title: 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- Le(a)/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 alpha(1,2/3/4)FT activities involved in the sequential fucosylation of cores 1 and 2 showed significant increases in tumour tissue. Expressed as microU/mg and control vs. tumour activity (pfrom Wilcoxon's test), the FT activities for Le(a)/Le(b) synthesis were: lacto-N-biose alpha(1,2)/alpha(1,4)FT, 65.4 ± 19.0 vs. 186 ± 35.1 (p< 0.005); lacto-N-fucopentaose 1 alpha(1,4)FT, 64.9 ± 11.9 vs. 125.4 ± 20.7 (p< 0.005); Le(a) alpha(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 alpha(1,2)-/alpha(1,3)FT, 53.4 ± 12.2 vs. 108.1 ± 18.9 (p< 0.001); 2'-Fucosyl-N-acetyllactosamine alpha(1,3)FT, 61.3 ± 10.7 vs. 126.4 ± 22.9 (p< 0.001); 2'-Fucosyllactose alpha(1,3)FT, 38.9 ± 10.9 vs. 143.6 ± 28.9 (p< 0.001); 2'-Methyllactose alpha(1,3)FT, 30.9 ± 4.8 vs. 66.1 ± 8.1 (p< 0.005); and Le(x) alpha(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).
authors.affiliation: Universidad de Vigo.
authors.forename: Almudena
authors.initials: A
authors.lastname: Fernández-Briera
authors.affiliation: Complejo Hospitalario Universitario de Ourense.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cuevas
authors.affiliation: BIOQUÍMICA, GENÉTICA & INMUNOLOGÍA, FACULTAD DE BIOLOGÍA, ESPAÑA.
authors.forename: Emilio
authors.initials: E
authors.lastname: Gil-Martín
mesh_terms: D000368:Aged; D000606:Amino Sugars; D015415:Biomarkers / Q000032:analysis; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007983:Lewis Blood Group Antigens / Q000032:analysis* / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D014312:Trisaccharides
chemical_list: D000606:Amino Sugars; D015415:Biomarkers; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D014312:Trisaccharides; D005643:Fucose; C000458:N-acetyllactosamine; D005647:Fucosyltransferases; C031420:2'-fucosyllactose