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.


OBJECTIVE
We investigated SIPs relationships between HPV infection and aberrant expression of cell cycle proteins.


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).
Department of Medical-Diagnostic Sciences and Special Therapies, Section of Otolaryngology, University of Padua, Via Gabelli 61, Padua, Italy. giuseppe.altavilla@unipd.it
Giuseppe
G
Altavilla
Alberto
A
Staffieri
Graziella
G
Busatto
Alessandra
A
Canesso
Luciano
L
Giacomelli
Gino
G
Marioni
D019938:Cyclin D1 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015344:DNA Probes, HPV; D005786:Gene Expression Regulation / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D019394:Ki-67 Antigen / Q000235:genetics*; D009669:Nose Neoplasms / Q000235:genetics* / Q000473:pathology; D018308:Papilloma, Inverted / Q000235:genetics* / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology; D010255:Paranasal Sinus Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D055273:Salivary Proline-Rich Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C530104:CCND1 protein, human; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015344:DNA Probes, HPV; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C524744:PRB1 protein, human; D055273:Salivary Proline-Rich Proteins; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27