Role of matrix metalloproteinases in colorectal carcinogenesis

Objective To measure coexpression of matrix metalloproteinase (MMP)-2, MMP-7, and MMP -9 genes by real-time quantitative reverse transcriptase-polymerase chain r eaction (qRT-PCR) in benign and malignant phases of colorectal carcinogenes is. Summary Background Data Matrix metalloproteinases degrade and remodel the extracellular matrix and have been implicated in facilitating carcinoma cells to invade and metastas ize. MMP-2, MMP-7, and MMP-9 have been shown to be overexpressed in various carcinomas; however, simultaneous examination of these enzymes in human no rmal mucosa, adenoma, and carcinoma has not been performed to date. Methods Between January 1, 1998, and June 15, 2000, 40 patients underwent colectomy and harvest and snap-freezing of normal mucosa, adenoma, and carcinoma. Fi ve patients had adenoma and carcinoma in the same specimen; 35 had either a denoma (n = 6) or carcinoma (n = 29). Taqman qRT-PCR methodology was used t o measure MMP gene copy number and normalized to p-actin RNA expression. Results The mean age was 62 +/- 4 years, with 22 men and 18 women. One fifth of the adenomas exhibited severe dysplasia. MMP-7 gene expression was significant ly increased in adenomas (43 times normal mucosa) but did not increase furt her in carcinomas (50 times normal mucosa). MMP-2 and MMP-9 were not differ ent in adenomas (1.8 and 1.4 times normal mucosa, respectively) but were el evated in carcinomas (2.2 and 1.8 times normal mucosa, respectively). There was no correlation between size or dysplasia in adenomas or AJCC stage in carcinomas and MMP gene expression. Conclusions Overexpression of MMP-7 is an early event in the adenoma-to-carcinoma pathw ay, and expression does not appear to increase further in carcinomas. MMP-2 and MMP-9 appear to be primarily overexpressed in carcinomas. This may be one mechanism by which adenoma cells gain the ability to invade and carcino ma cells to metastasize.