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Keywords:

  • Vestibular schwannoma;
  • cyclin D1 and D3;
  • neurofibromatosis type 2;
  • NF2 gene;
  • cell cycle

Abstract

Objectives: The G1 regulators of the cell cycle, cyclin D1 and D3, have been implicated in the regulation of Schwann cell proliferation and differentiation. The purpose of this study is to evaluate cyclin D1 and D3 protein expression and the corresponding clinical characteristics of vestibular schwannomas.

Study Design and Methods: Tissue sections of 15 sporadic vestibular schwannomas were prepared. Immunohistochemical analysis of the vestibular schwannomas was performed with anticyclin D1 and anticyclin D3 antibodies. The immunoreactivity was evaluated in comparison with adjacent vestibular nerves. Tissue sections of breast carcinoma and prostate carcinoma were used as positive controls for cyclin D1 and D3 staining, respectively. Patient demographics, tumor characteristics, and cyclin D expression were reviewed, and statistical analysis was performed.

Results: While the breast carcinoma control expressed abundant cyclin D1 protein, none of the 15 vestibular schwannomas showed detectable cyclin D1 staining. In contrast, seven of 15 vestibular schwannomas stained positive for the cyclin D3 protein. Cyclin D3 staining was taken up in the nucleus of schwannoma tumor cells in greater proportion than Schwann cells of adjacent vestibular nerve. Although sample size was small, no significant difference in the average age of presentation, tumor size, and male to female ratios for the cyclin D3+ or cyclin D3− groups was found.

Conclusion: The Cyclin D1 protein does not appear to play a prominent role in promoting cell cycle progression in vestibular schwannomas. In contrast, cyclin D3 expression was seen in nearly half of the tumors examined, suggesting that it may have a growth-promoting role in some schwannomas. Further studies are needed to define its cellular mechanism.