TY - JOUR
T1 - Frequent β-catenin mutations in juvenile nasopharyngeal angiofibromas
AU - Abraham, Susan C.
AU - Montgomery, Elizabeth A.
AU - Giardiello, Francis M.
AU - Wu, Tsung Teh
PY - 2001
Y1 - 2001
N2 - 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)/β-catenin pathway might also be involved in the pathogenesis of sporadic JNAs. We analyzed somatic β-catenin and APC gene mutations in 16 sporadic JNAs from nonfamilial adenomatous polyposis patients using immunohistochemistry for β-catenin, and direct DNA sequencing for exon 3 of the β-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of β-catenin was diffusely present in the stromal cells but not in the endothelial cells of all 16 JNAs. Activating β-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 β-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 β-catenin mutations. The high frequency of β-catenin mutations in sporadic JNAs and the presence of identical β-catenin gene mutations in recurrent tumors indicates that activating β-catenin gene mutations are important in the pathogenesis of JNAs. The immunohistochemical localization of β-catenin only to the nuclei of stromal cells further suggests that the stromal cells, rather than endothelial cells, are the neoplastic cells of JNAs.
AB - 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)/β-catenin pathway might also be involved in the pathogenesis of sporadic JNAs. We analyzed somatic β-catenin and APC gene mutations in 16 sporadic JNAs from nonfamilial adenomatous polyposis patients using immunohistochemistry for β-catenin, and direct DNA sequencing for exon 3 of the β-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of β-catenin was diffusely present in the stromal cells but not in the endothelial cells of all 16 JNAs. Activating β-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 β-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 β-catenin mutations. The high frequency of β-catenin mutations in sporadic JNAs and the presence of identical β-catenin gene mutations in recurrent tumors indicates that activating β-catenin gene mutations are important in the pathogenesis of JNAs. The immunohistochemical localization of β-catenin only to the nuclei of stromal cells further suggests that the stromal cells, rather than endothelial cells, are the neoplastic cells of JNAs.
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U2 - 10.1016/S0002-9440(10)64054-0
DO - 10.1016/S0002-9440(10)64054-0
M3 - Article
C2 - 11238055
AN - SCOPUS:0035106770
SN - 0002-9440
VL - 158
SP - 1073
EP - 1078
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -