Urinary matrix metalloproteinases as a potential screening test for gynecologic malignancies

Objective. This was a pilot study to determine the feasibility of using urinary matrix metalloproteinases (MMPs) as a screening test for gynecologic malignancies. Methods. Urine samples from ovarian (n = 29), cervical (n = 31), endometrial (n = 31), and vulvar (n = 5) cancer patients and 19 controls were collected. Substrate gel electrophoresis (zymography) was used to determine the presence of MMP-2 (72 kDa), MNIP-9 (92 kDa) and two high-molecular-weight forms (130 and 220 kDa) of MMPs. The sensitivity, specificity, and positive and negative predictive values of the test for each tumor type were determined. Results. No association was noted between malignancy and presence of urinary MMPs in ovarian, cervical, endometrial, or vulvar cancer patients. Sensitivity, specificity, negative and positive predictive values, and likelihood ratios were determined. Sensitivities ranged from 28.1 to 51.0% for individual MMPs, peaking at 69.8% when the presence of any of the four proteinases was considered a positive test. Specificities ranged from 42.1 to 68.4%. Conclusion. Our study suggests that the presence of MMPs in the urine of patients with a gynecologic malignancy is not an adequate screening test for disease. There was also little evidence of an association between urinary MMPs and stage or extent of disease. However, the limited number of patients in the various stages of each disease site, specifically advanced stage disease, make it difficult to state this definitively. (C) 2003 Elsevier Science (USA). All rights reserved.