Cyclin D1 and D3 Expression in Vestibular Schwannomas

Objectives: The G 1 regulators of the cell cycle, cyclin D 1 and D 3 , have been implicated in the regulation of Schwann cell proliferation and differentiation. The purpose of this study is to evaluate cyclin D 1 and D 3 protein expression and the corresponding clinical characteristics of vestibular schwannomas. Study Design and Methods: Tissue sections of 15 sporadic vestibular schwannomas were prepared. Immunohisto-chemical analysis of the vestibular schwannomas was performed with anticyclin D 1 and anticyclin D 3 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 D 1 and D 3 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 D 1 protein, none of the 15 vestibular schwannomas showed detectable cyclin D 1 staining. In contrast, seven of 15 vestibular schwannomas stained positive for the cyclin D 3 protein. Cyclin D 3 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 D 3 + or cyclin D 3 - groups was found. Conclusion: The Cyclin D 1 protein does not appear to play a prominent role in promoting cell cycle progression in vestibular schwannomas. In contrast, cyclin D 3 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.