Pattern of Expression of Cell Cycle–related Proteins in Malignant Transformation of Sinonasal Inverted Papilloma

Abstract

It has been suggested that sinonasal inverted papilloma (IP) can progress to squamous cell carcinoma (SCC); however, mechanisms of malignant transformation are not fully understood. This study investigated alterations in the expression of cell cycle-related proteins in a multistep process of malignant transformation of IPs. The expression of cell cycle-related proteins, including p53, p21, p16, and p63, was evaluated by immunohistochemistry in 21, 56, 7, and 18 cases of nasal polyps, IPs, IPs with dysplasia, and IPs with SCC, respectively. Furthermore, we determined the possible correlation between the expression of these proteins and clinicopathological variables in patients with IPs with SCC. Expression of p53 was found only in 8 of 18 IPs with SCC (44.4%). The frequency of p21 positivity was significantly higher in IPs with dysplasia (71.4%) and IPs with SCC (77.8%) compared with nasal polyps (0%) and IPs (12.5%). A p16 positivity was observed in 82.1% of IPs and 57.1% of IPs with dysplasia, whereas 83.3% of IPs with SCC showed an apparent loss of p16 protein expression. A p63 positivity was found in all specimens, but the percentage of positive cells was significantly increased in IPs with dysplasia and IPs with SCC compared with nasal polyps and IPs. There was no significant correlation between the expression of these proteins and clinicopathological variables, such as tumor stage, histological differentiation, and the proportion of malignant areas in patients with IPs with SCC. Alteration of cell cycle-related proteins may contribute importantly to the malignant transformation from IP to SCC.