Life Expectancy After Diagnosis of a Vestibular Schwannoma in Patients 70 Years and Older.

Importance: Over the past decades, the number of patients, especially in the older adult patient group, diagnosed with vestibular schwannoma (VS) has increased. Assuming that older adult patients have more comorbidities, a longer recovery period after surgery, a higher rate of surgical complications, and a higher mortality rate after VS surgery, a treatment strategy for this group of patients is warranted, based on clinical evidence on postsurgical survival. Objective: To evaluate the survival after diagnosis of a VS in patients 70 years and older, treated with either observation or surgery, and to compare these findings with the life span of an age-matched background population in Denmark. Design, Setting, and Participants: This was a retrospective cohort study of 624 patients 70 years and older diagnosed with VS in Denmark from 1976 to 2016. Since 1976, all patients with a VS have been registered in a national database, which contains 3637 patients. Of the included patients in this study, 477 were treated conservatively with the "wait-and-scan" strategy, and 147 were treated surgically with removal of the tumor. The survival of the patients was compared with a matched background population in Denmark. Data analysis was performed from January 1976 to January 2017. Exposures: Surgery, radiotherapy, or none. Main Outcomes and Measures: The main outcome was survival among the patients and compared with the matched background population. Results: A total of 624 patients were included (317 female patients [50.8%] and 307 male patients [49.2%]). The mean (SD) survival in the observed patients was 9.2 (4.7) years after diagnosis, whereas for the background population, the expected survival was 11 years from the mean age at diagnosis. For the surgically treated patients, the mean (SD) survival was 11.8 (6.6) years, and expected survival was 11 years for the matched background population. The mean (SD) survival was 10.7 (5.5) years in female patients and 8.9 (5.0) years in male patients. There was no significant difference in survival between treatment modalities, irrespective of tumor size. Conclusions and Relevance: In this cohort study, survival after diagnosis of a VS in patients 70 years and older was similar in the surgical group compared with the age-matched background population. In the wait-and-scan group, the survival after diagnosis was marginally shorter, which may be associated with increased comorbidity.

Natural History of Growing Sporadic Vestibular Schwannomas During Observation: An International Multi-Institutional Study.

OBJECTIVE: Active treatment of small- or medium-sized vestibular schwannoma during wait-and-scan management is currently recommended at most centers globally once growth is detected. The primary aim of the current study was to characterize the natural history of growing sporadic vestibular schwannoma during observation. STUDY DESIGN: Cohort study. SETTING: Four tertiary referral centers across the United States and Denmark. PATIENTS: Patients with two prior MRI scans demonstrating ≥2 mm of linear growth who continued observational management. INTERVENTION: Observation with serial imaging. MAIN OUTCOME MEASURE: Subsequent linear growth-free survival (i.e., an additional ≥2 mm of growth) following initial growth of ≥2 mm from tumor size at diagnosis. RESULTS: Among 3,402 patients undergoing observation, 592 met inclusion criteria. Median age at initial growth was 66 years (IQR 59-73) for intracanalicular tumors (N = 65) and 62 years (IQR 54-70) for tumors with cerebellopontine angle extension (N = 527). The median duration of MRI surveillance following initial detection of tumor growth was 5.2 years (IQR 2.4-6.9) for intracanalicular tumors and 1.0 year (IQR 1.0-3.3) for cerebellopontine angle tumors. For intracanalicular tumors, subsequent growth-free survival rates (95% CI; number still at risk) at 1, 2, 3, 4, and 5 years following the initial MRI that demonstrated growth were 77% (67-88; 49), 53% (42-67; 31), 46% (35-60; 23), 34% (24-49; 17), and 32% (22-47; 13), respectively. For cerebellopontine angle tumors, subsequent growth-free survival rates were 72% (68-76; 450), 47% (42-52; 258), 32% (28-38; 139), 26% (21-31; 82), and 22% (18-28; 57), respectively. For every 1 mm increase in magnitude of growth from diagnosis to tumor size at detection of initial growth, the HRs associated with subsequent growth were 1.64 (95% CI 1.25-2.15; p < 0.001) for intracanalicular tumors and 1.08 (95% CI 1.01-1.15; p = 0.02) for cerebellopontine angle tumors. CONCLUSIONS: Growth detected during observation does not necessarily portend future growth, especially for slowly growing tumors. Because early treatment does not confer improved long-term quality of life outcomes, toleration of some growth during observation is justifiable in appropriately selected cases.

The natural history of vestibular schwannoma growth-prospective 40-year data from an unselected national cohort.

BACKGROUND: Optimal management of vestibular schwannoma (VS) is still debated and thus international consensus has not been achieved. Treatment options are observation, radiotherapy, and surgery. Knowledge on the natural history of tumor growth is essential for choice of treatment modality. The aim is to present intra-/extrameatal tumor growth and management data from a prospective, unselected national cohort of patients diagnosed with VS during the period 1976-2015. METHODS: Since 1976, all data from patients diagnosed with sporadic VS in Denmark have been referred to our national treatment center, where they have been entered prospectively into the national database. Data on tumor localization, growth, and treatment were retrieved. Growth definition: >2 mm by linear measurement, in accordance with the Tokyo 2001 consensus-meeting recommendations. RESULTS: 3637 cases of VS were diagnosed, in which 1304 patients had surgery and 21 received radiotherapy post diagnosis. 2312 patients were observed with mean follow-up of 7.33 years. Of these, 434(19%; 102 intra-and 332 extrameatal tumors) changed to active treatment during the observation period due to tumor growth. 5 years after diagnosis, 21% of the intrameatal tumors exhibited growth during observation, whereas 37% of extrameatal tumors had grown, increasing to 25% intrameatal and 42% extrameatal after 10 years. Following growth, the intrameatal tumors were mostly observed further and the extrameatal mostly underwent surgery. Tumor growth occurred mainly within the first 5 years post diagnosis. CONCLUSION: This natural history study documents the growth occurrence of both intra-and extrameatal VS during the first 12 years after diagnosis and should be used in patient counseling, management, and treatment decision making.

Epidemiology and Diagnostic Characteristics of Vestibular Schwannomas-Does Gender Matter?

INTRODUCTION: A number of epidemiological studies have reported data on, e.g., tumor size and hearing at diagnosis for patients with a vestibular schwannoma (VS), whereas only a few have touched upon the potential significance of sex. The aim of this report is thus to present gender-specific data on incidence and age, tumor localization, tumor size, and hearing loss at diagnosis. MATERIAL AND METHODS: Since 1976, various data for all patients diagnosed with a sporadic VS in Denmark have been entered prospectively into a national database. Data on sex, incidence, age, tumor localization, tumor size, and hearing (discrimination) were extracted for the period 1976 to 2015. RESULTS: Over the 40 years, 3,637 cases were diagnosed, of which 1,804 were women (50%) and 1,833 men (50%). For both sexes, an increasing incidence of tumors with a steadily decreasing size was found. Age was increasing and hearing at diagnosis was increasingly better.Previously, women had more extrameatal and thus larger tumors. During the most recent decade, more tumors were found in men and hearing at diagnosis was better for women, whereas age and tumor size were comparable. CONCLUSION: The data on gender-specific epidemiology and diagnostic characteristics show varying trends over the 40-year-period spanned. For both sexes, an increasing incidence of tumors with a steadily decreasing size was found. Age is increasing and hearing at diagnosis is increasingly better. More extrameatal and thus larger tumors were previously found in women. Contemporarily, more vestibular schwannomas are found in men and diagnostic hearing is better in women.

Epidemiology Of Vestibular Schwannomas - Prospective 40-Year Data From An Unselected National Cohort.

OBJECTIVE: Reports on the epidemiology of vestibular schwannoma (VS) indicate an increase in diagnosed cases, often based on selected materials over a limited period of time. This report presents prospective 40-year epidemiological data from an unselected national cohort of all patients diagnosed with a VS in Denmark since 1976. STUDY-DESIGN: Data on gender, age, tumor localization and size registered during the period 1976-2015 were retrieved. RESULTS: 3637 new cases of VS were diagnosed during the 40-year period. The annual number of diagnosed VS increased from 14 in 1976 to 193 in 2015. Mean extrameatal tumor size decreased from 26mm in 1976 to 13.4mm in 2015. Large and giant tumors were more frequent during the first decades, whereas predominantly smaller tumors were diagnosed during the recent years. Median age at diagnosis increased gradually from 49.2 years in 1976 to 60 years in 2015. CONCLUSION: Over the past 40 years, the incidence rate of vestibular schwannomas has increased steadily from 3 VS/million/year to 34 VS/million/year, primarily due to easier access to improved diagnostics and the finding of more tumors in older people. Concurrently, the diagnostic tumor size has decreased from 26mm to 7mm, and the age at diagnosis has increased from 49 to 60 years.

Residential traffic noise exposure and vestibular schwannoma - a Danish case-control study.

BACKGROUND: Few risk factors for sporadic vestibular schwannoma (VS) are known. Several studies have proposed an increased risk with occupational noise exposure, whereas no studies have investigated residential traffic noise exposure as a risk factor. The present study investigated if residential traffic noise was associated with vestibular schwannoma in a large, population-based Danish case-control study. MATERIAL AND METHODS: We identified 1454 VS cases, age above 30 years at diagnosis, between 1990 and 2007. For each case, we selected two random population controls, matched on sex and year of birth. Road and railway traffic noise at the residence was calculated for all present and historical addresses between 1987 and index date. Associations between traffic noise and risk for VS were estimated using conditional logistic regression, adjusted for education, disposable personal income, cohabitation status, railway noise exposure, municipal population density, and municipal income. RESULTS: A two-year time-weighted mean road traffic noise exposure was associated with an adjusted odds ratio of 0.92 (0.82-1.03) for developing VS, per 10 dB increment. There was no clear trend in categorical analyses. Similarly, linear and categorical analyses of residential railway noise did not suggest an association. We found no interaction with demographics, year of diagnosis, individual and municipal socioeconomic variables, and railway noise exposure. The results did not differ by tumor side, spread or size. CONCLUSIONS: The present study does not suggest an association between residential traffic noise and VS.

Ten-Year Follow-up on Tumor Growth and Hearing in Patients Observed With an Intracanalicular Vestibular Schwannoma.

BACKGROUND: Reports on the natural history of tumor growth and hearing in patients with a vestibular schwannoma (VS) are almost exclusively short-term data. Long-term data are needed for comparison with results of surgery and radiotherapy. OBJECTIVE: To report the long-term occurrence of tumor growth and hearing loss in 156 patients diagnosed with an intracanalicular VS and managed conservatively. METHODS: In this longitudinal cohort study, diagnostic and follow-up magnetic resonance imaging and audiometry were compared. RESULTS: After a follow-up of 9.5 years, tumor growth had occurred in 37% and growth into the cerebellopontine angle had occurred in 23% of patients. Conservative treatment failed in 15%. The pure tone average had increased from 51- to 72-dB hearing level, and the speech discrimination score (SDS) had decreased from 60% to 34%. The number of patients with good hearing (SDS > 70%) was reduced from 52% to 22%, and the number of patients with American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A hearing was reduced from 19% to 3%. Hearing was preserved better in patients with 100% SDS at diagnosis than in patients with even a small loss of SDS. Serviceable hearing was preserved in 34% according to AAO-HNS (class A-B) and in 58% according to the word recognition score (class I-II). Rate of hearing loss was higher in patients with growing tumors. CONCLUSION: Tumor growth occurred in only a minority of patients diagnosed with an intracanalicular VS during 10 years of observation. The risk of hearing loss is small in patients with normal discrimination at diagnosis. Serviceable hearing is preserved spontaneously in 34% according to AAO-HNS and in 58% according to the word recognition score.

Socio-demographic distribution of vestibular schwannomas in Denmark.

CONCLUSION: Vestibular schwannomas (VSs) are diagnosed less frequently in the remote parts of Denmark, whereas the diagnostic age and tumor size is the same across the different socio-demographic areas of Denmark. OBJECTIVE: To determine whether VSs are diagnosed equally often in different socio-demographic areas of Denmark and whether a change has occurred during the period 1976-2012. In addition, differences in diagnostic age and tumor size between areas were explored. METHODS: Since 1976, all patients diagnosed with a VS in Denmark have been registered in a national database, in which information on, for example, the size of the tumor and the age and address of the patient has been registered. Up to 2012, 2739 patients were diagnosed with a VS. Patient distribution according to area of habitat was determined by subgrouping into urban, suburban, rural, and remote municipalities, using the definitions of socio-demographic areas elaborated by Demarks Statistic. RESULTS: The mean national incidence increased almost linearly over the time period from 6.1 per million per year in the first period from 1976 to 1984, to 22.1 per million per year in the last period from 2003 to 2012. There was a lower incidence at the end of the period in the remote areas compared with the other socio-demographic areas (1976-1984, p = 0.05 and 2003-2011, p = 0.001). The mean age at diagnosis increased during the period, from 52.6 years in the first period to 58.6 years in the last period. There was no significant difference in the age distribution between socio- demographic areas. The mean diagnostic tumor size decreased during the period, from 28.6 mm in the first period to about 10 mm in the last period. There was no significant difference in the size of the tumor between socio- demographic areas.

Distinct spontaneous shrinkage of a sporadic vestibular schwannoma.

We present a case with outspoken spontaneous vestibular schwannoma shrinkage and review the related literature. The patient was initially diagnosed with a left-sided, intrameatal vestibular schwannoma, which subsequently grew into the cerebello-pontine angle (CPA), followed by total shrinkage of the CPA component without any intervention over a 12-year observation period. The literature on spontaneous tumor shrinkage was retrieved by searching the subject terms "vestibular schwannoma, conservative management" in PubMed/MEDLINE database, without a time limit. Of the published data, the articles on "shrinkage" or "negative growth" or "regression" or "involution" of the tumor were selected, and the contents on the rate, extent and mechanism of spontaneous tumor shrinkage were extracted and reviewed. The reported rate of spontaneous shrinkage of vestibular schwannoma is 5-10% of patients managed conservatively. Extreme shrinkage of the tumor may occur spontaneously.

Hearing 25 years after surgical treatment of otitis media with effusion in early childhood.

OBJECTIVE: To determine the long-term hearing following surgical treatment of chronic OME in early childhood (myringotomy or ventilation tube) and to determine the impact of the occurrence and the extension of specific eardrum pathology on the hearing level. PATIENTS AND METHODS: In 1977-1978, 224 consecutive children (91 girls and 133 boys) with chronic bilateral OME were enrolled and treated by adenoidectomy, bilateral myringotomy and insertion of a ventilation tube on the right side only. In 2002, a follow-up examination included otomicroscopy and audiometry. Hearing thresholds were compared to an age- and gender-matched normative data set. For the determination of the impact of specific eardrum pathology on the hearing, multiple linear regression modelling was used in adjustment for age and concomitant eardrum pathologies. RESULTS: Long-term hearing after chronic OME and associated treatment is not different from age and gender-matched normal hearing. Treatment modality (myringotomy or ventilation tube) has no impact on the long-term hearing level. The regression analyses showed that the presence of myringosclerosis is associated with an overall hearing loss in myringotomised ears (4-5 dB), but not in tubed ears, for which only high frequencies were affected. Conversely, tensa atrophy is associated with an overall hearing loss in tubed ears (3-4 dB), but not in myringotomised ears, for which only high frequencies were affected. CONCLUSIONS: Hearing 25 years after surgical treatment of chronic OME is not different from age and gender matched normal hearing. In addition, treatment modality (myringotomy or ventilation tube) has no impact on the long-term hearing level. However, atrophy is associated with a hearing loss in tubed ears, whereas myringosclerosis is associated with a hearing loss in myringotomised ears. The hearing loss associated with pathology is of limited magnitude (up to about 5 dB PTA). Even though pathology does occur more frequently and more extensively in tubed ears, the effect on the hearing at the group level is too small to have an impact. It is important to note, that this may be due to a type 2-error (number of patients too small to show an effect).

[Vestibular schwannoma as cause of sudden unilateral deafness and tinnitus]. / Vestibularisschwannom som årsag til pludseligt ensidigt høretab og tinnitus.

Vestibular schwannoma (VS) is a rare disorder. In Denmark, approximately 120 patients are being diagnosed yearly. This is a case report of a 29-year-old female patient with VS, which began with sudden deafness 6-7 years ago. The correct diagnosis was made relatively late.

Fractionated stereotactic radiotherapy of vestibular schwannomas accelerates hearing loss.

OBJECTIVE: To evaluate long-term tumor control and hearing preservation rates in patients with vestibular schwannoma treated with fractionated stereotactic radiotherapy (FSRT), comparing hearing preservation rates to an untreated control group. The relationship between radiation dose to the cochlea and hearing preservation was also investigated. METHODS AND MATERIALS: Forty-two patients receiving FSRT between 1997 and 2008 with a minimum follow-up of 2 years were included. All patients received 54 Gy in 27-30 fractions during 5.5-6.0 weeks. Clinical and audiometry data were collected prospectively. From a "wait-and-scan" group, 409 patients were selected as control subjects, matched by initial audiometric parameters. Radiation dose to the cochlea was measured using the original treatment plan and then related to changes in acoustic parameters. RESULTS: Actuarial 2-, 4-, and 10-year tumor control rates were 100%, 91.5%, and 85.0%, respectively. Twenty-one patients had serviceable hearing before FSRT, 8 of whom (38%) retained serviceable hearing at 2 years after FSRT. No patients retained serviceable hearing after 10 years. At 2 years, hearing preservation rates in the control group were 1.8 times higher compared with the group receiving FSRT (P=.007). Radiation dose to the cochlea was significantly correlated to deterioration of the speech reception threshold (P=.03) but not to discrimination loss. CONCLUSION: FSRT accelerates the naturally occurring hearing loss in patients with vestibular schwannoma. Our findings, using fractionation of radiotherapy, parallel results using single-dose radiation. The radiation dose to the cochlea is correlated to hearing loss measured as the speech reception threshold.

Epidemiology and natural history of vestibular schwannomas.

This article describes various epidemiologic trends for vestibular schwannomas over the last 35 years, including a brief note on terminology. Additionally, it provides information on the natural history of tumor growth and hearing level following the diagnosis of a vestibular schwannoma. A treatment strategy based on the natural history of tumor growth and hearing also is discussed.

Facial nerve function after vestibular schwannoma surgery following failed conservative management.

BACKGROUND: Because only a limited proportion of vestibular schwannomas display growth after diagnosis, an increasing number of patients are managed conservatively. Tumor growth during "wait and scan" may, however, necessitate surgery. In these cases, increased tumor size is likely to increase the risk of impaired facial nerve function after surgery. OBJECTIVE: To compare facial nerve function in patients operated on soon after diagnosis with patients allocated to conservative management and the subgroup of these who later had surgery because of tumor growth. METHODS: A total of 1378 consecutive patients diagnosed with a vestibular schwannoma 20 mm extrameatal or smaller were included; 419 patients were operated on soon after diagnosis, and 959 patients were initially managed conservatively. In the latter group, 161 patients were subsequently operated on owing to tumor growth. RESULTS: All conservatively managed patients had normal facial nerve function at the end of observation. Good facial nerve outcome was found in 87% of patients operated on at diagnosis and in 84% of patients operated on after established tumor growth. For the subgroup of small extrameatal tumors, this difference was significant. When all patients allocated primarily to conservative management were pooled, good facial function was found in 97%, which was significantly better than the result for primary operation (87%). CONCLUSION: Overall, conservative management of small to medium-sized vestibular schwannomas is the best option in terms of preservation of facial nerve function. Tumor growth during observation is found in only a minor proportion of the patients, and in these cases, surgery or irradiation should be performed immediately.

Outcome after translabyrinthine surgery for vestibular schwannomas: report on 1244 patients.

The objective of this article is to study the outcome after translabyrinthine surgery for vestibular schwannomas, with special focus on the facial nerve function. The study design is a case series from a national centralized database and it is set in two University Hospitals in Denmark. Participants were 1244 patients who underwent translabyrinthine surgery during a period of 33 years from 1976 to 2009. Main outcome measures were tumor removal, intraoperative facial nerve preservation, complications, and postoperative facial nerve function. In 84% patients, the tumor was totally resected and in ~85% the nerve was intact during surgery. During 33 years, 12 patients died from complications to surgery and ~14% had cerebrospinal fluid leakage. Before surgery, 74 patients had facial paresis and 46% of these improved after surgery. In patients with normal facial function, overall ~70% had a good outcome (House-Brackmann grade 1 or 2). The chance of a good outcome was related to tumor size with a higher the chance the smaller the tumor, but not to the degree of tumor removal. In ~78% of the patients with facial paresis at discharge the paresis improved over time, in ~42% from a poor to a good function. The translabyrinthine approach is generally efficient in tumor control and with satisfactory facial nerve outcome. With larger tumors the risk of a poor outcome is evident and more data on patients managed with alternative strategies are warranted.

Long-term mobile phone use and the risk of vestibular schwannoma: a Danish nationwide cohort study.

Vestibular schwannomas grow in the region within the brain where most of the energy by radiofrequency electromagnetic fields from using mobile phones is absorbed. The authors used 2 Danish nationwide cohort studies, one a study of all adult Danes subscribing for a mobile phone in 1995 or earlier and one on sociodemographic factors and cancer risk, and followed subjects included in both cohorts for occurrence of vestibular schwannoma up to 2006 inclusively. In this study including 2.9 million subjects, a long-term mobile phone subscription of ≥11 years was not related to an increased vestibular schwannoma risk in men (relative risk estimate = 0.87, 95% confidence interval: 0.52, 1.46), and no vestibular schwannoma cases among long-term subscribers occurred in women versus 1.6 expected. Vestibular schwannomas did not occur more often on the right side of the head, although the majority of Danes reported holding their mobile phone to the right ear. Vestibular schwannomas in long-term male subscribers were not of larger size than expected. Overall, no evidence was found that mobile phone use is related to the risk of vestibular schwannoma. Because of the usually slow growth of vestibular schwannoma and possible diagnostic delay, further surveillance is indicated.

Sociodemographic factors and vestibular schwannoma: a Danish nationwide cohort study.

Vestibular schwannoma (VS) (or acoustic neuroma) accounts for about 5%-6% of all intracranial tumors; little is known about the etiology. We investigated the association between various sociodemographic indicators and VS in a cohort of 3.26 million Danish residents, with 1087 cases identified in 35 308 974 person-years under risk, with data accrued from 1993 to 2006. Complete ascertainment of cases was ensured by using population-based and clinical cancer registries. Information on sociodemographic indicators was obtained on an annually updated individual level from Statistics Denmark. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs). Linear regression models were used to examine the association between sociodemographic indicators and tumor size. We found that IRRs decreased gradually with decreasing level of education, with values of 0.62 (95% CI: 0.49-0.78) for men and 0.62 (95% CI: 0.50-0.77) for women with a basic education compared with a higher education. Similar results were found for disposable income. Marital status was associated with a higher incidence of VS in men but not women; nonmarried men with a basic education had an IRR of 0.34 (95% CI: 0.23-0.50) compared with married men with a higher education. Lower incidence rates were also observed among unemployed or early-retirement pensioners, whereas there were no differences in incidence rates across the broad groups of occupations and across the types of districts. Sociodemographic indicators were not associated with the tumor size. The magnitude of the differences in incidence rates across the groups of different socioeconomic indicators suggests a high potential for earlier diagnosis of VS by improving the awareness of early symptoms.

True incidence of vestibular schwannoma?

BACKGROUND: The incidence of diagnosed sporadic unilateral vestibular schwannomas (VS) has increased, due primarily to more widespread access to magnetic resonance imaging. OBJECTIVE: To present updated epidemiological data on VS incidence, as well as patient age, hearing acuity, tumor size, and localization at diagnosis for the last 4 decades in an unselected population, with emphasis on developments in recent years. METHODS: From 1976 to 2008, 2283 new cases of VS were diagnosed and registered in a national database covering 5.0 to 5.5 million inhabitants. Incidence during the period, patient sex and age, data on hearing (pure tone average and speech discrimination), and tumor size at diagnosis were retrieved from the database. RESULTS: The incidence increased from 3.1 diagnosed VS per million per year in 1976 to a peak of 22.8 VS per million per year in 2004, which was followed by a decrease to 19.4 VS per million per year in 2008. Mean tumor size at diagnosis decreased from 30 mm in 1979 to 10 mm in 2008, whereas hearing acuity at diagnosis has improved over the years. CONCLUSION: After a steady increase over the last 4 decades, the incidence of vestibular schwannomas appears to have peaked and decreased in recent years, stabilizing at about 19 tumors per million per year. Whereas the sex ratio and age at diagnosis have remained grossly unchanged over the years, hearing has improved, and tumor size has decreased considerably.

Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1.

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.