Journal of Neuro-Oncology 45: 127–134, 1999. © 2000 Kluwer Academic Publishers. Printed in the Netherlands. Laboratory Investigation Expression of TGFα in meningiomas ∗ Jaroslava Halper 1 , Chaeyong Jung 1 , Arie Perry 2 , Hagir Suliman 3 , Mary P. Hill 1 and Bernd Scheithauer 2 1 Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, USA; 2 Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, USA; 3 Department of Pulmonary Medicine, Duke University Medical Center, Durham, USA Key words: immunohistochemistry, in situ hybridization, meningioma, transforming growth factor α (TGFα) Comments In this paper, Halper et al. show with careful molecular technique that transforming growth factor α (TGFα) and its receptor are present in meningiomas of varying histotype and grade. There is no real difference among the three grades (benign, atypical, and malignant), but some indication that the meningothelial variant contains less TGFα protein than other types of benign meningioma. The significance of this is uncertain. The simultaneous presence of this ligand and its cell-surface receptor does support the possibility that a stimulatory autocrine loop exists in meningiomas, but proof of that notion will depend on further experiments that examine the effect of TGFα on mitogenesis in cultured meningioma cells, and the effect of agents that block the receptor or its signal transduction pathways. The presence of the receptor is not a novel finding, as it is equivalent to epidermal growth factor (EGF) receptor, which a number of others have shown to be almost universally expressed in meningiomas. In our own investigations of growth factors and other cytokines in meningioma cells, we have found the insulin-like growth factor 1 gives the greatest amount of growth stimulation, and that EGF and platelet-derived growth factor give an intermediate amount of stimulation while fibroblast growth factor is the least effective. We have not thus far tested TGFα in this system. An autocrine loop need not, of course, imply only an overdrive of cell division. As the authors have mentioned, this loop may drive angiogenesis and might also interact with other ligands implicated in meningioma cell proliferation including progesterone, androgens, and prolactin, either to regulate their effect or to be regulated by them. The absence of TGFα in arachnoid granulations, used there to represent ‘tissue of origin,’ only shows that this cytokine is expressed in neoplastic arachnoidal cells, but does not allow the conclusion that it is instrumental in tumorigenesis. Dr. R. Sawaya/Dr. Ian McCutcheon (Houston, TX, USA) Summary The objective of this study was to examine the expression of transforming growth factor α (TGFα), a mitogen for many cell types, and its receptor in basic subtypes of meningiomas as well as in meningiomas of varying grade. Formalin-fixed tissues from 26 meningiomas including 15 benign (5 meningothelial, 5 transitional, and 5 fibrous variants), 6 atypical, and 5 malignant examples were immunohistochemically examined for both TGFα protein and EGF/TGFα receptor protein. In addition, in situ hybridization (ISH) was used to detect TGFα mRNA expression. Immunostaining for TGFα was strongest in fibrous and atypical meningiomas, followed closely by transitional and malignant tumors. Only weak reactivity was observed in the meningothelial variant. In all but 4 tumors (2 fibrous, 2 atypical), ISH showed TGFα mRNA to be present, the signal being stronger in malignant than in conventional or atypical tumors. Lastly, immunostaining for EGF/TGFα receptor was positive in all tumors studied. Strong TGFα protein expression in meningiomas is commonly associated with fibrous morphology. Although the frequent detection of both TGFα protein and its mRNA, as well as of EGF/TGFα receptor within tumors of all type and grades, ∗ Presented in part at The 74th Annual Meeting of the American Association of Neuropathologists, Minneapolis, June 1998.