN immunopositivity in a bone-invading transbasal meningioma. The arrows indicate vascular immunostaining. e Low tumoral ITGB1 immunoreactivity in a noninvading skull base meningioma. f High tumoral ITGB1 immunoexpression in a bone-invading transbasal meningioma. g Low vascular ITGB1 immunopositivity in a noninvading skull base meningioma. h High vascular ITGB1 immunoreactivity in a bone-invading transbasal meningioma in multiple layers extending from the endothelium through the media and into the adventitia. The arrows indicate vascular immunostaining
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Fig1: Immunohistochemical expression of MMP2, OPN, and ITGB1 in bone invasive and noninvasive meningiomas (original magnification ×400). a Low vascular MMP immunoexpression in a bone-invading transbasal meningioma. b High vascular MMP immunoreactivity in a noninvading skull base meningioma. The arrows indicate vascular immunostaining. c Low vascular OPN immunoexpression in a noninvading skull base meningioma. d High vascular OPN immunopositivity in a bone-invading transbasal meningioma. The arrows indicate vascular immunostaining. e Low tumoral ITGB1 immunoreactivity in a noninvading skull base meningioma. f High tumoral ITGB1 immunoexpression in a bone-invading transbasal meningioma. g Low vascular ITGB1 immunopositivity in a noninvading skull base meningioma. h High vascular ITGB1 immunoreactivity in a bone-invading transbasal meningioma in multiple layers extending from the endothelium through the media and into the adventitia. The arrows indicate vascular immunostaining

Mentions: MMP2 was expressed to a variable degree in tumor cell cytoplasm and the immunoscores of MMP2 tumor expression showed no significant difference between spheno-orbital tumors and the control sphenoid wing tumors and between transbasal and anterior skull base control meningiomas (Table 2). MMP2 expression within tumor vessels was restricted to the endothelium and did not involve the media or adventitia (Table 2). There was significantly lower vascular immunoexpression by bone-invasive transbasal tumors compared to control anterior skull base (p = 0.004 one-tailed) (Fig. 1a, b).Table 2


Proteins involved in regulating bone invasion in skull base meningiomas.

Salehi F, Jalali S, Alkins R, Lee JI, Lwu S, Burrell K, Gentili F, Croul S, Zadeh G - Acta Neurochir (Wien) (2012)

Immunohistochemical expression of MMP2, OPN, and ITGB1 in bone invasive and noninvasive meningiomas (original magnification ×400). a Low vascular MMP immunoexpression in a bone-invading transbasal meningioma. b High vascular MMP immunoreactivity in a noninvading skull base meningioma. The arrows indicate vascular immunostaining. c Low vascular OPN immunoexpression in a noninvading skull base meningioma. d High vascular OPN immunopositivity in a bone-invading transbasal meningioma. The arrows indicate vascular immunostaining. e Low tumoral ITGB1 immunoreactivity in a noninvading skull base meningioma. f High tumoral ITGB1 immunoexpression in a bone-invading transbasal meningioma. g Low vascular ITGB1 immunopositivity in a noninvading skull base meningioma. h High vascular ITGB1 immunoreactivity in a bone-invading transbasal meningioma in multiple layers extending from the endothelium through the media and into the adventitia. The arrows indicate vascular immunostaining
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569595&req=5

Fig1: Immunohistochemical expression of MMP2, OPN, and ITGB1 in bone invasive and noninvasive meningiomas (original magnification ×400). a Low vascular MMP immunoexpression in a bone-invading transbasal meningioma. b High vascular MMP immunoreactivity in a noninvading skull base meningioma. The arrows indicate vascular immunostaining. c Low vascular OPN immunoexpression in a noninvading skull base meningioma. d High vascular OPN immunopositivity in a bone-invading transbasal meningioma. The arrows indicate vascular immunostaining. e Low tumoral ITGB1 immunoreactivity in a noninvading skull base meningioma. f High tumoral ITGB1 immunoexpression in a bone-invading transbasal meningioma. g Low vascular ITGB1 immunopositivity in a noninvading skull base meningioma. h High vascular ITGB1 immunoreactivity in a bone-invading transbasal meningioma in multiple layers extending from the endothelium through the media and into the adventitia. The arrows indicate vascular immunostaining
Mentions: MMP2 was expressed to a variable degree in tumor cell cytoplasm and the immunoscores of MMP2 tumor expression showed no significant difference between spheno-orbital tumors and the control sphenoid wing tumors and between transbasal and anterior skull base control meningiomas (Table 2). MMP2 expression within tumor vessels was restricted to the endothelium and did not involve the media or adventitia (Table 2). There was significantly lower vascular immunoexpression by bone-invasive transbasal tumors compared to control anterior skull base (p = 0.004 one-tailed) (Fig. 1a, b).Table 2

Bottom Line: Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1).MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells.We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 4W-439, Toronto, ON, M5T 2S8, Canada. fsalehi@uwo.ca

ABSTRACT

Background: Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion.

Methods: Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations.

Results: MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas.

Conclusions: We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.

Show MeSH
Related in: MedlinePlus