Pyruvate kinase isozyme distribution was studied in 75 intracranial tumors. Well-differentiated gliomas, i.e., astrocytomas, oligodendrogliomas, and ependymomas, showed a relatively high residual pyruvate kinase activity in the presence of 4 mm alanine. The reverse was found for poorly differentiated gliomas. Alanine inhibition of pyruvate kinase correlates well with degree of differentiation of these tumors.
There is also a correlation between alanine inhibition of pyruvate kinase and “one year survival” after “total or subtotal” resection of gliomas in adults. In the tumors of 24 patients who died of a recurrence within one year after the operation, a residual pyruvate kinase activity of less than 15% was found. On the contrary, in the tumors of all patients who survived the operation for more than 1 year, a residual activity of 15% and higher was found.
With the exception of a medulloblastoma, all poorly differentiated gliomas were characterized by the presence of type K and the hybrid K3M. In well-differentiated gliomas, besides K4 and K3M, M4 was also present. Alanine inhibition was in agreement with the electrophoretic pattern.
In children (ages 1 and 12 years), gliomas showed no correlation between the distribution of pyruvate kinase isozymes and the histological classification and grading.
Of the nonneuroepithelial tumors studied, relatively high residual activities were found for pyruvate kinase in heman-gioblastoma, chromophobe adenoma, craniopharyngioma, and arteriovenous malformation. Other nonneuroepithelial tumors showed much less residual activity. These include benign tumors, neurilemmoma, cavernoma, and malignant metastatic tumors as well as a fibrosarcoma.
Residual activity of pyruvate kinase in the presence of alanine was decreased in the biopsy of the center of intracerebral neoplasms (n = 64) compared with normal brain tissue. Relatively high residual pyruvate kinase activity was found in the relatively well-differentiated gliomas. When the residual activity is determined not in the center of gliomas but more towards the periphery, much higher residual activity is found. It is proposed that a residual activity of less than 70% is indicative for the presence of tumor in a brain specimen.
Because the alanine inhibition can be performed within 10 min, this test can be used during surgery of intracerebral tumors.
The method cannot be used in children because of the presence of both K4 and M4 in children's brain tissue.