Increased expression of matrix metalloproteinase-2 and 9 and human papilloma virus infection are associated with malignant transformation of sinonasal inverted papilloma.
OBJECTIVE
In this study, we identified matrix metalloproteinase (MMP)-2 and 9 expression in exophytic papilloma (EP), inverted papilloma (IP) with dysplasia, IP with carcinoma, and invasive squamous cell carcinoma (SCC). We also compared the presence of MMP-2 and 9 with human papilloma virus (HPV) infection.


METHODS
The nasal tissue were stained with monoclonal antibodies to MMP-2 and 9. The results were analyzed 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 MMP-2 and 9 were observed in IP with moderate and severe dysplasia, IP with carcinoma, and invasive SCC compared to control nasal mucosa. Among IP, HPV 6/11-positive was present in 41% and HPV 16/18-positive was present in 31%. In HPV 6/11 and 16/18-positive IP, significant increase of MMP-2 and 9 were observed.


CONCLUSIONS
Precancerous lesions of IP exhibited elevated levels of MMP-2 and 9 and these expression may be associated with early events in IP carcinogenesis. HPV infection would be an early event in a multistep process of malignant formation of IP.
Katori
Hideaki
H
Department of Otolaryngology, Yokohama City University Medical Center, Yokohama, Japan. hhkatori@yahoo.co.jp
Nozawa
Akinori
A
Tsukuda
Mamoru
M
D002277:Carcinoma / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D018308:Papilloma, Inverted / Q000378:metabolism* / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000378:metabolism*; D010255:Paranasal Sinus Neoplasms / Q000378:metabolism* / Q000821:virology; D011230:Precancerous Conditions / Q000378:metabolism
D004279:DNA, Viral; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9