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MINIMALLY INVASIVE COLORECTAL RESECTION (MICR) IS ASSOCIATED WITH SIGNIFICANTLY ELEVATED LEVELS OF PLASMA MATRIX METALLOPROTEINASE 7 (MMP7) FROM 2ND TO 6TH WEEK AFTER COLORECTAL SURGERY WHICH MAY PROMOTE THE GROWTH OF RESIDUAL METASTASES
H M C Shantha Kumara*1, Erica Pettke1, Geoffrey Bellini1, Abhinit Shah1,2, Xiaohong Yan1, Vesna Cekic1, Nipa D. Gandhi1, Richard L. Whelan1
1Department Of Surgery, Mount Sinai West Hospital, New York 10019,, NY; 2Topiwala National Medical College, Mumbai,Maharashtra-400008, India
Introduction: MMP-7 (matrilysin), a member of Matrix metalloproteinase (MMP) family is expressed in the epithelial cells and in a variety of cancers including colon tumors. MMP7 is capable of digesting many extracellular matrix l matrix (ECM) proteins including collagen IV. MMP7 supports connective tissue remodeling and regulates intestinal innate host defense and innate immunity. The overexpression of MMP7 is associated with inflammation, tumorgenesis, invasion and metastasis. MMP7 regulates neutrophil recruitment during wound induced neoangiogenesis in association with VEGF and TNF-a. It is more proteolytic than MMP2 and MMP3 and capable of activating pro-MMP-1,-2,and-9, and osteopontin. Plasma levels of MMP2, MMP3 and osteopontin are significantly elevated after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) for 3-4 weeks. The impact of MICR for CRC on plasma levels of MMP7 is unknown. This study’s purpose was to evaluate plasma MMP7 levels during first month after MICR for CRC.
Method: CRC patients undergoing MICR who were enrolled in an IRB approved data/plasma bank for whom adequate plasma samples were available included in the study. Clinical, demographic and pathological data were prospectively collected. Blood samples were collected PreOp and at varying postoperative (Postop) time points and were stored at -80C. Only patients for whom PreOp, Postop day (POD) 1, 3 and at least 1late postop plasma sample (POD 7-41) were available were included in this study. The late samples were bundled into 7 day time blocks and considered as single time points. Total MMP7 levels were analyzed in duplicate via ELISA and the results reported as mean and ±SD. The paired t-test was used for analysis (significance, p<0.05).
Results: A total of 87 CRC patients who underwent MICR met the inclusion criteria (43 males: 44 females mean age 65.9 ± 12.8 years; 25% rectal and 75% colon). The mean incision length was 8.6 ± 4.3cm and mean length of stay was 6.7 ± 4.1days. The final cancer staging breakdown was; Stage I, 31%, Stage II, 30%, stage III, 34% and stage IV, 5%. The mean PreOp MMP7 level (ng /ml) was 3.9±1.9 (n=87). Significantly elevated mean plasma levels were noted on POD7-13 (5.5±2.5, n=59, p=< 0.0001), POD14-20 (5.8±2.6, n=23, p=0.0001), POD 21-27 (6.1±3.5, n=18, p=0.001) and on POD 28-41 (6.5±3.1, n=19, p=0.0001) when compared to PreOp levels.
Conclusion: Plasma MMP7 levels remained significantly elevated from preop levels between the 2nd to 6th weeks after MICR for CRC. The increase was 35%-45% over the baseline. The reason for the elevation of MMP7 after the 2nd week is unclear but may be associated with wound healing related inflammation and angiogenesis. Increased plasma MMP7 levels may promote metastases or the growth of residual cancer during the first postop month. Further study is warranted.
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