Deletion of Chromosome 1p and Loss of Expression of Alkaline Phosphatase Indicate Progression of Meningiomas

• Published in: Clinical cancer research Vol. 5; no. 11; pp. 3569 - 3577
• Main Authors: MIILLER, P, HENN, W, NIEDERMAYER, I, KETTER, R, FEIDEN, W, STEUDEL, W.-I, ZANG, K. D, STEILEN-GIMBEL, H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-11-1999
• Subjects: Alkaline Phosphatase - genetics; Biological and medical sciences; Biopsy; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 1; Disease Progression; Female; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Medical sciences; Meningeal Neoplasms - enzymology; Meningeal Neoplasms - genetics; Meningeal Neoplasms - pathology; Meningioma - enzymology; Meningioma - genetics; Meningioma - pathology; Monosomy; Neurology; Trisomy; Tumors of the nervous system. Phacomatoses; Human; Alkaline phosphatase; Nervous system diseases; Prognosis; Enzyme; Phosphoric monoester hydrolases; Chromosome A1; Esterases; Malignant meningioma; Malignant tumor; Gene expression; Carcinogenesis; Fluorescence in situ hybridization; Tumor progression; Cytogenetics; Deletion; Hydrolases; Diagnosis; Tumor cell; Tumor suppressor gene
• ISSN: 1078-0432; 1557-3265

Meningiomas are cytogenetically characterized by loss of one chromosome 22 as a typical primary aberration and progression-associated
secondary chromosome changes, of which monosomy 1p is the most common. The aim of this study was to evaluate the significance
of monosomy 1p and enzyme activity loss of tissue nonspecific alkaline phosphatase (ALPL), whose gene maps to chromosome 1p36.1-p34,
as parameters for the diagnosis of progression-prone meningiomas. We analyzed smear preparations of 56 meningiomas and additional
paraffin sections of 17 of the cases by two-color fluorescence in situ hybridization (FISH) using the D1Z1 and D1Z2 probes and by a metaphase cytogenetic analysis of 30 of these tumors. The results
were compared to clinical and morphological parameters and the expression of ALPL. Smear preparations showed deletion of 1p36
in 27% of common-type, 70% of atypical (intermediate-type), and 100% of anaplastic meningiomas. Monosomy 1p, as detected by
FISH or the karyotype, was strongly associated with complete loss of ALPL activity. Intermediate-type and anaplastic meningiomas
of younger patients displayed an increasing rate of cells with trisomy 1q and relative loss of 1p. The highly significant
correlation of FISH results and ALPL histochemistry with 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
1p indicate a cytogenetically undetectable inactivation of the homologous Alpl allele. The apparently homozygous loss of expression of ALPL supports the notion that Alpl is a candidate tumor suppressor gene in meningiomas.