Serum carbohydrate antigen 19‐9 in pancreatic adenocarcinoma: a mini review for surgeons

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Monoclonal antibodies against the epitope of a sialic acid closely related to the Lewis blood group antigen system were isolated over 30 years ago when murine splenocytes were immunized with human cancer cell lines.1 This sialic acid is known as the Sialyl Lewis A antigen or carbohydrate antigen 19‐9 (CA19‐9).
CA19‐9 is normally embedded on cell surfaces as gangliosides and mucins on epithelial cells of the biliary tract, pancreatic ducts, stomach and prostate.4 It is also present in low concentrations in the serum, glycosylated on mucins, kininogen and apolipoproteins.6 Extensive research on the biological functions of sialic acids have shown that CA19‐9 is involved in cell growth and differentiation,9 signal transduction,10 apoptosis,11 spermatogenesis12 and immunomodulation.13 Specifically, CA19‐9 has been reported to propagate leukocyte recruitment by mediating adhesion and migration of leukocytes to an inflammatory focus.14
In a pathological state, abnormal sialic acid glycosylation of mucins can alter the molecular microenvironment and promote proliferation, invasion and metastasis.13 CA19‐9 is suspected to play a vital role in malignant cell adhesion to endothelial cells, transmigration and development of metastases. This is supported by in vivo observations of patients with pancreatic cancer,15 colorectal cancer16 and breast cancer,17 whereby elevated CA19‐9 is associated with disease progression and inferior outcomes.
Pancreatic cancer accounts for the seventh highest rate of death from cancer worldwide. In 2012, there were an estimated 338 000 new diagnoses and 330 000 deaths internationally from pancreatic cancer and this is projected to rise annually.18 Due to the late presentations of patients with pancreatic cancer, only 10–20% will undergo potentially curative surgery supplemented by adjuvant chemotherapy. Contributing factors to poor prognosis include the tendency for pancreatic cancer to metastasize early, difficulties in differentiating benign and malignant pancreatic lesions and the limited effectiveness of systemic therapies. Despite advancement in surgical techniques, peri‐operative care as well as therapeutic options, improvement in 5‐year survival rates is marginal.19
The diagnosis and staging of pancreatic lesions is dependent on multiple imaging modalities including ultrasonography, computed tomography (CT), magnetic resonance imaging, positron emission topography, endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography. Serum CA19‐9 is often requested by clinicians in conjunction with these investigations.
The interpretation of CA19‐9 levels is often challenging and the utility of this biomarker in the screening, diagnosis, assessment of resectability and prognostication of pancreatic cancer is often unclear. In this review, we present an appraisal of serum CA19‐9 (referred to as CA19‐9) and its clinical utility.
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