Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation

Citation
Gp. Nielsen et al., Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation, AM J PATH, 155(6), 1999, pp. 1879-1884
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
0002-9440 → ACNP
Volume
155
Issue
6
Year of publication
1999
Pages
1879 - 1884
Database
ISI
SICI code
0002-9440(199912)155:6<1879:MTONIN>2.0.ZU;2-E
Abstract
Patients with neurofibromatosis 1 (NF1) are predisposed to develop multiple neurofibromas (NFs) and are at risk for transformation of NFs to malignant peripheral nerve sheath tumors (MPNSTs). Little is known, however, about t he biological events involved in the malignant transformation of NFs. We ex amined the CDKN2A/p16 gene and p16 protein in NFs and MPNSTs from patients with NF1. On immunohistochemical analysis, all NFs expressed p16 protein. T he MPNSTs, however, were essentially immunonegative for p16, with striking transitions in cases that contained both benign and malignant elements. Non e of the benign tumors had CDKN2A/p16 deletions, whereas three of six MPNST s appeared to have homozygous CDKN2A/p16 deletions. Methylation analysis an d mutation analysis of CDKN2A/p16 in MPNSTs did not reveal any abnormalitie s. These results show that malignant transformation of NF is associated wit h loss of p16 expression, which is often secondary to homozygous deletion o f the CDKN2A/ p16 gene. The findings suggest that CDKN2A/p16 inactivation o ccurs during the malignant transformation of NFs in NF1 patients and raises the possibility that p16 immunohistochemistry may provide ancillary inform ation in the distinction of NF from MPNST.