Introduction: Colorectal cancer expression of Tissue Factor (TF), PAR1 and PAR2 is associated with a poor prognosis. Their stromal, rather than epithelial, expression has prognostic significance in other cancers, this has not been explored in colorectal cancer.
Aim: We aimed to determine the expression patterns of Tissue Factor (TF), PAR1 and PAR2 and thrombin in colorectal cancer and normal tissue.
Materials and methods: Cancer and distant normal tissue were sampled from 37 patients. Expression of TF, Thrombin, PAR1 and PAR2 were determined by immunohistochemistry. Two observers scored expression level (0-3) in individual cells. Percentage of cells having each level of expression was determined and an H-score calculated which are given with 95% CI.
Results: Normal epithelium did not express TF, but it was expressed by cancer epithelium (36.5 (95% CI 17.6 - 55.4) p<0.001). Thrombin expression was increased in cancer vs normal epithelium (126.2 (95% CI 110.6 - 141.7) vs 101.6 (95% CI 92.5-110.8) p=0.01) as was PAR2 (172.4 (95% CI 152.9-191.8) vs 123.4 (95% CI 107.8-139.0) p<0.001). The increase in cancer epithelium PAR1 expression compared to normal (105.4 (95%CI 84.3-126.5) vs 89.0 (95% CI 80.4-97.6)) was not significant. Normal stroma did not express TF or thrombin however both were expressed by cancer stroma (TF 46.3 (95% CI 24.6-68.0) p<0.001, thrombin 11.4 (95% CI 6.2-16.7) p<0.001). PAR1 and PAR2 were both expressed in normal stroma but demonstrated increased expression in cancer stroma (cancer vs normal; PAR 1: 130.7 (95% CI 112.2-149.2) vs 19.5 (95% CI 11.24-27.7) p<0.001; PAR2: 21.5 (95% CI 12.9-30.1) vs 2.21 (95% CI 0.49-3.92) p<0.001).
Conclusions: Upregulated expression of tissue thrombin pathway proteins is seen in colorectal cancer in both epithelial and stromal cells. Procoagulant tumour cells and tumour microenvironment may provide a novel therapeutic target for treatment in colorecal cancer.
© 2016 Elsevier Ltd. All rights reserved.