Molecular markers of pancreatic cancer: development and clinical relevance

The prognosis of pancreatic cancer remains poor, mainly because of its aggressive biological behaviour and late clinical diagnosis, which precludes the application of appropriate curative therapies. Therefore, one of the major goals in clinical pancreatology is to find molecular markers, specific and sensitive enough to make an early and correct diagnosis of pancreatic cancer, before it has disseminated and become untreatable.

This overview article explores the potential utility of current molecular markers for the diagnosis of pancreatic cancer.

There is a wide array of serum-based and tissue-based markers for pancreatic cancer. Serum-based molecular markers include CA 19-9, CA 125, M2-PK and secreted proteins. A tissue can be used to test genetic mutations such as K-ras, inactivation of tumour suppressor genes (e.g. p16, p53), mucins, telomerase activity, growth factors, DNA methylation, and global gene expression of cDNA microarrays, mitochondrial mutations and proteomics. None of these markers is currently useful for the detection of early pancreatic cancer. In clinical practice, the most commonly accepted use of CA 19-9 is to assess the prognosis and monitor the response to therapy.

Many molecular markers have been proposed for the early diagnosis of PC, but most are not ready to be included as part of the routine diagnostic algorithm because they still lack sensitivity, specificity or reproducibility. CA 19-9 remains the most useful molecular marker for the diagnosis and follow-up of clinically and radiological evident pancreatic cancer.