The pathogenic molecular mechanisms underlying the insurgence of nasal polyps has not been completely defined. In some patients, these lesions can have a recurrence after surgery removal, and the difference between recurrent and not recurrent patients is still unclear. To molecularly characterize and distinguish between these two classes, a cohort of patients affected by nasal polyposis was analysed. In all patients we analysed the p63 isoform expression using fresh tissues taken after surgery. Moreover, confocal immunofluorescence analysis of fixed sections was performed. The results show high ∆Np63 expression in samples from the nasal polyps of patients compared to the normal epithelia. Analysis of the expression level of the TAp63 isoform shows differential expression between the patients with recurrence compared to those not recurring. The data, considered as the ∆N/TAp63 ratio, really discriminate the two groups. In fact, even though ∆Np63 is expressed in non-recurrent patients, the resulting ratio ∆N/TAp63 is significantly lower in these patients. This clearly indicates that the status of TAp63 expression, represented by the ∆N/TAp63 ratio, could be considered a prognostic marker of low recurrence probability. In these samples we also investigated the expression of OTX2 transcription factor, known to be a selective activator of TAp63, detecting a significant correlation. Database analysis of HNSCC patients showed increased survival for the patients presenting OTX2 amplification and/or overexpression. These results, together with the fact that TAp63 can be selectively upregulated by HDAC inhibitors, open the possibility to consider local treatment of recurrent nasal polyps with these molecules.

Role of the Tap63 isoform in recurrent nasal polyps

Porta G.
Membro del Collaboration Group
;
2019-01-01

Abstract

The pathogenic molecular mechanisms underlying the insurgence of nasal polyps has not been completely defined. In some patients, these lesions can have a recurrence after surgery removal, and the difference between recurrent and not recurrent patients is still unclear. To molecularly characterize and distinguish between these two classes, a cohort of patients affected by nasal polyposis was analysed. In all patients we analysed the p63 isoform expression using fresh tissues taken after surgery. Moreover, confocal immunofluorescence analysis of fixed sections was performed. The results show high ∆Np63 expression in samples from the nasal polyps of patients compared to the normal epithelia. Analysis of the expression level of the TAp63 isoform shows differential expression between the patients with recurrence compared to those not recurring. The data, considered as the ∆N/TAp63 ratio, really discriminate the two groups. In fact, even though ∆Np63 is expressed in non-recurrent patients, the resulting ratio ∆N/TAp63 is significantly lower in these patients. This clearly indicates that the status of TAp63 expression, represented by the ∆N/TAp63 ratio, could be considered a prognostic marker of low recurrence probability. In these samples we also investigated the expression of OTX2 transcription factor, known to be a selective activator of TAp63, detecting a significant correlation. Database analysis of HNSCC patients showed increased survival for the patients presenting OTX2 amplification and/or overexpression. These results, together with the fact that TAp63 can be selectively upregulated by HDAC inhibitors, open the possibility to consider local treatment of recurrent nasal polyps with these molecules.
2019
Chronic rhinosinusitis; Nasal polyps; TAp6
Terrinoni, A.; Palombo, R.; Pitolli, C.; Caporali, S.; Berardinis, R. D. E.; Ciccarone, S.; Lanzillotta, A.; Mauramati, S.; Porta, G.; Minieri, M.; Melino, G.; Bernardini, S.; Bruno, E.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2131608
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