Carbohydrate antigen 19.9 (CA19.9) is used as a tumor marker for clinical and research purposes assuming that it is abundantly produced by gastrointestinal cancer cells due to a cancer-associated aberrant glycosylation favoring its synthesis. Recent data has instead suggested a different picture, where immunodetection on tissue sections matches biochemical and molecular data. In addition to CA19.9, structurally related carbohydrate antigens Lewis a and Lewis b are, in fact, undetectable in colon cancer, due to the down-regulation of a galactosyltransferase necessary for their synthesis. In the pancreas, no differential expression of CA19.9 or cognate glycosyltransferases occurs in cancer. Ductal cells only express such Lewis antigens in a pattern affected by the relative levels of each glycosyltransferase, which are genetically and epigenetically determined. The elevation of circulating antigens seems to depend on the obstruction of neoplastic ducts and loss of polarity occurring in malignant ductal cells. Circulating Lewis a and Lewis b are indeed promising candidates for monitoring pancreatic cancer patients that are negative for CA19.9, but not for improving the low diagnostic performance of such an antigen. Insufficient biological data are available for gastric and bile duct cancer. Studying each patient in a personalized manner determining all Lewis antigens in the surgical specimens and in the blood, together with the status of the tissue-specific glycosylation machinery, promises fruitful advances in translational research and clinical practice.

Complementary use of carbohydrate antigens lewis a, lewis b, and sialyl-lewis a (Ca19.9 epitope) in gastrointestinal cancers : biological rationale towards a personalized clinical application / R. Indellicato, A. Zulueta, A. Caretti, M. Trinchera. - In: CANCERS. - ISSN 2072-6694. - 12:6(2020 Jun 09), pp. 1509.1-1509.15. [10.3390/cancers12061509]

Complementary use of carbohydrate antigens lewis a, lewis b, and sialyl-lewis a (Ca19.9 epitope) in gastrointestinal cancers : biological rationale towards a personalized clinical application

R. Indellicato
Primo
;
A. Zulueta
Secondo
;
A. Caretti;
2020-06-09

Abstract

Carbohydrate antigen 19.9 (CA19.9) is used as a tumor marker for clinical and research purposes assuming that it is abundantly produced by gastrointestinal cancer cells due to a cancer-associated aberrant glycosylation favoring its synthesis. Recent data has instead suggested a different picture, where immunodetection on tissue sections matches biochemical and molecular data. In addition to CA19.9, structurally related carbohydrate antigens Lewis a and Lewis b are, in fact, undetectable in colon cancer, due to the down-regulation of a galactosyltransferase necessary for their synthesis. In the pancreas, no differential expression of CA19.9 or cognate glycosyltransferases occurs in cancer. Ductal cells only express such Lewis antigens in a pattern affected by the relative levels of each glycosyltransferase, which are genetically and epigenetically determined. The elevation of circulating antigens seems to depend on the obstruction of neoplastic ducts and loss of polarity occurring in malignant ductal cells. Circulating Lewis a and Lewis b are indeed promising candidates for monitoring pancreatic cancer patients that are negative for CA19.9, but not for improving the low diagnostic performance of such an antigen. Insufficient biological data are available for gastric and bile duct cancer. Studying each patient in a personalized manner determining all Lewis antigens in the surgical specimens and in the blood, together with the status of the tissue-specific glycosylation machinery, promises fruitful advances in translational research and clinical practice.
Colorectal cancer; Glycosyltransferase; Pancreatic ductal adenocarcinoma; Selectin ligand; Tumor marker
Settore BIO/10 - Biochimica
Article (author)
File in questo prodotto:
File Dimensione Formato  
cancers-12-01509-v2.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.29 MB
Formato Adobe PDF
1.29 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/752338
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact