LOSS OF ALKALINE-PHOSPHATASE ACTIVITY IN MENINGIOMAS - A RAPID HISTOCHEMICAL TECHNIQUE INDICATING PROGRESSION-ASSOCIATED DELETION OF A PUTATIVE TUMOR-SUPPRESSOR GENE ON THE DISTAL PART OF THE SHORT ARM OF CHROMOSOME-1

Apart from defined histomorphologic features, increased Ki-67 indices and various numeric and structural chromosome aberrations, meningiomas of the intermediate (WHO grade II, atypical meningioma) and anaplasti c type (WHO grade III) are cytogenetically distinguished from common-t ype meningiomas (WHO grade I) by frequent loss of the distal part of t he short arm of one chromosome 1 (1p-), which formerly proved to be an independent predictor of shorter recurrence-free intervals. Histochem ically, loss of alkaline phosphatase activity (ALPL, liver/bone/kidney type, EC 3.1.3.1) was another frequent, specific finding in meningiom as with signs of dedifferentiation. In a prospective study including 6 6 meningiomas, all common-type meningiomas except one case (18/19) wer e reactive for ALPL, whereas 75% (30/39) of intermediate type and all anaplastic meningiomas (8/8) showed loss of enzyme activity in large a reas of the tumor. Exclusively, the ALPL negative phenotype was associ ated with Ip loss (15/19). Our data suggest that ALPL, which is coded as a single copy gene on chromosome 1p36.1-p34, is a useful marker enz yme for the loss of a putative regulatory (tumor suppressor) gene on c hromosome Ip, or that ALPL itself represents a new tumor suppressor ge ne homozygously inactivated in meningiomas.