Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer

PURPOSE: Membrane-type matrix metalloproteinases are recently described pro teolytic enzymes belonging to the matrix metalloproteinase family. Initial studies have indicated that membrane-type matrix metalloproteinases are inv olved in tumor invasion and metastasis. Membrane-type 1 matrix metalloprote inase is the first membrane-type matrix metalloproteinase to be described. The aim of this study was to investigate the expression of membrane-type 1 matrix metalloproteinase mRNA in colorectal cancer. METHODS: Samples were c ollected from surgical specimens of patients with colorectal adenocarcinoma and were immediately frozen in liquid nitrogen and stored at -80 degrees C until processed. Both normal and cancer tissue was taken from each patient . TNM stage, tumor differentiation, mucin production, and vascular invasion were assessed. Northern blotting was used to quantify membrane-type 1 matr ix metalloproteinase mRNA levels in the samples using a membrane-type 1 mat rix metalloproteinase cDNA clone. X-ray film images were digitized and dens itometry was used to quantify bands. All samples were normalized against 18 S rRNA levels. Results are expressed as the ratio of cancer to normal tissu e levels. Statistical analysis was performed using analysis of variance, wi th P < 0.05 accepted as the level of significance. RESULTS: A total of 32 s amples were prospectively analyzed. The correlation between TNM stage and i ncreased expression of membrane-type 1 matrix metalloproteinase mRNA in can cer tissue over normal tissue is expressed in the mean ratio of cancer to n ormal tissue expression for Stages I through IV, respectively: 1.4 +/- 0.2 (12 patients); 4.1 +/- 2.6 (8 patients); 3.4 +/- 3 (7 patients); and 4.5 +/ - 5 (5 patients). Stage I is significantly different from Stages II and IV (P < 0.05). These preliminary results show an overall increasing trend in m embrane-type 1 matrix metalloproteinase expression with increasing tumor st age. However, there was no correlation between membrane-type 1 matrix metal loproteinase expression and mucin production, degree of tumor differentiati on, or vascular invasion. CONCLUSION: Preliminary results indicate that mem brane-type 1 matrix metalloproteinase levels correlate with increasing tumo r stage.