Co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor in vestibular schwannoma.

Hypothesis: Transforming growth factor-beta1, glial cell line-derived neurotrophic factor, and their receptors are expressed in vestibular schwannoma, and the expression data correlate with the proliferation activity (Ki-67 labeling index) and the clinical growth rate of vestibular schwannoma tissue.

Background: Glial cell line-derived neurotrophic factor is a potent growth factor for the central and peripheral nervous system. Recent results demonstrate that glial cell line-derived neurotrophic factor requires transforming growth factor-beta to exert its trophic effect on neural tissue. A functional role, including that in Schwann cell proliferation, is discussed for both transforming growth factor-beta1 and glial cell line-derived neurotrophic factor.

Methods: Immunohistochemical analysis for transforming growth factor-beta1 and glial cell line-derived neurotrophic factor and their receptors TbetaR II, GFRalpha-1, and Ret was performed on formalin-fixed, paraffin-embedded archival surgical specimens. The Ki-67 labeling index (mean Ki-67 labeling index and highest Ki-67 labeling index for Antoni Type A and Type B regions) and the clinical growth rate of vestibular schwannoma were determined and correlated with the expression patterns of the examined neurotrophic factors and their receptors.

Results: Results demonstrate co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor with higher levels in Antoni Type A than in Antoni Type B regions. Ninety-five percent of vestibular schwannomas exhibited transforming growth factor-beta1 immunoreactivity, and glial cell line-derived neurotrophic factor expression was found in 100% of vestibular schwannoma specimens. Fifty percent of vestibular schwannoma displayed TbetaR II immunostaining, 100% showed positive reactions for GFRalpha-1, and 86% showed positive reactions for Ret. Statistical analysis revealed no significant correlation in neurotrophin expression related to sex, age, tumor size, clinical growth rate, or Ki-67-labeling indices.

Conclusions: Expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor may suggest a biological role for both growth factors in vestibular schwannomas. Trophic transforming growth factor-beta/glial cell line-derived neurotrophic factor synergism seems possible and is underscored by co-expression of both neurotrophic factors and their receptors.