Among all human
carcinomas, pancreatic cancer has one of the worst survival rates. Most patients will die of this
cancer shortly after diagnosis, and currently, surgery is the only potential cure. Ductal
adenocarcinoma is the most common histologic type. The search for prognostic parameters has progressed from mere physical or histomorphological
tumor properties to molecular parameters. These, in turn, might point toward new therapeutic strategies. The K-ras oncogene is known to play a role in early stages of ductal
adenocarcinoma carcinogenesis, and ras homologues are differentially expressed in cancerous versus normal ductal cells. RhoA belongs to a family of ras homologues comprising RhoA, RhoB, and RhoC. It is a
guanosine triphosphatase associated with the cytoskeleton that seems to be involved in epithelial mesenchymal transition, a process of dedifferentiation. Immunohistologic RhoA expression was studied in a tissue microarray of 94 pancreatic ductal
adenocarcinomas and correlated with clinicopathologic parameters and follow-up.
RhoA protein expression, measured as labeling intensity or evaluated as percentage of reactive
tumor cells, correlated with overall survival. A multivariate analysis demonstrated that
RhoA protein expression is independent from other known prognostic parameters such as
tumor size or grade. Moreover, a score combining RhoA expression with
tumor size and grade resulted in a highly significant increase in the prognostic value for the overall survival of patients with pancreatic ductal
adenocarcinoma.