title: Apoptotic and proliferative status in HPV (+) and HPV (-) inverted papilloma patients. Correlation with local recurrence and clinicopathological variables.
abstract: Inverted papilloma (IP) is a rare sinonasal benign lesion characterized by aggressive biological behavior. Our aim was to evaluate the expression of various proliferation and apoptotic markers and the presence of HPV genotypes in paraffin sections gathered from surgically treated IP patients. Immunohistochemistry for PCNA, bax, cytochrome c and caspase-8 and flow cytometry for the detection of apoptosis, necrosis and ki67 expression were performed. The identification of various HPV subtypes was achieved by nested PCR amplification. Nasal polyps (NP) and specimens from normal nasal epithelium (NE) were used as controls. PCNA was more frequently expressed in IP compared to NE (p=0.04) and caspase-8 and bax staining were less frequently observed in IP compared to NP (p=0.004 and p=0.01 respectively) and NE (p=0.003 and p=0.01, respectively). IP and NP presented significantly higher Ki67 flow cytometry values compared to NE (p<0.001 and p=0.02 respectively). Cytochrome c was more frequently expressed in IP specimens with more prominent inflammation (p=0.02). A low HPV DNA detection rate was observed. Neither HPV status nor any of the apoptotic or proliferative markers studied was associated with the patients' clinicopathological characteristics. Increased Ki67 appeared to correlate with disease recurrence (p=0.01). Increased PCNA and Ki67 and decreased bax and caspase-8 expression indicate that cell proliferation is increased while apoptosis is inhibited in IP, explaining its biological behavior.
authors.affiliation: 1st Department of Otolaryngology, Hippocration Hospital of Athens, Athens Medical School, Athens, Greece.
authors.forename: Evagelos
authors.initials: E
authors.lastname: Giotakis
authors.forename: Ilias P
authors.initials: IP
authors.lastname: Gomatos
authors.forename: Leonidas
authors.initials: L
authors.lastname: Alevizos
authors.forename: Leonidas
authors.initials: L
authors.lastname: Manolopoulos
authors.forename: Agapi
authors.initials: A
authors.lastname: Kataki
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kandiloros
authors.forename: Vassilis G
authors.initials: VG
authors.lastname: Gorgoulis
authors.forename: Katerina
authors.initials: K
authors.lastname: Tsimaratou
authors.forename: Manousos M
authors.initials: MM
authors.lastname: Konstantoulakis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Yiotakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local; D009669:Nose Neoplasms / Q000473:pathology* / Q000601:surgery / Q000821:virology; D018308:Papilloma, Inverted / Q000473:pathology* / Q000601:surgery / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D010256:Paranasal Sinuses / Q000473:pathology / Q000821:virology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012189:Retrospective Studies; D014412:Tumor Virus Infections / Q000150:complications / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D018809:Proliferating Cell Nuclear Antigen