Markers of malignant transformation of sinonasal inverted papilloma.
OBJECTIVE
To measure HPV status, epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) expression and Ki-67 index in exophytic papilloma (EP), inverted papilloma (IP) with dysplasia, IP with carcinoma and invasive squamous cell carcinoma (SCC).


METHODS
Forty-four patients with sinonasal papilloma and invasive SCC were selected. The nasal tissues were stained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The results were analysed using quantitative immunohistochemical analysis. In situ hybridization studies for HPV DNA for 6/11, 16/18 and 31/33 were also performed on the tissue.


RESULTS
Significant increase of EGFR and TGF-alpha was observed in IP with severe dysplasia, IP with carcinoma and invasive SCC compared to IP with mild dysplasia and control nasal mucosa. And a serial upreguration in terms of Ki-67 index in IP with dysplasia was observed. Among IP, HPV 6/11-positive was present in 42% tumour and HPV 16/18-positive was present in 31% of tumours. Among HPV 6/11 and 16/18-positive IP, significant increase of EGFR and Ki-67 index were observed.


CONCLUSIONS
Pre-cancerous lesions of IP exhibited elevated levels of EGFR and TGF-alpha and these expression may be associated with early events in IP carcinogenesis. HPV infection may be an early event in a multistep process of malignant formation of IP.
Katori
H
H
Department of Otolaryngology, Yokohama City University Medical Center, 4-57 Urafune-chou, Minami-ku, Yokohama 232-0024, Japan.
Nozawa
A
A
Tsukuda
M
M
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000473:pathology; D009361:Neoplasm Invasiveness; D009669:Nose Neoplasms / Q000473:pathology*; D010212:Papilloma / Q000473:pathology; D018308:Papilloma, Inverted / Q000473:pathology*; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification; D010255:Paranasal Sinus Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors