基质金属蛋白酶-1和-9信使核糖核酸的过表达与口腔发育异常向癌症的进展相关。

Overexpression of matrix metalloproteinase-1 and -9 mRNA is associated with progression of oral dysplasia to cancer.

作者信息

Jordan Richard C K, Macabeo-Ong Maricris, Shiboski Caroline H, Dekker Nusi, Ginzinger David G, Wong David T W, Schmidt Brian L

机构信息

Department of Stomatology, University of California San Francisco Comprehensive Cancer Center, San Francisco, California 94143-0424, USA.

出版信息

Clin Cancer Res. 2004 Oct 1;10(19):6460-5. doi: 10.1158/1078-0432.CCR-04-0656.

DOI:10.1158/1078-0432.CCR-04-0656

PMID:15475433

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.

摘要

目的

尽管上皮发育异常是口腔癌的一个重要危险因素，但许多病变不会发展为恶性肿瘤。基质金属蛋白酶（MMPs）是一类依赖锌的蛋白酶，能够消化细胞外基质的各种结构成分。由于MMPs在口腔鳞状细胞癌（SCC）中经常过度表达，我们推测它们在口腔发育异常中也会过度表达；我们还推测，那些发展为口腔癌的发育异常比未发展的病变表达更高水平的MMPs。

实验设计

在这项回顾性研究中，我们使用定量TaqMan逆转录-聚合酶链反应检测了34例常规处理的口腔发育异常和15例从34例患者中获取的SCC中MMP-1、-2和-9 mRNA表达的变化。经过数年的密切随访，19例发育异常进展为口腔SCC，15例未进展。

结果

总体而言，34例发育异常中的24例（71%）和15例口腔SCC中的13例（87%）MMP-1 mRNA过度表达（>2倍）。34例发育异常中的11例（32%）和15例癌症中的7例（47%）出现MMP-2过度表达；对于MMP-9，34例发育异常中的29例（85%）和15例癌症中的15例（100%）检测到过度表达。与所有口腔发育异常相比，SCC中的MMP-1和-9水平显著更高（分别为P = 0.004和P = 0.01）。与未进展的口腔发育异常相比，进展为口腔癌的发育异常中MMP-1和-9 mRNA水平显著更高（分别为P = 0.04和P = 0.002）。