Molecular pathology of invasive carcinoma

Abnormalities of several oncogenes and tumor Suppressor genes have been identified in carcinomas of the pancreas during the last decade;, and multiple genetic changes have been demonstrated in individual carcinomas. The variety of genetic,changes suggests that multiple etiologic factors: contribute to carcinogenesis in the pancreas. Several of these changes are characteristically found in specific types of tumors, suggesting that different causes and molecular mechanisms are involved. One example is the loss of heterozygosity at the von Hippel-Lindau (VHL) gene locus in both wild type and hereditary serous cystadenomas,and another is the virtual absence of K-ras mutation and p53 abnormalities in;acinar cell carcinomas, whereas both are;frequently found in ductal adenocarcinomas. Multiple lines of evidence place K-ras mutation very early and loss of p53 and p16 as late events during ductal cell carcino-genesis. The timing and order of other genetic changes such as loss of the DPC4 tumor suppressor function is less certain.