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.
Highlights
The outcome of gastrointestinal cancers, in particular pancreatic ductal adenocarcinoma (PDAC), is unfavorable when recognized at an advanced stage
We suggest that the future use of Lewis antigens as tumor markers should be based on knowledge of their expression pattern in native cancers and related normal tissues, as well as in nonmalignant diseases of the same organs
In light of the biological basis of CA19.9 expression, we propose to extend the idea of personalized medicine to the use of Lewis type carbohydrate antigens as tumor markers in gastrointestinal cancers (Figure 2)
Summary
The outcome of gastrointestinal cancers, in particular pancreatic ductal adenocarcinoma (PDAC), is unfavorable when recognized at an advanced stage. The search for suitable biomarkers for the diagnosis, management and follow-up of gastrointestinal cancers is a relevant challenge of cancer research [1,2,3,4]. Carbohydrate antigen 19.9 (CA19.9) has been widely used to address these aims in both research and clinical practice. It remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged [5] and an unsubstituted tool necessary for any therapeutic choice for patients with advanced pancreatic cancer [6,7,8]. Many other molecules are under investigation as alternatives or complements of CA19.9 [9,10,11].
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