β-Catenin and Novel Associated Proteins in Nasopharyngeal Angiofibromas.
Stephen L Cook, Robin D LeGallo, Stacey E Mills, Edward B Stelow. University of Virginia, Charlottesville
Background: Nasopharyngeal angiofibromas occur at an increased frequency in patients with familial adenomatous polyposis. Furthermore, a majority of sporadic nasopharyngeal angiofibromas has been shown to have nuclear accumulation of β-catenin and have mutations in the β-catenin gene. These results suggest that the Wnt-signaling pathway is important in the pathogenesis of both sporadic and syndrome-associated tumors. End-binding protein 1 (EB1) is an adenomatous polyposis coli (APC)-binding protein which associates with growing ends of microtubules and has been reported to be overexpressed in some carcinomas. Cyclin D1 is a transcriptional target of β-catenin which promotes cell cycle progression. While WT1 functions in transcription regulation, it is now speculated that it also plays a role as a tumor suppressor of the Wnt-signaling pathway. Here, we examine the expression patterns of β-catenin, EB1, cyclin D1, and WT1 in a series of nasopharyngeal angiofibromas.
Design: The study examined 14 nasopharyngeal angiofibromas resected from 14 males ranging in age from 10 to 23 years and found within the surgical pathology files of a single institution. Immunohistochemistry was performed for β-catenin, EB1, cyclin D1, and WT1. Staining pattern and characteristics and the percentage of cells staining were recorded.
Results: All fourteen nasopharyngeal angiofibromas showed prominent nuclear accumulation of β-catenin. In addition, 13 of 13 showed strong, granular cytoplasmic accumulation of EB1. Cyclin D1 showed nuclear staining in a minority of cells (<10% of cells) in 9 of 14 cases. All fourteen tumors showed cytoplasmic staining with WT1. In 7 of 14 (50%) of cases, cytoplasmic WT1 was present in 20 to 50% of cells, while the remaining 7 cases had staining in 70 to 90% of cells.
Conclusions: We confirm the strong and diffuse nuclear accumulation of β-catenin in nasopharyngeal angiofibromas previously noted by others. Cyclin D1 staining supports the functional status of the activated β-catenin. Interestingly, the expression of the novel protein EB1 suggests a role for APC in these tumors. Also, the expression of WT1 in these tumors known to have β-catenin accumulation provides further evidence of its role as a potential tumor suppressor of the Wnt-signaling pathway. Aside from providing information regarding the pathobiology of these tumors, these results also suggest a possible use for these immunostains in the diagnosis of these tumors.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 221, Monday Morning