Plasma Levels of Monocyte Chemotactic Protein-1 (MCP-1), a Proangiogenic Protein, Are Persistently Elevated During the First Month After Minimally Invasive Colorectal Cancer Resection.

Hmc Shantha Kumara, PhD, Samer A Naffouje, MD, Sonali A Herath, BS, Elizabeth A Myers, DO, Joon Jang, MD, Linda Njoh, MS, Xiaohong Yan, MDPhD, Daniel Kirchoff, MD, Vesna Cekic, RN, Martin Luchtefeld, MD, Richard L Whelan, MD. (1)(1) Division of Colon and Rectal Surgery, Department of Surgery, St Luke-Roosevelt Hospital Center, Suite 7B, 425 West, 59th Street, New York, NY 10019, USA;(2)(2) Spectrum Health, 25, Michigan Ave SE, Suite 4300, MC 038,Grand Rapids , MI 49503, USA


Introduction: Minimally invasive colorectal resection (MICR) of cancer is associated with persistently elevated plasma levels of VEGF, Angiopoetin 2, sVCAM, and other proangiogenic proteins. Further, plasma from the 2nd and 3rd weeks after MICR has been shown to promote endothelial cell (EC) proliferation, migration and invasion in-vitro which are necessary for neovascularization. This persistent proangiogenic blood composition may stimulate the growth of residual cancer. Monocyte Chemotactic Protein-1 (MCP-1) is a direct mediator of angiogenesis and induces in-vitro EC migration and budding. MCP-1 is produced by EC’s, fibroblasts, and monocytes; MCP-1 expression has also been documented in bladder, prostate and breast malignancies as well as hepatic colorectal metastases. The MCP-1 receptor CCR2 is expressed on the surface of EC’s and is upregulated by inflammatory cytokines; during wound repair it is responsible for endothelial regeneration and vascular remodeling. The impact of colorectal cancer (CRC) resection on blood levels of MCP-1 is unknown. The goal of this study is to evaluate plasma MCP-1 levels during the first month after MICR for CRC.
Method: CRC patients who underwent MICR were eligible. Plasma was obtained from an IRB approved perioperative plasma and data bank. The clinical, demographic and patholigic data was prospectively gathered. Blood samples were obtained PreOp and at varying postop time points and were stored at -80C. Because the timing of late specimens varied and since fewer late specimens were taken, plasma samples for 7-14 day blocks were bundled and considered as single time points. MCP-1 levels were determined in duplicate via ELISA and results reported as mean± SD. The paired t-test was used for analysis (significance p<0.01 after Bonferroni’s correction)
Results: Preop and, at least, 1 late postoperative plasma sample were available for 102 MICR cancer patients (colonic, 71%; rectal 39%; 59 male /43 female, mean age 67.1± 12.3 years). The mean incision length was 7.1± 2.8 cm, mean operative time 266.5± 113 min, and mean length of stay was 5.9±2.3 days. The final cancer staging breakdown was; Stage I, 30%, Stage II, 30%, stage III, 37% and stage IV, 2%. The mean PreOp MCP-1 level was 286.2± 108.3 pg/ml (n=102). When compared to PreOp levels significantly elevated (p<0.001) mean MCP-1 plasma levels (pg/ml) were detected on POD1 (496.6 ± 244.3 ; n=102 ), POD 3 (394.0±224.7 , n=100), POD7-13 (356.6 ± 132.2, n=61), POD14-20 (366.1 ± 99.7,n=27), and POD 21-27 (332.9 ± 78.1,n=28, p=.003).

Conclusion: Plasma MCP-1 levels are significantly elevated over baseline for at least 1 month after MICR. The etiology of this change is unclear. Transient surgery-related increases in inflammatory cytokines may account for MCP-1 elevations during the first week after MICR. Likewise, the persistent late elevations during weeks 2 and 3 may be related to systemic changes associated with wound healing. Elevated MCP-1 levels after MICR and may stimulate the growth of residual tumor or facilitate metastasis formation. Further studies are warranted.

Session Number: Poster – Poster Presentations
Program Number: P110
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