Deletion of chromosome 1p and loss of expression of alkaline phosphatase indicate progression of meningiomas

Meningiomas are cytogenetically characterized by loss of one chromosome 22 as a typical primary aberration and progression-associated secondary chromo some changes, of which monosomy Ip is the most common. The aim of this stud y was to evaluate the significance of monosomy Ip and enzyme activity loss of tissue nonspecific alkaline phosphatase (ALPL), whose gene maps to chrom osome 1p36.1-p34, as parameters for the diagnosis of progression-prone meni ngiomas, We analyzed smear preparations of 56 meningiomas and additional pa raffin sections of 17 of the cases by two-color fluorescence in situ hybrid ization (FISH) using the D1Z1 and D1Z2 probes and by a metaphase cytogeneti c analysis of 30 of these tumors. The results were compared to clinical and morphological parameters and the expression of ALPL, Smear preparations sh owed deletion of 1p36 in 27% of common-type, 70% of atypical (intermediate- type), and 100% of anaplastic meningiomas. Monosomy Ip, as detected by FISH or the karyotype, was strongly associated with complete loss of ALPL activ ity. Intermediate-type and anaplastic meningiomas of younger patients displ ayed an increasing rate of cells with trisomy Iq and relative loss of Ip, T he highly significant correlation of FISH results and ALPL histochemistry w ith clinical parameters gives evidence of their strong prognostic relevance . The complete activity loss of ALPL and the immunologically detected loss of ALPL protein in areas of meningiomas with monosomy Ip indicate a cytogen etically undetectable inactivation of the homologous Alpl allele, The appar ently homozygous loss of expression of ALPL supports the notion that Alpl i s a candidate tumor suppressor gene in meningiomas.