Dysregulated survivin expression in nasal polyps of individuals with aspirin exacerbated respiratory disease.

BACKGROUND: A derailed balance of cell proliferation and apoptosis is presumed to result in cell hyperplasia as a typical feature of nasal polyps. Survivin, a protein of the inhibitors of the apoptosis family is proposed to promote polyp formation. However, studies concerning survivin expression in chronic rhinosinusitis (CRS) with nasal polyps are rare and the specificity of the survivin expression in nasal polyps from individuals with aspirin-exacerbated respiratory disease (AERD) has not been investigated. METHODS: Immunohistochemical survivin expression analysis was performed. Samples were taken from the ethmoid sinus of individuals with CRS with nasal polyps with and without AERD during sinus surgery and control specimens of the inferior turbinate from individuals without CRS. Cell cultures were stimulated with recombinant vascular endothelial growth factor (VEGF(165)) and the resulting survivin expression was analyzed by Western blot. RESULTS: The survivin expression of 61 specimens was analyzed by quantitative immunohistochemistry and a potential VEGF-dependant stimulation of survivin in cell cultures was investigated. The survivin expression in nasal polyps from individuals with AERD was increased compared with the controls (median, 1194 versus 927 arbitrary units [A.U.]; p = 0.054). Western blot analysis revealed in vitro a VEGF-dependant regulation of survivin in nasal polyps from individuals without AERD, but not in those with AERD (p = 0.05). CONCLUSION: Enhanced survivin expression might result in decreased apoptosis and cellular hyperplasia as a part of the largely unknown pathophysiology of nasal polyp formation. Furthermore, we hypothesize a pathological, VEGF-independent constitutive survivin expression in nasal polyps of individuals with AERD.

Vascular endothelial growth factor expression in nasal polyps of aspirin-intolerant patients.

OBJECTIVE: To study differences between aspirin-tolerant patients and aspirin-intolerant patients concerning vascular endothelial growth factor (VEGF) expression. Recent publications strongly suggest the involvement of VEGF and its receptors in the pathophysiologic process of nasal polyps. DESIGN: We subjected 43 polyp specimens to semiquantitative immunohistochemical analysis. We quantified VEGF and its receptors (Flk, Flt, and neuropilin) in all samples. To gain insight into potential VEGF-mediated cellular responses, we determined proliferative (Ki67) and apoptotic (caspase 3) indices. PATIENTS: Polyp samples were obtained from 22 aspirin-intolerant patients and from 21 aspirin-tolerant patients, and control specimens were obtained from 24 subjects with healthy nasal respiratory mucosa. SETTING: Laboratory; Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. MAIN OUTCOME MEASURES: Expression levels of VEGF, VEGF receptors. and proliferative and apoptotic indices. RESULTS: We found higher expressed levels of VEGF and neuropilin and stronger proliferation in nasal polyps from aspirin-tolerant and aspirin-intolerant patients compared with controls. In polyps from aspirin-intolerant patients, VEGF was expressed at considerably higher levels compared with those from aspirin-tolerant subjects. Apoptotic activity remained unchanged in all 3 groups. CONCLUSIONS: Nasal polyps from aspirin-tolerant and aspirin-intolerant patients are characterized by strong proliferation and high levels of VEGF and neuropilin expression. Nasal polyps from aspirin-intolerant patients show distinctly increased VEGF levels. The relevance of these findings for future therapeutic approaches is yet to be determined.