Prognostic Markers in Pancreatic Cancer: the tumor and its environment

Incidence Pancreatic cancer is not one of the most common types of cancer; however it is most certainly one of the most devastating types, ranking fourth in the list of cancer related deaths with a 5-year survival of only 6%. In 2010 there were an estimated 43.140 new cases whereas 36.800 patients were expected to die from this disease in the United States. Worldwide, the expected numbers were 278.684 new cases and 266.669 deaths. In the Netherlands 2481 patients died of pancreatic cancer in 2010. Interestingly, whereas for most cancers, death rates have decreased over the years, those of pancreatic cancer have remained relatively stable. Pathogenesis In order to effectively diagnose, prevent and treat pancreatic cancer, a detailed understanding of the molecular biology of this disease is required. Like many other cancers, pancreatic cancer results from the accumulation of genetic alterations. It originates in the ductal epithelium and evolves from non-invasive precursor lesions of which pancreatic intraepithelial neoplasias (PanINs) are the best characterized. The progression from minimally dysplastic epithelium (PanIN grade 1) to more severe dysplasia (PanIN grades 2 and 3) and finally to invasive carcinoma is paralleled by the successive accumulation of genetic alterations of which some appear earlier than others (figure 1). A brief overview of the molecular mechanisms underlying the biology of pancreatic cancer is given in chapter 2.

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