Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry

Objective-Activation of polyamine metabolism is closely associated with cel lular proliferation. The purpose was to investigate whether the content of the polyamines putrescine, spermidine, and spermine, and the activity of th e first metabolic key enzyme of polyamine metabolism, ornithine decarboxyla se (ODC), represent biochemical markers of malignancy in brain tumours. Methods-The concentration of putrescine, spermidine, and spermine, and the activity of ODC were biochemically quantified in tissue samples obtained du ring open microsurgery of 670 patients with brain tumours. Biochemical anal ysis and histopathological classification were carried out in serial tumour samples. Results-The activity of ODC was very low in peritumorous non-neoplastic bra in tissue (0.9 (SD 0.6) nmol/g/h). It was significantly higher in gliomas a nd it significantly increased with a higher grade of malignancy (grade 12.7 (2.8) nmol/g/h, grade II 3.1 (4.0) nmol/g/h, grade III 5.7 (5.6) nmol/g/h, grade IV 10.6 (11.7) nmol/g/ h). High enzyme activity was also found in me dulloblastomas (25.5 (15.1) nmol/g/h), malignant lymphomas (52.1 (42.1) nmo l/g/ h), and metastases from carcinoma (14.9 (22.1) nmol/g/h). Lowest value s were measured in epidermoid cysts (0.5 (0.2) nmol/g/h), craniopharyngioma s (1.2 (0.9) nmol/g/h), angioblastomas (1.6 (1.7) nmol/ g/h), and neurinoma s (2.0 (1.8) nmol/g/h). By contrast with ODC activity, polyamine concentrat ions did not correlate with the grade of malignancy. Correlation of regiona l biochemical and histomorphological data in rapidly growing neoplasms show ed high enzyme activity in solid tumour parts and low activity in necrotic areas. Conclusions-Novel data relating ODC activation and polyamine concentrations to neuropathology is presented indicating that high ODC activity represent s a biochemical marker of malignancy in brain tumours. This information is important for clinical and therapeutic investigations.