Co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor in vestibular schwannoma.
OBJECTIVE
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.
Diensthuber
M
M
Department of Otorhinolaryngology, Hannover Medical University, Hannover, Germany.
Brandis
A
A
Lenarz
T
T
Stöver
T
T
D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D009464:Neuroma, Acoustic / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
C495039:GDNF protein, human; C494987:GFRA1 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D019394:Ki-67 Antigen; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases