Molecular prognostic markers in pancreatic cancer

Pancreatic cancer has a very poor prognosis and is a common cause of cancer death in the Western world. Certain genetic alterations may be important in the prognosis of pancreatic cancer. Activation mutations in the K‐ras oncogene occur in around 90% of pancreatic cancers, and the overexpression of growth factors epidermal growth factor (EGF), transforming growth factor (TGF)α, TGFβs 1–3, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and growth factor receptors c‐erbB‐2 and −3 and TGFRβs 1–3 is common. High mutation levels of cell cycle control genes such asp53,p16,p21,SMAD4, and cyclin D1 are found, and there is abnormal expression of apoptotic genes, such asbcl‐2,bcl‐XL, andbax. The expression of several of these growth factors and their receptors has been found to be associated with poorly differentiated tumors of an advanced stage and decreased survival. However, the inactivation and loss of expression ofp16,p53, andp21, and the expression of several apoptotic genes, such asbax andbcl‐2, have not been found to be of any prognostic significance. The expression of wild typep53, however, may predict responsiveness to chemotherapy. TGFβ1 expression has been shown to be associated with longer survival in patients with pancreatic cancer. Two studies (including our own) have foundbcl‐XL expression to be significantly associated with poor survival. These and newer molecular markers may prove to be important in the choice of future therapies for pancreatic cancer.