Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma

Graffeo, Christopher S.; Perry, Avital; Raghunathan, Aditya; Kroneman, Trynda N.; Jentoft, Mark E.; Driscoll, Colin L. W.; Neff, Brian A.; Carlson, Matthew L.; Jacob, Jeffrey T.; Link, Michael J.; Gompel, Jamie J. Van

doi:10.1055/s-0038-1627474

Cited by 17 publications

(21 citation statements)

References 32 publications

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“…Although the composition varies with each tumor, immune cells can infiltrate the TME and take on several roles that promote and/or resist inflammation and tumor proliferation. 24 Although the mechanisms have not been fully elucidated, several studies have found associations between TAMs, tumor growth, and HL in VS. 5 , 22 , 25 - 28 …”

Section: Discussionmentioning

confidence: 99%

“…In a retrospective investigation of 46 patients with VS with subtotal resections, Graffeo et al 25 found that higher macrophage density (defined as the ratio of CD68 + macrophages to S100 + cells) was significantly associated with tumor progression postoperatively. However, it was unknown whether M1 and/or M2 macrophages were implicated, as CD68 is a nonspecific pan-macrophage marker.…”

Section: Discussionmentioning

confidence: 99%

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Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

et al. 2021

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Objective (1) Characterize the distribution of M1 and M2 macrophages in vestibular schwannomas by hearing status. (2) Develop assays to assess monocyte migration and macrophage polarization in cocultures with vestibular schwannoma cells. Study Design Basic and translational science. Setting Tertiary care center. Methods A retrospective chart review of 30 patients with vestibular schwannoma (VS) was performed. Patients were stratified into serviceable and unserviceable hearing groups. Immunohistochemistry for CD80+ M1 and CD163+ M2 macrophages was conducted. Primary VS cultures (n = 4) were developed and cocultured with monocytes. Immunohistochemistry for macrophage markers was performed to assess monocyte migration and macrophage polarization. Results Although tumors associated with unserviceable hearing had higher levels of CD80 and CD163 than those with serviceable hearing, the relationship was only significant with CD163 ( P = .0161). However, CD163 level did not remain a significant predictor variable associated with unserviceable hearing on multivariate analysis when adjusted for other variables. In vitro assays show that VS cells induced monocyte migration and polarization toward CD80+ M1 or CD163+ M2 macrophage phenotypes, with qualitative differences in CD163+ macrophage morphologies between serviceable and unserviceable hearing groups. Conclusion Vestibular schwannomas express varying degrees of CD80+ M1 and CD163+ M2 macrophages. We present evidence that higher expression of CD163+ may contribute to poorer hearing outcomes in patients with VS. We also describe in vitro assays in a proof-of-concept investigation that VS cells can initiate monocyte migration and macrophage polarization. Future investigations are warranted to explore the relationships between tumor, macrophages, secreted cytokines, and hearing outcomes in patients with VS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

et al. 2021

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“…We were able to gather individual patient-level data for 349 patients from 6 studies (Table 2). 2,12,13,17,18,20 The range of Ki-67 index values for patients with recurrence was 1.4-4.8%, whereas the range for patients without recurrence was 0.6-1.9%.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…31 Graffeo et al and Kontorinos et al showed that there are increased immune cells in VSs that have more rapid growth. 12,29 Graffeo et al demonstrated that tumors with higher S100 and CD68 macrophages tended to have a more aggressive growth pattern after subtotal resection. 12 These results have…”

Section: Ki-67 Index and The Role For Prognostication In Vs Managementmentioning

confidence: 99%

Predictive Value of Ki-67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis

Vakharia

Hasegawa²,

Graffeo

et al. 2022

J Neurol Surg B Skull Base

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Background: Ki-67 is often used as a proliferation index to evaluate how aggressive a tumor is and its likelihood of recurrence. Vestibular schwannomas (VS) are a unique benign pathology that lends itself well to evaluation with Ki-67 as a potential marker for disease recurrence or progression following surgical resection. Methods: All English language studies of VSs and Ki-67 indices were screened. Studies were considered eligible for inclusion if they reported series of VSs undergoing primary resection without prior irradiation, with outcomes including both recurrence/progression and Ki-67 for individual patients. For published studies reporting pooled Ki-67 index data without detailed by-patient values, we contacted the authors to request data sharing for the current meta-analysis. Studies reporting a relationship between Ki-67 index and clinical outcomes in VS for which detailed patients’ outcomes or Ki-67 indices could not be obtained were incorporated into the descriptive analysis, but excluded from the formal (i.e., quantitative) meta-analysis. Results: A systematic review identified 104 candidate citations, of which 12 met inclusion criteria. Six of these studies had accessible patient-specific data. Individual patient data were collected from these studies for calculation of discrete study effect sizes, pooling via random-effects modeling with restricted maximum likelihood, and meta-analysis. The standardized mean difference in Ki-67 indices between those with and without recurrence was calculated as 0.79% (95%CI=0.28-1.30; P=0.0026). Conclusion: Ki-67 index may be higher in VSs that demonstrate recurrence/progression following surgical resection. This may represent a promising means of evaluating tumor recurrence and potential need for early adjuvant therapy for VSs.

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“…1,7,[11][12][13] The principal factor determining VII nerve damage at the time of surgical resection is the size of the VS itself, with tumor vascularity, the tumour micro-environment and tumour consistency also playing a part. [14][15][16][17][18][19][20] Patients with VSs associated with neurofibromatosis type-2 also seem to be at risk of adverse VII nerve outcomes following surgical resection. 21 With smaller tumors (<20mm), rates of VII nerve palsy following VS resection are less than 10%, 16,19 but for larger tumors (>30mm) VII nerve function is affected in more than half of patients undergoing surgical resection.…”

Section: Facial (Vii) Nerve Weaknessmentioning

confidence: 99%

Neuro-Ophthalmic Complications of Vestibular Schwannoma Resection: Current Perspectives

Chiu¹,

Hickman²,

Pepper³

et al. 2021

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Vestibular schwannomas (VSs), also called acoustic neuromas, are benign intracranial neoplasms of the vestibulocochlear (VIII) cranial nerve. Management options include “wait-and-scan,” stereotactic radiosurgery and surgical resection. Due to the proximity of the VIII nerve to the facial (VII) nerve in the cerebello-pontine angle, the VII nerve is particularly vulnerable to the effects of surgical resection. This can result in poor eye closure, lagophthalmos and resultant corneal exposure post VS resection. Additionally, compression from the tumor or resection can cause trigeminal (V) nerve damage and a desensate cornea. The combination of an exposed and desensate cornea puts the eye at risk of serious ocular complications including persistent epithelial defects, corneal ulceration, corneal vascularization, corneal melting and potential perforation. The abducens (VI) nerve can be affected by a large intracranial VS causing raised intracranial pressure (a false localizing sign) or as a result of damage to the VI nerve at the time of resection. Other types of neurogenic strabismus are rare and typically transient. Contralaterally beating nystagmus as a consequence of vestibular dysfunction is common post-operatively. This generally settles to pre-operative levels as central compensation occurs. Ipsilaterally beating nystagmus post-operatively should prompt investigation for post-operative cerebrovascular complications. Papilledema (and subsequent optic atrophy) can occur as a result of a large VS causing raised intracranial pressure. Where papilledema follows surgical resection of a VS, it can indicate that cerebral venous sinus thrombosis has occurred. Poor visual function following VS resection can result as a combination of all these potential complications and is more likely with larger tumors.

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Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma

Cited by 17 publications

References 32 publications

Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Predictive Value of Ki-67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis

Neuro-Ophthalmic Complications of Vestibular Schwannoma Resection: Current Perspectives

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