PATHOBIOLOGY OF CANCER OF THE PANCREAS

The diagnosis of infiltrating adenocarcinoma of the pancreas is associated with an overall 5-year survival of less than 5%. Although surgical resection has improved the prognosis for patients with localized disease, in the absence of ancillary techniques, clinical and pathologic assessment of pancreas cancer fails to predict outcome in many patients. Recent work has focused on the genetic alterations in pancreas cancer, offering the promise of improving our ability not only to predict survival but also to select the most appropriate therapy. The study of genetic alterations in colon cancer, wherein mutations in the oncogene, K-ras, and the loss of functional activity of several tumor suppressor genes is required for progression from small adenoma to invasive carcinoma, has served as a paradigm for the molecular analysis of pancreas cancer. A similar pattern is emerging for pancreas cancer, in that there is apparently progression from intraductal lesions to invasive cancer, and that K-ras, and several tumor suppressor genes, including p53, deleted in colon cancer (DCC), and multiple tumor suppressor-1 (MTS1), are frequent targets of mutation and/or deletion. Cytogenetic studies and molecular studies assessing allelic loss suggest that several additional oncogenes and tumor suppressor genes involved in the pathogenesis of pancreas cancer remain to be discovered. These recent findings enhance our understanding of the etiology of carcinoma of the pancreas, and serve as the basis for the early detection and, potentially, improved treatment of this typically fatal malignancy. (C) 1995 Wiley-Liss, Inc.