Trial Information

Refining the Molecular Progression From Intraductal to Invasive Pancreatic Cancer: Correlating Genetic Profiles and Clinicopathological Phenotypes in Sporadic and Familial Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma (PC) is the fourth leading cause of cancer-related death in the
United States.Despite advances in chemotherapeutics and surgical care, the prognosis for PC
patients remains dismal, even following surgery with curative intent. In order to improve
outcomes, the best hope will be to target preinvasive PanIN lesions for screening and
therapy. Prior to this, however, the natural history of PanIN lesions needs to be better
elucidated. A novel model to study PanIN progression is by examination of cases of local
recurrence following surgical resection. We have previously reported our findings from
histopathological review of such cases. Compared to matched controls, locally-recurrent PC
patients were significantly more likely to exhibit a pattern of multifocal, diffuse PanIN in
their original resection tissue. This is similar to the pattern of multifocal PanIN that has
been demonstrated from small prospective screening studies of familial PC kindreds

These analyses support our hypothesis that field carcinogenesis may be an important
mechanism in PC. The objective of our study is to evaluate for pathological and molecular
evidence of a field effect in locallyrecurrent and familial PC. Our first aim is to assess
for distinctive histological features of PanIN within surgical specimens of our two study
groups. Secondly, clonality of multifocal PanIN will be assessed utilizing microarraybased
comparative genomic hybridization (aCGH). Finally, aCGH will also be utilized to evaluate
recurrence mechanism in a set of cases in which both original tumor and recurrence tumor was
resected, allowing for clonal origins to be evaluated.