B7-H1 expression in vestibular schwannomas

David J. Archibald, Brian A. Neff, Stephen G. Voss, Patrick L. Splinter, Colin L W Driscoll, Michael J. Link, Haidong M Dong, Eugene D Kwon

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Hypothesis: B7-H1 is expressed in vestibular schwannomas. Background: Little is known about how benign human vestibular schwannomas interact with antibody-mediated or cell-mediated immunity. We report on the aberrant expression of a novel T-cell coregulatory molecule, B7 homolog 1 (B7-H1), in vestibular schwannomas and discuss the implications of B7-H1 expression and tumor aggressiveness and a potential regulator of B7-H1 expression. Methods: Immunohistochemical staining for B7-H1, CD8+, CD3+, and CD4+ lymphocytes were performed on 48 fresh-frozen vestibular schwannoma tissue specimens. A clinical review of patient presenting symptoms and tumor characteristics was performed. Real-time polymerase chain reaction was used to determine if there was differential expression of B7-H1 messenger RNA and microRNA-513, a known regulator of B7-H1, in several strongly positive and negative B7-H1 vestibular schwannomas. Results: Nine (19%) of 48 tumors were negative, 23 (48%) tumors were 1+ mildly positive (<20% section area), and 16 (33%) stained 2+ strongly positive (≥20% section area) for B7-H1. The average number of CD8+ cells per high-power field was 2.1 for positive-staining tumors and 1.0 for negative tumors (p = 0.16). Failure of tumor control with stereotactic radiation (p = 0.029) was significantly greater in the strongly positive B7-H1 tumors. Real-time polymerase chain reaction did not show significant differential expression of microRNA-513 (p = 0.62) or B7-H1 messenger RNA (p = 0.35) between the tumors showing strong and negative immunohistochemical staining for B7-H1 protein. Conclusion: Vestibular schwannoma tumors express B7-H1, which has been associated with immune tolerance and adverse disease characteristics in several malignancies. Growing tumors that were surgically removed after failed stereotactic radiation therapy were significantly more likely to strongly express B7-H1 protein, which lends some credibility to the hypothesis that immuno-evasion may play some role in their continued growth. Although clinical trends were seen, greater statistical power is required to evaluate whether B7-H1 expression correlates with more aggressive tumor growth or poorer hearing class. B7-H1 seems to be expressed in equal amounts at the RNA level in all vestibular schwannoma tumors that suggests that differential protein expression is occurring at the posttranscriptional level. However, microRNA-513 does not regulate B7-H1 protein expression in these tumors.

Original languageEnglish (US)
Pages (from-to)991-997
Number of pages7
JournalOtology and Neurotology
Volume31
Issue number6
DOIs
StatePublished - Aug 2010

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Acoustic Neuroma
Neoplasms
MicroRNAs
Real-Time Polymerase Chain Reaction
Proteins
B7 Antigens
Staining and Labeling
Negative Staining
Immune Tolerance
Messenger RNA
Growth
Cellular Immunity
Hearing

Keywords

  • Acoustic neuroma
  • Immunology
  • Vestibular schwannoma

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Clinical Neurology
  • Sensory Systems
  • Medicine(all)

Cite this

Archibald, D. J., Neff, B. A., Voss, S. G., Splinter, P. L., Driscoll, C. L. W., Link, M. J., ... Kwon, E. D. (2010). B7-H1 expression in vestibular schwannomas. Otology and Neurotology, 31(6), 991-997. https://doi.org/10.1097/MAO.0b013e3181e40e4f

B7-H1 expression in vestibular schwannomas. / Archibald, David J.; Neff, Brian A.; Voss, Stephen G.; Splinter, Patrick L.; Driscoll, Colin L W; Link, Michael J.; Dong, Haidong M; Kwon, Eugene D.

In: Otology and Neurotology, Vol. 31, No. 6, 08.2010, p. 991-997.

Research output: Contribution to journalArticle

Archibald, DJ, Neff, BA, Voss, SG, Splinter, PL, Driscoll, CLW, Link, MJ, Dong, HM & Kwon, ED 2010, 'B7-H1 expression in vestibular schwannomas', Otology and Neurotology, vol. 31, no. 6, pp. 991-997. https://doi.org/10.1097/MAO.0b013e3181e40e4f
Archibald DJ, Neff BA, Voss SG, Splinter PL, Driscoll CLW, Link MJ et al. B7-H1 expression in vestibular schwannomas. Otology and Neurotology. 2010 Aug;31(6):991-997. https://doi.org/10.1097/MAO.0b013e3181e40e4f
Archibald, David J. ; Neff, Brian A. ; Voss, Stephen G. ; Splinter, Patrick L. ; Driscoll, Colin L W ; Link, Michael J. ; Dong, Haidong M ; Kwon, Eugene D. / B7-H1 expression in vestibular schwannomas. In: Otology and Neurotology. 2010 ; Vol. 31, No. 6. pp. 991-997.
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AU - Archibald, David J.

AU - Neff, Brian A.

AU - Voss, Stephen G.

AU - Splinter, Patrick L.

AU - Driscoll, Colin L W

AU - Link, Michael J.

AU - Dong, Haidong M

AU - Kwon, Eugene D

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N2 - Hypothesis: B7-H1 is expressed in vestibular schwannomas. Background: Little is known about how benign human vestibular schwannomas interact with antibody-mediated or cell-mediated immunity. We report on the aberrant expression of a novel T-cell coregulatory molecule, B7 homolog 1 (B7-H1), in vestibular schwannomas and discuss the implications of B7-H1 expression and tumor aggressiveness and a potential regulator of B7-H1 expression. Methods: Immunohistochemical staining for B7-H1, CD8+, CD3+, and CD4+ lymphocytes were performed on 48 fresh-frozen vestibular schwannoma tissue specimens. A clinical review of patient presenting symptoms and tumor characteristics was performed. Real-time polymerase chain reaction was used to determine if there was differential expression of B7-H1 messenger RNA and microRNA-513, a known regulator of B7-H1, in several strongly positive and negative B7-H1 vestibular schwannomas. Results: Nine (19%) of 48 tumors were negative, 23 (48%) tumors were 1+ mildly positive (<20% section area), and 16 (33%) stained 2+ strongly positive (≥20% section area) for B7-H1. The average number of CD8+ cells per high-power field was 2.1 for positive-staining tumors and 1.0 for negative tumors (p = 0.16). Failure of tumor control with stereotactic radiation (p = 0.029) was significantly greater in the strongly positive B7-H1 tumors. Real-time polymerase chain reaction did not show significant differential expression of microRNA-513 (p = 0.62) or B7-H1 messenger RNA (p = 0.35) between the tumors showing strong and negative immunohistochemical staining for B7-H1 protein. Conclusion: Vestibular schwannoma tumors express B7-H1, which has been associated with immune tolerance and adverse disease characteristics in several malignancies. Growing tumors that were surgically removed after failed stereotactic radiation therapy were significantly more likely to strongly express B7-H1 protein, which lends some credibility to the hypothesis that immuno-evasion may play some role in their continued growth. Although clinical trends were seen, greater statistical power is required to evaluate whether B7-H1 expression correlates with more aggressive tumor growth or poorer hearing class. B7-H1 seems to be expressed in equal amounts at the RNA level in all vestibular schwannoma tumors that suggests that differential protein expression is occurring at the posttranscriptional level. However, microRNA-513 does not regulate B7-H1 protein expression in these tumors.

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KW - Acoustic neuroma

KW - Immunology

KW - Vestibular schwannoma

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