INCREASED ENDOTHELIAL EXPRESSION OF TRANSGLUTAMINASE IN GLIOBLASTOMAS

Transglutaminases are a family of calcium-dependent enzymes that catal yse the formation of covalent crosslinks between proteins. They have s everal diverse functions and are thought to be involved in cell differ entiation, apoptosis and blood coagulation. We have investigated the e xpression of tissue transglutaminase in five fibrillary astrocytomas, five anaplastic astrocytomas and seven glioblastomas by immunohistoche mistry. Strongly labelled tumour cells were seen in most of the fibril lary and anaplastic astrocytomas and all of the glioblastomas. Labelli ng was particularly prominent in the pseudopalisading tumour cells tha t surrounded foci of necrosis and apoptosis in glioblastomas. Most of the immunostained cells did not themselves show morphological features of apoptosis. In addition, apoptotic cells were demonstrated using in situ end-labelling and by in situ hybridization with digoxigenin-labe lled poly(A) oligonucleotide probes. Apoptotic cells demonstrated by b oth of these methods were most numerous in anaplastic astrocytomas and glioblastomas, However, their distribution did not correlate with tha t of the tumour cells showing transglutaminase labelling. Strong trans glutaminase labelling was also observed in the endothelial cells of ve ssels showing microvascular proliferation in all of the glioblastomas studied. In contrast, endothelial transglutaminase labelling was weak or absent in lower grade astrocytic tumours. Enhanced expression of tr ansglutaminase by endothelial cells in glioblastomas may contribute to the high prevalence of vascular thrombosis and necrosis in these tumo urs.