Frequent beta-catenin mutations in juvenile nasopharyngeal angiofibromas.
Am J Pathol, 158 (3):
1073-1078 (March 2001)Abstract
Juvenile nasopharyngeal angiofibromas (JNAs) are locally aggressive
vascular tumors occurring predominantly in adolescent males. The
pathogenesis of JNAs is unknown. Recently, JNAs have been reported
to occur at increased frequency among patients with familial adenomatous
polyposis, suggesting that alterations of the adenomatous polyposis
coli (APC)/beta-catenin pathway might also be involved in the pathogenesis
of sporadic JNAs. We analyzed somatic beta-catenin and APC gene mutations
in 16 sporadic JNAs from nonfamilial adenomatous polyposis patients
using immunohistochemistry for beta-catenin, and direct DNA sequencing
for exon 3 of the beta-catenin gene and the mutation cluster region
of the APC gene. Nuclear accumulation of beta-catenin was diffusely
present in the stromal cells but not in the endothelial cells of
all 16 JNAs. Activating beta-catenin gene mutations were present
in 75% (12 of 16) of JNAs. Six JNA patients also had recurrent tumors
after surgery, and in all cases the beta-catenin gene status of the
recurrent JNA was identical to the initial tumor. No mutations in
the mutation cluster region of the APC gene were detected in the
four JNAs without beta-catenin mutations. The high frequency of beta-catenin
mutations in sporadic JNAs and the presence of identical beta-catenin
gene mutations in recurrent tumors indicates that activating beta-catenin
gene mutations are important in the pathogenesis of JNAs. The immunohistochemical
localization of beta-catenin only to the nuclei of stromal cells
further suggests that the stromal cells, rather than endothelial
cells, are the neoplastic cells of JNAs.