This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jordan, R. C. K. Articles by Schmidt, B. L. Search for Related Content PubMed PubMed Citation Articles by Jordan, R. C. K. Articles by Schmidt, B. L.

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

Departments of ¹ Stomatology and ² Pathology and ³ University of California San Francisco Comprehensive Cancer Center, San Francisco California; ⁴ Dental Research Institute, University of California Los Angeles, Los Angeles, California; and ⁵ Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California

ABSTRACT

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.

This article has been cited by other articles:

				R. S. Mitra, M. Goto, J. S. Lee, D. Maldonado, J. M.G. Taylor, Q. Pan, T. E. Carey, C. R. Bradford, M. E. Prince, K. G. Cordell, et al. Rap1GAP Promotes Invasion via Induction of Matrix Metalloproteinase 9 Secretion, Which Is Associated with Poor Survival in Low N-Stage Squamous Cell Carcinoma Cancer Res., May 15, 2008; 68(10): 3959 - 3969. [Abstract] [Full Text] [PDF]

				A. Mehta, C. R. Trotta, and S. W. Peltz Derepression of the Her-2 uORF is mediated by a novel post-transcriptional control mechanism in cancer cells Genes & Dev., April 15, 2006; 20(8): 939 - 953. [Abstract] [Full Text] [PDF]

				K. Shan, Z. Lian-Fu, D. Hui, G. Wei, W. Na, J. Xia, and L. Yan Polymorphisms in the promoter regions of the matrix metalloproteinases-7, -9 and the risk of endometriosis and adenomyosis in China Mol. Hum. Reprod., January 1, 2006; 12(1): 35 - 39. [Abstract] [Full Text] [PDF]