Association of Cavernous Malformation Within Vestibular Schwannoma: Immunohistochemical Analysis of Matrix Metalloproteinase-2 and -9  -Case Report-

Sakata, Hiroyuki; Fujimura, Miki; Watanabe, Mika; Tominaga, Teiji

doi:10.2176/nmc.47.509

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…MMP2 is a type IV collagenase and is secreted as a zymogen, which is then proteolytically processed to the active form, which contributes to degradation and damage of the extracellular matrix and basement membrane. Therefore, this promotes tumor cell infiltration of the surrounding tissues by breaking through the basement membrane, ultimately leading to tumor cell invasion and metastasis ( 6 , 7 ). Previous studies have indicated that MMP2 is expressed in a variety of tumor cells, and is associated with tumor cell growth, invasion and metastasis ( 2 , 11 ).…”

Section: Discussionmentioning

confidence: 99%

Expression and significance of MMP2 and HIF-1α in hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is a serious threat to human health. HCC is a malignant tumor and its invasion and metastasis are the result of multigene interactions. Matrix metalloproteinase-2 (MMP-2) is capable of degrading the majority of components of the extracellular matrix and is regarded to closely correlate with tumor invasion and metastasis. Furthermore, the hypoxia-inducible factor 1α (HIF-1α) is an important transcription factor, which is closely associated with the process of tumor growth. The aim of the present study was to investigate the expression of MMP2 and HIF-1α) in HCC, and the relationship between MMP2/HIF-1α protein expression and the clinical/pathological characteristics of HCC. The mRNA levels of MMP2 and HIF-1α were detected in 32 cases of HCC and the corresponding normal adjacent tissues with fluorescence-based quantitative polymerase chain reaction (qPCR). The protein expression of MMP2 and HIF-1α was assessed in 45 HCC cases and 33 cases of corresponding normal adjacent tissue, using immunohistochemical methods. The association between MMP2/HIF-1α and pathological features of HCC, and the correlation between MMP2 and HIF-1α were analyzed. The Kaplan-Meier method was used to assess the impact of MMP2 and HIF-1α expression on survival. The fluorescence-based qPCR demonstrated that MMP2 and HIF-1α mRNA expression levels in the HCC tissues were 0.84±0.17 and 0.87±0.11, respectively, which were significantly higher than those in the adjacent normal tissues (0.70±0.13 and 0.68±0.13, respectively; P<0.05). Immunohistochemical analysis revealed that MMP2 and HIF-1α protein expression in the HCC tissues was 63.1 and 70.8%, respectively, which was also higher than that in the adjacent normal tissues (34.2 and 36.8%, respectively). There was no significant correlation between the expression of MMP2 or HIF-1α protein and the age or gender of patients with HCC (P>0.05). However, there was significant correlation between MMP2 or HIF-1α protein expression and tumor size, metastasis, presence of a capsule and clinical TNM staging of HCC. Their expression also had a significant effect on patient survival time. In conclusion, MMP2 and HIF-1α are overexpressed in HCC, and the MMP2 signaling pathway may promote the development of HCC together with HIF-1α.

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Section: Discussionmentioning

confidence: 99%

Expression and significance of MMP2 and HIF-1α in hepatocellular carcinoma

et al. 2014

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“…Fujimara et al 10 performed immunohistochemistry for MMP-2, MMP-9, and TIMP-s on surgical specimens from 7 patients with known hemorrhagic cerebral cavernous malformations. 13 All 7 demonstrated strong expression of all 3 markers on the endothelial cells of these lesions, without expression in adjacent normal brain. The conclusions suggested that the expression of these molecules can contribute to the vascular instability within these lesions, conceptually similar to the activity of these molecules within aggressive tumors digesting endothelial basal laminae to maintain their blood-brain barrier permeability.…”

Section: Discussionmentioning

confidence: 89%

“…In 2007, Sakata et al 13 reported on a patient with a cavernous malformation which after resection was found to avidly express MMP-2 and MMP-9. Fujimara et al 10 performed immunohistochemistry for MMP-2, MMP-9, and TIMP-s on surgical specimens from 7 patients with known hemorrhagic cerebral cavernous malformations.…”

Section: Discussionmentioning

confidence: 99%

“…Vascular malformations express both MMP2 and ANXA2. 9,10,12,13 Although some consider vascular malformations to be neoplastic because of their expression of clonal mutations, certainly these vascular entities are distinct from the neoplastic lesions intended to be labeled by tozuleristide both biologically and in terms of their clinical implications. 14 Additionally, although the lesion in case 1 demonstrated significant surrounding edema, Tumor Paint binding was not related to a disruption of the blood-brain barrier, as the molecule is small enough to pass through this barrier without issue, and would wash out by the time of surgery if it did not in fact bind to ligands on the malformation's surface.…”

Section: Discussionmentioning

confidence: 99%

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Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

et al. 2021

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BACKGROUND Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as “Tumor Paint,” is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. OBJECTIVE To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. METHODS Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. RESULTS Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. CONCLUSION This finding deserves further investigation to determine if tozuleristide “Tumor Paint” may have a wider role in the identification of non-neoplastic intracranial pathologies.

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“…Cerebral CMs are associated with other cerebrovascular lesions including vascular malformations, sinus thrombosis, 5) moyamoya disease, 10) and brain tumors. 19) However, association with dural arteriovenous fistula (dAVF) is extremely rare. 5,11) Here we report a case of recurrent dAVF associated with orbital CM, which was not evident at the initial operation for dAVF.…”

Section: Introductionmentioning

confidence: 99%

De Novo Formation of Orbital Cavernous Malformation 9 Years After Surgical Management of Dural Arteriovenous Fistula in the Anterior Middle Fossa -Case Report-

Omodaka

Fujimura

Endo

et al. 2010

Neurol. Med. Chir.(Tokyo)

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Fig. 1 Preoperative images obtained at the initial treatment 9 years previously. A: Left external carotid angiogram, lateral view, showing a left anterior middle fossa dural arteriovenous fistula mainly fed by the left middle meningeal artery and artery of the foramen rotundum, and draining into the superior orbital vein and inferior orbital vein. B: Axial T 2 -weighted magnetic resonance image demonstrating absence of orbital tumor. AbstractA 30-year-old man presented with recurrent dural arteriovenous fistula (dAVF) associated with de novo orbital cavernous malformation (CM), manifesting as progressive left visual disturbance. He had undergone transarterial embolization and subsequent surgical management for a left anterior middle fossa dAVF 9 years previously. External carotid angiography showed recurrence of the dAVF. Magnetic resonance imaging revealed a well delineated intraorbital mass lesion with hypointense signal rim by T 2 -weighted imaging, adjacent to the shunting point of the recurrent dAVF. Transcranial subtotal removal of the intraorbital mass lesion through the orbitopterional approach revealed continuity between the mass lesion and the draining vein of the recurrent dAVF. The histological diagnosis was CM. His symptom was relieved postoperatively, and no regrowth was seen during the follow-up period of one year. The coexistence of recurrent dAVF with newly formed orbital CM is extremely rare, but may indicate the underlying mechanism of the formation of CMs and recurrent dAVF.

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Association of Cavernous Malformation Within Vestibular Schwannoma: Immunohistochemical Analysis of Matrix Metalloproteinase-2 and -9 -Case Report-

Cited by 7 publications

References 17 publications

Expression and significance of MMP2 and HIF-1α in hepatocellular carcinoma

Expression and significance of MMP2 and HIF-1α in hepatocellular carcinoma

Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

De Novo Formation of Orbital Cavernous Malformation 9 Years After Surgical Management of Dural Arteriovenous Fistula in the Anterior Middle Fossa -Case Report-

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