Ampullary and pancreatic adenocarcinoma-a comparative study.

Background: Pancreatic ductal adenocarcinoma (PDAC) and ampullary adenocarcinoma (AAC) are 2 gastrointestinal cancers that share overlapping symptoms. Although some studies have proposed the hypothesis of differences in pathogenesis and prognosis in these 2 cancers; they remain treated similarly. The classification of AAC into three subtypes [pancreatobiliary (PB), intestinal (IT) and mixed (M)] is especially crucial for the 3 axes of patients management (diagnosis, prognosis and therapy). Some studies suggest that PB subtype pathogenesis is comparable to PDAC. The objective of this study was to conduct a comparative analysis between PDAC and AAC; notably PB subtype; via mutational status analysis of 3 oncogenes (KRAS, NRAS and BRAF) hoping to consolidate AAC biology understanding.

Methods: Nine hot spot mutation sites of KRAS, NRAS and BRAF were analysed using pyrosequencing in 39 PDAC and 21 AAC from Tunisian patients. Comparative study was performed using SPSS software.

Results: Mutations in oncogenes were detected in almost 43% of AAC, especially in PB (47%) and 95% of PDAC. KRAS was the most mutated oncogene. There were statistical significant differences between PDAC and AAC in tumor differentiation (P<0.001), perineural invasion (P<0.001), vascular emboli (P=0.001), T stage (P=0.007), N stage (P=0.001) and mutational status (P<0.001). When comparing PDAC and PB subtype, there were also significant differences in tumor size (P=0.001), tumor differentiation (P<0.001), perineural invasion (P<0.001), vascular emboli (P=0.001), T stage (P=0.033), N stage (P<0.001) and mutational status (P<0.001).

Conclusions: AAC even PB subtype is different from PDAC. We think that these different tumor types require highly individualized therapy guided by their histomolecular characteristics and that we should stop diagnosing and treating them as a unique entity.