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Open Access 01-06-2012 | Original Article

Intratumoral hemorrhage, vessel density, and the inflammatory reaction contribute to volume increase of sporadic vestibular schwannomas

Authors: Maurits de Vries, Pancras C. W. Hogendoorn, Inge Briaire-de Bruyn, Martijn J. A. Malessy, Andel G. L. van der Mey

Published in: Virchows Archiv | Issue 6/2012

Abstract

Vestibular schwannomas show a large variation in growth rate, making prediction and anticipation of tumor growth difficult. More accurate prediction of clinical behavior requires better understanding of tumor biological factors influencing tumor progression. Biological processes like intratumoral hemorrhage, cell proliferation, microvessel density, and inflammation were analyzed in order to determine their role in vestibular schwannoma development. Tumor specimens of 67 patients surgically treated for a histologically proven unilateral vestibular schwannoma were studied. Preoperative magnetic resonance imaging (MRI) scans were used to determine tumor size and to classify tumors as homogeneous, inhomogeneous, and cystic. Immunohistochemical studies evaluated cell proliferation (histone H3 and Ki-67), microvessel density (CD31), and inflammation (CD45 and CD68). Intratumoral hemorrhage was assessed by hemosiderin deposition. The expression patterns of these markers were compared with tumor size, tumor growth index, MRI appearance, patients’ age, and duration of symptoms. No relation between cell proliferation and clinical signs of tumor volume increase or MRI appearance was found. Intratumoral hemosiderin, microvessel density, and inflammation were significantly positively correlated with tumor size and the tumor growth index. Cystic and inhomogeneous tumors showed significantly more hemosiderin deposition than homogeneous tumors. The microvessel density was significantly higher in tumors with a high number of CD68-positive cells. The volume increase of vestibular schwannomas is not based on cell proliferation alone. Factors like intratumoral bleeding, (neo)vascularization, and intensity of the inflammatory reaction also influence tumor volume.

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Szeremeta W, Monsell EM, Rock JP, Caccamo DV (1995) Proliferation indices of vestibular schwannomas by Ki-67 and proliferating cell nuclear antigen. Am J Otol 16(5):616–619PubMed

Niemczyk K, Vaneecloo FM, Lecomte MH, Lejeune JP, Lemaitre L, Skarzynski H et al (2000) Correlation between Ki-67 index and some clinical aspects of acoustic neuromas (vestibular schwannomas). Otolaryngol Head Neck Surg 123(6):779–783PubMedCrossRef

Davidson EJ, Morris LS, Scott IS, Rushbrook SM, Bird K, Laskey RA et al (2003) Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia. Br J Cancer 88(2):257–262PubMedCrossRef

Brenner RM, Slayden OD, Rodgers WH, Critchley HO, Carroll R, Nie XJ et al (2003) Immunocytochemical assessment of mitotic activity with an antibody to phosphorylated histone H3 in the macaque and human endometrium. Hum Reprod 18(6):1185–1193PubMedCrossRef

Takahashi H, Murai Y, Tsuneyama K, Nomoto K, Okada E, Fujita H et al (2006) Overexpression of phosphorylated histone H3 is an indicator of poor prognosis in gastric adenocarcinoma patients. Appl Immunohistochem Mol Morphol 14(3):296–302PubMedCrossRef

(1995) Committee on Hearing and Equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular schwannoma). American Academy of Otolaryngology-Head and Neck Surgery Foundation, INC. Otolaryngol Head Neck Surg 113(3):179–180.

Bovee JV, van den Broek LJ, de Boer WI, Hogendoorn PC (1998) Expression of growth factors and their receptors in adamantinoma of long bones and the implication for its histogenesis. J Pathol 184(1):24–30PubMedCrossRef

Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M et al (2002) Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 38(12):1564–1579PubMedCrossRef

Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL (1995) Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 177(3):275–283PubMedCrossRef

10.

de Andrea CE, Wiweger MI, Bovee JV, Romeo S, Hogendoorn PC (2011) Peripheral chondrosarcoma progression is associated with increased type X collagen and vascularisation. Virchows Arch 460(1):95–102PubMedCrossRef

11.

Koutsimpelas D, Stripf T, Heinrich UR, Mann WJ, Brieger J (2007) Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics. Otol Neurotol 28(8):1094–1099PubMedCrossRef

12.

Bedavanija A, Brieger J, Lehr HA, Maurer J, Mann WJ (2003) Association of proliferative activity and size in acoustic neuroma: implications for timing of surgery. J Neurosurg 98(4):807–811PubMedCrossRef

13.

Gomez-Brouchet A, Delisle MB, Cognard C, Bonafe A, Charlet JP, Deguine O et al (2001) Vestibular schwannomas: correlations between magnetic resonance imaging and histopathologic appearance. Otol Neurotol 22(1):79–86PubMedCrossRef

14.

Jeng CM, Huang JS, Lee WY, Wang YC, Kung CH, Lau MK (1995) Magnetic resonance imaging of acoustic schwannomas. J Formos Med Assoc 194(8):487–493

15.

Fundova P, Charabi S, Tos M, Thomsen J (2000) Cystic vestibular schwannoma: surgical outcome. J Laryngol Otol 114(12):935–939PubMedCrossRef

16.

Jones SE, Baguley DM, Moffat DA (2007) Are facial nerve outcomes worse following surgery for cystic vestibular schwannoma? Skull Base 17(5):281–284PubMedCrossRef

17.

Sinha S, Sharma BS (2008) Cystic acoustic neuromas: surgical outcome in a series of 58 patients. J Clin Neurosci 15(5):511–515PubMedCrossRef

18.

Charabi S, Mantoni M, Tos M, Thomsen J (1994) Cystic vestibular schwannomas: neuroimaging and growth rate. J Laryngol Otol 108(5):375–379PubMedCrossRef

19.

Park CK, Kim DC, Park SH, Kim JE, Paek SH, Kim DG et al (2006) Microhemorrhage, a possible mechanism for cyst formation in vestibular schwannomas. J Neurosurg 105(4):576–580PubMedCrossRef

20.

Stadlbauer A, Buchfelder M, Nimsky C, Saeger W, Salomonowitz E, Pinker K et al (2008) Proton magnetic resonance spectroscopy in pituitary macroadenomas: preliminary results. J Neurosurg 109(2):306–312PubMedCrossRef

21.

Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186PubMedCrossRef

22.

Charabi S, Simonsen K, Charabi B, Jacobsen GK, Moos T, Rygaard J et al (1996) Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice. Acta Otolaryngol 116(1):59–63PubMedCrossRef

23.

Charabi S (1997) Acoustic neuroma/vestibular schwannoma in vivo and in vitro growth models. A clinical and experimental study. Acta Otolaryngol Suppl 530:1–27PubMed

24.

van Rijswijk CS, Kunz P, Hogendoorn PC, Taminiau AH, Doornbos J, Bloem JL (2002) Diffusion-weighted MRI in the characterization of soft-tissue tumors. J Magn Reson Imaging 15(3):302–307PubMedCrossRef

25.

Bonneville F, Savatovsky J, Chiras J (2007) Imaging of cerebellopontine angle lesions: an update. Part 2: intra-axial lesions, skull base lesions that may invade the CPA region, and non-enhancing extra-axial lesions. Eur Radiol 17(11):2908–2920PubMedCrossRef

26.

Pedrosa I, Alsop DC, Rofsky NM (2009) Magnetic resonance imaging as a biomarker in renal cell carcinoma. Cancer 115(10 Suppl):2334–2345PubMedCrossRef

27.

Brieger J, Bedavanija A, Lehr HA, Maurer J, Mann WJ (2003) Expression of angiogenic growth factors in acoustic neurinoma. Acta Otolaryngol 123(9):1040–1045PubMedCrossRef

28.

Labit-Bouvier C, Crebassa B, Bouvier C, Andrac-Meyer L, Magnan J, Charpin C (2000) Clinicopathologic growth factors in vestibular schwannomas: a morphological and immunohistochemical study of 69 tumours. Acta Otolaryngol 120(8):950–954PubMedCrossRef

29.

Buddingh EP, Kuijjer ML, Duim RA, Burger H, Agelopoulos K, Myklebost O et al (2011) Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents. Clin Cancer Res 17(8):2110–2119PubMedCrossRef

30.

Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30(7):1073–1081PubMedCrossRef

31.

Hsu HP, Shan YS, Lai MD, Lin PW (2010) Osteopontin-positive infiltrating tumor-associated macrophages in bulky ampullary cancer predict survival. Cancer Biol Ther 10(2):144–154PubMedCrossRef

32.

Lin EY, Nguyen AV, Russell RG, Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193(6):727–740PubMedCrossRef

33.

Mantovani A, Romero P, Palucka AK, Marincola FM (2008) Tumour immunity: effector response to tumour and role of the microenvironment. Lancet 371(9614):771–783PubMedCrossRef

34.

Ojalvo LS, Whittaker CA, Condeelis JS, Pollard JW (2010) Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. J Immunol 184(2):702–712PubMedCrossRef

35.

Qian B, Deng Y, Im JH, Muschel RJ, Zou Y, Li J et al (2009) A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One 4(8):e6562PubMedCrossRef

36.

Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86(5):1065–1073PubMedCrossRef

37.

Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F et al (2005) Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res 65(7):2964–2971PubMedCrossRef

38.

Mukhtar RA, Nseyo O, Campbell MJ, Esserman LJ (2011) Tumor-associated macrophages in breast cancer as potential biomarkers for new treatments and diagnostics. Expert Rev Mol Diagn 11(1):91–100PubMedCrossRef

Title: Intratumoral hemorrhage, vessel density, and the inflammatory reaction contribute to volume increase of sporadic vestibular schwannomas
Authors: Maurits de Vries
Pancras C. W. Hogendoorn
Inge Briaire-de Bruyn
Martijn J. A. Malessy
Andel G. L. van der Mey
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 6/2012
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-012-1236-9

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Intratumoral hemorrhage, vessel density, and the inflammatory reaction contribute to volume increase of sporadic vestibular schwannomas

Abstract

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