Expression of p53, p16INK4A, pRb, p21WAF1/CIP1, p27KIP1, cyclin D1, Ki-67 and HPV DNA in sinonasal endophytic Schneiderian (inverted) papilloma

CONCLUSIONS: Human papilloma virus (HPV) was associated with sinonasal inverted papilloma (SIP) in 14/20 (70%) patients with a prevalence of HPV 6/11; alterations of the cell cycle proteins were statistically significant. OBJECTIVES: We investigated SIPs relationships between HPV infection and aberrant expression of cell cycle proteins. MATERIALS AND METHODS: Twenty SIPs were evaluated for p53, p16(INK4a), pRb, p21(WAF1), p27(Kip1), cyclin D1 and Ki-67 expression by immunohistochemistry. HPV was investigated by polymerase chain reaction (PCR). RESULTS: HPV DNA was detected in 14/20 patients with inverted papillomas (IPs) (70%). The majority of tumours showed strong p16, p21, p27, pRb and cyclin D1 staining and little or no p53 expression. Tumours harbouring dysplasia were significantly more likely to be p53-positive and exhibit up-regulated p21 and p27, and showed altered intensity and distribution of reactive cells into and through the epithelium. Dysplastic epithelium was strongly reactive for p16 and the MIB 1 labelling index was almost 20%. These findings were associated with expression of p53 in the same zones. Comparing the p53 reactivity with the presence of HPV DNA, SIPs were stratified as follows: HPV + p53-, 12 (63.15%); HPV + p53+, 2 (10.52%); HPV - p53+, 3 (15.78%) and HPV - p53-, 2 (10.52%). Statistical analysis showed that HPV presence correlated with p53-positive immunostaining (p=0.045).