Revista Espanola de Enfermedades Digestivas (Oct 2015)
Screening of enzymatic synthesis and expression of Lewis determinants in human colorectal carcinoma
Abstract
Background: Although colorectal carcinogenesis has been intensively studied, the published investigations do not provide a consistent description of how different carbohydrate determinants of colorectal epithelium are modified in colorectal cancer (CRC). Objective: This study is an attempt to characterize the terminal fucosylation steps responsible for the synthesis of mono-(Leª/Le x) and difucosylated (Le b/Le y) Lewis antigens in healthy and tumour CRC tissue. Methods: An immunohistochemical study of Lewis antigens' expression was undertaken, along with screening of the fucosyltransferase (FT) activities involved in their synthesis, on healthy and tumour samples from 18 patients undergoing CRC. Results: Analysis of α(1,2/3/4)FT activities involved in the sequential fucosylation of cores 1 and 2 showed significant increases in tumour tissue. Expressed as μU/mg and control vs. tumour activity (p from Wilcoxon's test), the FT activities for Leª/Le b synthesis were: lacto-N-biose α(1,2)/α(1,4)FT, 65.4 ± 19.0 vs. 186 ± 35.1 (p < 0.005); lacto-N-fucopentaose 1 α(1,4)FT, 64.9 ± 11.9 vs. 125.4 ± 20.7 (p < 0.005); Leª α(1,2)FT, 56.2 ± 7.2 vs. 130.5 ± 15.6 (p < 0.001). Similarly, for Le x/Le y synthesis were: N-acetyllactosamine α(1,2)-/α(1,3)FT, 53.4 ± 12.2 vs. 108.1 ± 18.9 (p < 0.001); 2'-Fucosyl-N-acetyllactosamine α(1,3)FT, 61.3 ± 10.7 vs. 126.4 ± 22.9 (p < 0.001); 2'-Fucosyllactose α(1,3)FT, 38.9 ± 10.9 vs. 143.6 ± 28.9 (p < 0.001); 2'-Methyllactose α(1,3)FT, 30.9 ± 4.8 vs. 66.1 ± 8.1 (p < 0.005); and Le x α(1,2)FT, 54.3 ± 11.9 vs. 88.2 ± 14.4 (p < 0.001). Immunohistochemical Le y expression was increased (p < 0.01 according to Wilcoxon's test) in tumour tissue, with 84.6% of specimens being positive: 7.7% weak, 15.4% moderate and 61.5% high intensity. Conclusions: Results suggest the activation of the biosynthesis pathways of mono-and difucosylated Lewis histo-blood antigens in tumour tissue from CRC patients, leading to the overexpression of Le y, probably at the expense of Le x.
