title: Unexpected distribution of CA19.9 and other type 1 chain Lewis antigens in normal and cancer tissues of colon and pancreas: Importance of the detection method and role of glycosyltransferase regulation.
abstract: CA19.9 antigen has been assumed as an abundant product of cancer cells, due to the reactivity found by immunohistochemical staining of cancer tissues with anti-CA19.9 antibody.
  
  
  
  Expression and biosynthesis of type 1 chain Lewis antigens in the colon and the pancreas were studied by immunodetection in tissue sections and lysates, quantification of glycosyltransferase transcripts, bisulfite sequencing, and chromatin immunoprecipitation assays.
  
  
  
  CA19.9 was poorly detectable in normal colon mucosa and almost undetectable in colon cancer, while it was easily detected in the pancreatic ducts, together with Lewis b antigen, under both normal and cancer conditions. B3GALT5 transcripts were down-regulated in colon cancer, while they remained expressed in pancreatic cancer. Even ST3GAL3 transcript appeared well expressed in the pancreas but poorly in the colon, irrespective of normal or cancer conditions. CpG islands flanking B3GALT5 native promoter presented an extremely low degree of methylation in pancreatic cancer with respect to colon cancer. In a DNA region about 1kb away from the B3GALT5 retroviral promoter, a stretch of CG dinucleotides presented a methylation pattern potentially associated with transcription. Such a DNA region and the transcription factor binding site provided overlapping results by chromatin immunoprecipitation assays, corroborating the hypothesis.
  
  
  
  CA19.9 appears as a physiological product whose synthesis strongly depends on the tissue specific and epigenetically-regulated expression of B3GALT5 and ST3GAL3.
  
  
  
  CA19.9 and other Lewis antigens acquire tumor marker properties in the pancreas due to mechanisms giving rise to reabsorption into vessels and elevation in circulating levels.
authors.affiliation: Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, 20142 Milano, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Aronica
authors.affiliation: Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, 20142 Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Avagliano
authors.affiliation: Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, 20142 Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caretti
authors.affiliation: Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, 20142 Milano, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.affiliation: Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, 20142 Milano, Italy; Unit of Human Pathology, Cytogenetics and Molecular Biology, ASST Santi Paolo e Carlo, 20142 Milano, Italy.
authors.forename: Gaetano Pietro
authors.initials: GP
authors.lastname: Bulfamante
authors.affiliation: Department of Medicine Clinical and Experimental (DMCS), University of Insubria Medical School, 21100 Varese, Italy. Electronic address: marco.trinchera@uninsubria.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Trinchera
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D018395:CA-19-9 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005455:Fluorescent Antibody Technique; D005700:Galactosyltransferases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D016695:Glycosyltransferases / Q000378:metabolism*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D000951:Antigens, Neoplasm; D018395:CA-19-9 Antigen; D007983:Lewis Blood Group Antigens; D012333:RNA, Messenger; D004247:DNA; D016695:Glycosyltransferases; C479886:B3GALT5 protein, human; D005700:Galactosyltransferases; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human
keywords: Carbohydrate antigen; Colon cancer; Glycosyltransferase; Pancreatic cancer; Tumor marker, DNA methylation