Acta Neurochir (Wien) (1995) 136:44-50 :Acta . . l'x urochlrurglca 9 Springer-Verlag 1995 Printed in Austria Tenascin Distribution in Human Brain Tumours P. Castellani, A. Dorcaratto, A. Siri, L. Zardi, and G. L. Viale Department of Neurosurgery, University of Genoa Medical School, Genoa and Laboratory of Cell Biology, Istituto Nazionale per la Rieerca sul Cancro, Genoa, Italy Summary Using a monoclonal antibody specific for human tenascin (TN), 180 intracranial growths were immunohistochemically studied. In 69 cases of meningioma, neoplastic cells were negative, with some positivity being observed only in the perivascular and the supporting stroma, especially in anaplastic meningiomas. In 57 cases of glioma different degrees of reactivity occurred in both the cellular conglomerates and the stromal components of the turnouts. A higher variability in reactivity was observed in anaplastic astro- cytomas and glioblastomas. The most constant finding of the study was the staining of the stroma, which was observed in all types of growths, including metastasis, abscess and tuberculoma. The results are consistent with the hypothesis that tenascin is a stromal marker rather than a true marker of malignant tumours. The heterogeneous distribution of TN in anaplastic gliomas may be a factor in the variable response to treatment with radiolab- elled anti-TN monoclonal antibodies. Keywords: Brain tumours; immunohistochemistry; monoclonal antibody (mAb); tenascin (TN). Introduction Tenascin (TN), also known as cytotactin, myoten- dinous antigen, J1220/200, hexabrachion or GMEM (glioma-mesenchymal-extracellular-matrix) glyco- protein, is a polymorphic high molecular mass extra- cellular matrix glycoprotein composed of six similar subunits joined together at their NH2 terminal by di- sulphide bonds. TN shows a restricted distribution in normal adult tissues and plays a role in a variety of processes including cell spreading, adhesion and pro- liferation [7-9, 13, 14, 16, 19]. Neo-expression or dramatically increased expression of TN has been documented during wound healing and in a variety of neoplasms [2, 4, 10, 16, 23-25, 28, 33]. Glioblasto- mas express and accumulate high levels of a glioma- mesenchymal extracellular matrix (GMEM) protein which was later shown to be identical to TN through the use of the monoclonal antibody (mAb) 81C6 [4]. Further reports on human gliomas confirmed this finding [11, 26, 35]. These results have prompted attempts at the intra- venous or intratumoural administration of radiolab- elled anti-TN monoclonal antibodies in order to deliver in vivo cytotoxic radionuclides able to selec- tively bind components of human gliomas [22, 30, 32, 37, 38]. It is known, however, that TN is unevenly expressed in these tumours, its distribution being related to a variety of factors [3, 19, 36]. Owing to the relatively small number of human brain neoplasms thus far investigated and in view of potential thera- peutic implications, an extensive evaluation of TN expression in these tumours is an essential prerequi- site. The purpose of the present work was to study TN distribution in a large series of human brain turnouts and to correlate it with the histological features of the examined oncotypes. Materials and Methods Antibodies This study was carried out using the mAb to TN BC4, obtained and characterized as previously described [ 1, 34]. Tissue Samples Tissues were obtained from the surgical samples of 180 intra- cranial tumours (Table 1). Each sample was divided into 2 por- tions: one was processed for conventional histopathological diag- nosis and the other was immediately snapfrozen in liquid nitrogen. Five micron thick cryostat sections were stained with haematoxy- lin-eosin and additional frozen sections were used for immunohis- tochemical staining after fixation in cold absolute acetone for 10 minutes.