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
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.