PREDICTION OF COLORECTAL-CANCER RELAPSE AND SURVIVAL VIA TISSUE RNA LEVELS OF MATRIX METALLOPROTEINASE-9

Purpose: In this study, we investigated the association between matrix metalloproteinase (MMP)-9 RNA expression in primary colorectal cancer (CRC) and standard clinicopathologic variables and determined whether levels of MMP-9 RNA predict relapse and survival. Patients and Method s: Tumor and paired normal mucosa specimens from 71 primary CRC patien ts following resections were assessed. RNA levels were determined via Northern blot hybridization and quantitated with laser densitometry. R esults were expressed as tumor/normal mucosa (T/N) fold-increase calcu lated after normalizing for RNA loading using 288 expression. Statisti cal analysis was performed using the SAS statistical package procedure . Kaplan-Meier survival curves were compared with the two-sided log-ra nk test. Results: The mean T/N MMP-9 RNA fold-increase was 9.4 +/- 1.0 (mean +/- SE) (P < .001). Overexpression of MMP-9 RNA correlated sign ificantly with status of synchronous distant metastases (M stage) (P = .004) and Dukes' stage (P = .008). A T/N fold-increase of 5.0 was use d to discriminate between high (> 5.0) and low (less than or equal to 5.0) T/N MMP-9 expression. High T/N MMP-9 RNA expression was associate d with a significantly shorter disease-free (P = .0001) and overall (P = .0002) survival duration, In univariate and multivariate analyses, T/N MMP-9 RNA level was found to be an independent prognostic factor f or disease-free survival. Conclusion: This report provides the first e vidence that increased MMP-9 RNA production in primary human CRC may b e a powerful, independent predictor of recurrence and outcome. (C) 199 6 by American Society of Clinical Oncology.