Skull Base 2008; 18(6): 377-384
DOI: 10.1055/s-0028-1096198
ORIGINAL ARTICLE

© Thieme Medical Publishers

Immunohistochemical Investigation of Hormone Receptors and Vascular Endothelial Growth Factor Concentration in Vestibular Schwannoma

Dustin M. Dalgorf1 , Corwyn Rowsell2 , Juan M. Bilbao2 , Joseph M. Chen1
  • 1University of Toronto, Otolaryngology-Head and Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario
  • 2University of Toronto, Department of Neuropathology, Sunnybrook Health Sciences Centre, Toronto, Onatario
Further Information

Publication History

Publication Date:
29 October 2008 (online)

ABSTRACT

Objectives: To determine if a relationship exists between the presence of estrogen receptors (ER), progesterone receptors (PR), or vascular endothelial growth factor (VEGF) and the size, growth rate, and behavior of vestibular schwannoma tumors. Design: Nine tumor samples from young female patients with large vestibular schwannoma tumors were preselected because they were presumed to be faster growing, more aggressive tumors. Immunohistochemical staining was performed using monoclonal mouse antibodies to ER, PR, and VEGF. Results: The mean age of the study sample was 32.3 years, mean tumor size was 3.2 cm, and the average growth rate was 0.4 cm per 2 months. The results of immunohistochemical staining for ER and PR in all nine samples were unequivocally negative. Eight of nine tumor samples stained positive for VEGF, with five demonstrating low intensity and three demonstrating moderate intensity staining. Conclusions: There is histopathological evidence for the expression of VEGF in vestibular schwannomas but not for ER and PR. Further studies are necessary to determine the role of VEGF and other molecular pathways in the growth of vestibular schwannomas and the application of anti-VEGF therapy as a potential treatment option in the future.

REFERENCES

  • 1 van Leeuwen J PPM, Cremers C WRJ, Thewissen N PMW, Harhangi B S, Meijer E. Acoustic neuroma: correlation among tumour size, symptoms, and patient age.  Laryngoscope. 1995;  105 701-707
  • 2 Olivero W C, Lister J R, Elwood P W. The natural history and growth rate of asymptomatic meningiomas: a review of 60 patients.  J Neurosurg. 1995;  83 222-224
  • 3 Wazen J, Silverstein H, Norrell H, Besse B. Preoperative and postoperative growth rates in acoustic neuromas documented with CT scanning.  Otolaryngol Head Neck Surg. 1985;  93 151-155
  • 4 Silverstein H, McDaniel A, Norrell H, Wazen J. Conservative management of acoustic neuroma in the elderly patient.  Laryngoscope. 1985;  95 766-770
  • 5 Gardner G, Moretz W H, Robertson J H, Clark C, Shea Jr J J. Non-surgical management of small and intracanalicular acoustic tumors.  Otolaryngol Head Neck Surg. 1986;  94 328-333
  • 6 Nedzelski J M, Canter R J, Kassel E E, Rowed D W, Tator C H. Is no treatment good treatment in the management of acoustic neuromas in the elderly?.  Laryngoscope. 1986;  96 825-829
  • 7 Nedzelski J M, Schessel D A, Pfleidera A, Kassel E E, Rowed D W. Conservative management of acoustic neuromas.  Otolaryngol Clin North Am. 1992;  25 691-704
  • 8 Lesser T HJ, Janzer R C, Kleihues P, Fisch U. Clinical growth rate of acoustic schwannomas: correlation with the growth fraction as defined by the monoclonal antibody Ki-67.  Skull Base Surg. 1991;  1 11-15
  • 9 Strasnick B, Glasscock M E, Haynes D, McMenomey S O, Minor L B. The natural history of untreated acoustic neuromas.  Laryngoscope. 1994;  104 1115-1119
  • 10 Charabi S, Klinken L, Tos M, Thomsen J. Histopathology and growth pattern of cystic neuromas.  Laryngoscope. 1994;  104 1348-1352
  • 11 Charabi S, Mantoni M, Tos M, Thomsen J. Cystic vestibular schwannomas: neuroimaging and growth rate.  J Laryngol Otol. 1994;  108 375-379
  • 12 McGuire W L. Steroid receptors in breast cancer treatment strategy.  Recent Prog Horm Res. 1980;  36 135-156
  • 13 Valavaara R, Kangas L. The significance of estrogen receptors in tamoxifen and toremifene therapy.  Ann Clin Res. 1988;  20 380-388
  • 14 Rausing A, Ybo W, Stenflo J. Intracranial meningioma: a population study of ten years.  Acta Neurol Scand. 1970;  46 102-110
  • 15 Bickerstaff E R, Small J M, Guest I A. The relapsing course of certain meningiomas in relation to pregnancy and menstruation.  J Neurol Neurosurg Psychiatry. 1958;  21 89-91
  • 16 Kasantikul V, Netsky M G, Glassock III M E, Hays J W. Acoustic neurolemmoma: clinicoanatomical study of 103 patients.  J Neurosurg. 1980;  52 28-35
  • 17 Cayé-Thomasen P, Baandrup L, Jacobsen G, Thomsen J, Stangerup S E. Immunohistochemical demonstration of vascular endothelial growth factor in vestibular schwannomas correlates to tumor growth rate.  Laryngoscope. 2003;  113 2129-2134
  • 18 Cayé-Thomasen P, Werther K, Nalla A et al.. VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumour growth rate.  Otol Neurotol. 2005;  26 98-101
  • 19 Labit-Bouvier C, Crebassa B, Bouvier C, Andrac-Meyer L, Magnan J, Charpin C. Clinicopathologic growth factors in vestibular schwannomas: a morphological and immunohistochemical study of 69 tumours.  Acta Otolaryngol. 2000;  120 950-954
  • 20 Charabi S. Acoustic neuroma/vestibular schwannoma in vivo and in vitro growth models. A clinical and experimental study.  Acta Otolaryngol Suppl. 1997;  530 1-27
  • 21 Dutton J EM, Ramsden R T, Lye R H et al.. Acoustic neuroma (schwannoma) surgery.  J Laryngol Otol. 1991;  105 165-173
  • 22 Markwalder T M, Seiler R W, Zava D T. Antiestrogen therapy of meningioma—a pilot study.  Surg Neurol. 1985;  24 245-249
  • 23 Jaaskelainen J, Laasonen E, Karkkainen J, Haltia M, Troupp H. Hormone treatment of meningioma. Lack of response to medroxyprogesterone acetate (MPA).  Acta Neurochir (Wien). 1986;  80 35-41
  • 24 Beatty C W, Scheithauer B W, Katzmann J A, Roche P C, Kjeldahl K S, Ebersold M J. Acoustic schwannoma and pregnancy: a DNA flow cytometric, steroid hormone receptor, and proliferation marker study.  Laryngoscope. 1995;  105 693-700
  • 25 Chen J M, Houle S, Ang L C et al.. A study of vestibular schwannomas using positron emission tomography and monoclonal antibody Ki-67.  Am J Otol. 1998;  19 840-845
  • 26 Diensthuber M, Brandis A, Lenarz T, Stöver T. Co-expression of transforming growth factor β-1 and glial cell line-derived neurotrophic factor in vestibular schwannoma.  Otol Neurotol. 2004;  25 359-365
  • 27 O'Reilly B F, Kishore A, Crowther J A, Smith C. Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.  Otol Neurotol. 2004;  25 791-796
  • 28 Niemczyk K, Vaneecloo F M, Lecomte M H et al.. Correlation between Ki-67 index and some clinical aspects of acoustic neuromas (vestibular schwannomas).  Otolaryngol Head Neck Surg. 2000;  123 779-783
  • 29 Szeremeta W, Monsell E M, Rock J P, Caccamo D V. Proliferation indices of vestibular schwannomas by Ki-67 and proliferating cell nuclear antigen.  Am J Otol. 1995;  16 616-619
  • 30 Kasantikul V, Brown W J. Estrogen receptors in acoustic neurilemmoma.  Surg Neurol. 1981;  15 105-109
  • 31 Martuza R L, MacLaughlin D T, Ojemann R G. Specific estradiol binding in schwannomas, meningiomas, and neurofibromas.  Neurosurgery. 1981;  9 665-671
  • 32 Wittliff J L. Steroid-hormone receptors in breast cancer.  Cancer. 1984;  53 630-643
  • 33 Monsell E M, Wiet R J. Estrogen and progesterone binding by acoustic neuroma tissue.  Otolaryngol Head Neck Surg. 1990;  103 377-379
  • 34 Whittle I R, Hawkins R A, Miller J D. Sex hormone receptors in intracranial tumours and normal brain.  Eur J Surg Oncol. 1987;  13 303-307
  • 35 Siglock T J, Rosenblatt S S, Finck F, House W F, Hitselberger W E. Sex hormone receptors in acoustic neuromas.  Am J Otol. 1990;  11 237-239
  • 36 Klinken L, Thomsen J, Rasmussen B B, Wiet R, Tos M. Estrogen and progesterone receptors in acoustic neuromas.  Arch Otolaryngol Head Neck Surg. 1990;  116 202-204
  • 37 Curley J WA, Ramsden R T, Howell A, Healy K, Lye R H. Oestrogen and progesterone receptors in acoustic neuroma.  J Laryngol Otol. 1990;  104 865-867
  • 38 Brieger J, Bedavanija A, Jans-Anton L, Maurer J, Mann W. Expression of angiogenic growth factors in acoustic neuroma.  Acta Otolaryngol. 2003;  123 1040-1045
  • 39 Kim K J, Li B, Winer J et al.. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo.  Nature. 1993;  362 841-844
  • 40 Neff B A, Welling D B, Akhamametyeva E, Chang L S. The molecular biology of vestibular schwannomas: dissecting the pathogenic process at the molecular level.  Otol Neurotol. 2006;  27 197-208

Dustin DalgorfM.D. 

Resident Physician, University of Toronto, Otolaryngology-Head and Neck Surgery, Sunnybrook Health Sciences Centre

2075 Bayview Ave, Suite M102, Toronto, Onatrio, Canada M4N 3M5

Email: dustin.dalgorf@utoronto.ca

    >