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)alpha, TGFbetas 1-3, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and growth factor receptors c-erbB-2 and -3 and TGFRbetas 1-3 is common. High mutation levels of cell cycle control genes such as p53, p16, p21, SMAD4, and cyclin D1 are found, and there is abnormal expression of apoptotic genes, such as bcl-2, bcl-XL, and bax. 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 of p16, p53, and p21, and the expression of several apoptotic genes, such as bax and bcl-2, have not been found to be of any prognostic significance. The expression of wild type p53, however, may predict responsiveness to chemotherapy. TGFbeta1 expression has been shown to be associated with longer survival in patients with pancreatic cancer. Two studies (including our own) have found bcl-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.
Ghaneh
Paula
P
Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, United Kingdom.
Kawesha
Anthony
A
Evans
James D
JD
Neoptolemos
John P
JP
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology; D009857:Oncogenes / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D010960:Plasminogen Activators / Q000235:genetics / Q000502:physiology; D011379:Prognosis; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D006133:Growth Substances; D017978:Receptors, Growth Factor; D010960:Plasminogen Activators