MMP-9 Expression after Metallic Stent Placement in Patients with Colorectal Cancer: Association with In-Stent Restenosis

Purpose: To verify the expression of matrix metalloproteinase (MMP)-9 in stent-induced hyperplastic tissue from patients with colorectal cancer who received colorectal stents as a bridge to surgery. Materials and Methods: This prospective study was institutional review board-approved, and informed consent was obtained from all patients. Eleven patients (nine men, two women; mean age, 67 years; age range, 53-82 years) with malignant colorectal obstructions who received a colorectal stent between May and December 2010 were included. Tissue specimens were analyzed for MMP-9 and MMP-2 expression. After resection, the tissue was segmented into three parts: tumor tissue, stent-induced tissue hyperplasia, and normal colon tissue. MMP-9 and MMP-2 expression were determined by using zymography, Western blot analysis, and real-time reverse-transcription (qRT) polymerase chain reaction (PCR). Significance of differences between groups was evaluated with Friedman analysis of variance test. Signed-rank test was used to determine differences between malignant tumor tissue and stent-induced hyperplastic tissue groups. Results: Stent placement was technically successful in all 11 patients. Stent-induced hyperplastic tissues were found in all patients. Zymography (P = .003) and Western blot analysis (P = .008) showed that expression of MMP-9 was higher in malignant tumor tissue and stent-induced hyperplastic tissue groups compared with normal colorectal tissue group, demonstrating significant differences between groups but no significant differences between malignant tumor and stent-induced hyperplastic tissues. As for results of qRT PCR analysis, the stent-induced hyperplastic tissue group showed increases in messenger RNA expression level of MMP-9 compared with the malignant tumor tissue group (50.42-fold +/- 66.30 higher). Conclusion: High expression of MMP-9 is closely associated with stent-induced colorectal tissue hyperplasia in patients with colorectal cancer.From the Medical Device Development Center, Osong Medical Innovation Foundation, Cheongwon-gun, Chung-buk, Korea (E.Y.K.); Departments of Radiology and Research Institute of Radiology (H.Y.S.), Surgery (J.C.K., Y.S.Y.), and Gastroenterology (B.D.Y.), University of Ulsan College of Medicine, Asan Medical Center, Asanbyeongwon-gil, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea; Department of Radiology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea (D.H.N.); and Department of Pathology, Asan Medical Center, Seoul, Korea (S.J.S.). From the 2012 RSNA Annual Meeting. Received August 9, 2012; revision requested October 24; revision received July 12, 2013; accepted October 31; final version accepted November 6. Supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare Republic of Korea (A091322, A110476) and grants from the Asan Institute for Life Sciences (2014-069) and the Korea Health 21 R&D Project (A062254), Ministry of Health and Welfare, Republic of Korea. Address correspondence to H-Y. S. (e-mail: hysong@amc.seoul.kr)