Overexpression of Matrix Metalloproteinase-1 and -9 mRNA Is Associated with Progression of Oral Dysplasia to Cancer

Purpose: Although an important risk factor for oral cancer is the presence of epithelial dysplasia, many lesions will not progress to malignancy. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting various structural components of the extracellular matrix. Because MM...

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Bibliographic Details
Published in:	Clinical cancer research 2004-10, Vol.10 (19), p.6460-6465
Main Authors:	JORDAN, Richard C. K, MACABEO-ONG, Maricris, SHIBOSKI, Caroline H, DEKKER, Nusi, GINZINGER, David G, WONG, David T. W, SCHMIDT, Brian L
Format:	Article
Language:	eng
Subjects:	Antineoplastic agents Biological and medical sciences Carcinoma, Squamous Cell - enzymology Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Disease Progression Gene Expression Regulation, Enzymologic Humans Immunohistochemistry Matrix Metalloproteinase 1 - genetics Matrix Metalloproteinase 1 - metabolism Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Medical sciences Mouth Mucosa - enzymology Mouth Mucosa - metabolism Mouth Mucosa - pathology Mouth Neoplasms - enzymology Mouth Neoplasms - genetics Mouth Neoplasms - pathology Pharmacology. Drug treatments Precancerous Conditions - enzymology Precancerous Conditions - genetics Precancerous Conditions - pathology Reverse Transcriptase Polymerase Chain Reaction - methods RNA, Messenger - genetics RNA, Messenger - metabolism Tumors
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Summary:	Purpose: Although an important risk factor for oral cancer is the presence of epithelial dysplasia, many lesions will not progress to malignancy. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting various structural components of the extracellular matrix. Because MMPs are frequently overexpressed in oral squamous cell carcinoma (SCC), we hypothesized that they are also overexpressed in oral dysplasias; we also hypothesized that those dysplasias that progress to oral cancer express higher levels of MMPs than those lesions that do not progress. Experimental Design: In this retrospective study, we examined changes in MMP-1, -2, and -9 mRNA expression using quantitative TaqMan reverse transcription-polymerase chain reaction in 34 routinely processed oral dysplasias and 15 SCCs obtained from 34 patients. After several years of close follow-up, 19 dysplasias progressed to oral SCC and 15 did not. Results: Overall, MMP-1 mRNA was overexpressed (>2-fold) in 24 of 34 (71%) dysplasias and 13 of 15 (87%) oral SCCs. MMP-2 overexpression was seen in 11 of 34 (32%) dysplasias and 7 of 15 (47%) cancers; for MMP-9, overexpression was identified in 29 of 34 (85%) dysplasias and 15 of 15 (100%) cancers. MMP-1 and -9 levels were significantly higher in the SCCs compared with all oral dysplasias ( P = 0.004 and P = 0.01, respectively). MMP-1 and -9 mRNA levels were significantly higher in the oral dysplasias that progressed to oral cancer compared with those that did not ( P = 0.04 and P = 0.002, respectively). Conclusions: Levels of MMP-1 and -9 mRNA may be markers of malignant transformation of oral dysplasia to oral cancer.
ISSN:	1078-0432 1557-3265