Abstract
Abstract Background. Inflammatory cells and inflammatory mediators play an important role in colon cancer. However, the role of mast cells (MCs) in colon cancer progression remains unclear. Pro-inflammatory cysteinyl leukotrienes (CysLTs) have been associated with colorectal cancer (CRC) development. In particular, previous studies have shown that CRC patients with increased expression of cysteinyl leukotriene receptor 1 (CysLTR1) have poorer prognoses, and Cysltr1−/− mice display fewer intestinal polyps. The aim of the present study was to investigate the clinical and prognostic significance of mast cell density (MCD) in patients with CRC and to determine the significance of CysLTR1 on MCD in a mouse model of colitis-associated colon cancer (CAC). Materials and methods. A tissue microarray (TMA) of primary colon cancers from 72 patients was stained with MC anti-tryptase and anti-chymase antibodies. Mouse colon tissue was stained with MC anti-tryptase antibody. Immunohistochemistry was used to identify MCD in cancerous and normal areas of patient tissues and in polyp/tumour, adjacent and normal areas of mouse tissues. Results. In patient samples, the mean MCD was significantly higher in normal tissue than in cancer tissue (p = 0.0009). Patients with a high MCD in cancer tissue showed better overall survival compared with those with a low MCD (hazard ratio (HR) 0.575; 95% confidence interval (CI), 0.293 - 1.130). The same result was observed in patients aged 55-75 years (HR 0.332; 95% CI 0.121 - 0.911) and among patients without distant metastasis at diagnosis (HR 0.311; 95% CI 0.118 - 0.821). In the CAC mouse model, Cysltr1−/− mice had fewer intestinal polyps and significantly higher MCD in polyp/tumour areas compared with controls. Conclusion. A high MCD in cancer tissue correlates with longer patient survival. In Cysltr1−/− CAC mice, a high polyp/tumour MCD also appears beneficial. Thus, these results indicate that a high MCD is a good prognostic factor. Citation Format: Anita Sjölander. High mast cell density is associated with improved prognosis in colon cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4092.
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