Molecular alterations in prostate cancer as diagnostic, prognostic, and therapeutic targets

Abstract

Prostatic adenocarcinoma is extremely common in Western nations, representing the second leading cause of cancer death in American men. The recent application of increasingly sophisticated molecular approaches to the study of prostate cancer in this "postgenomic" era has resulted in a rapid increase in the identification of somatic genome alterations and germline heritable risk factors in this disease. These findings are leading to a new understanding of the pathogenesis of prostate cancer and to the generation of new targets for diagnosis, prognosis, and prediction of therapeutic response. Although we are still in the very early phase of clinical development, some of the molecular alterations identified in prostate cancer are being translated into clinical practice. The purpose of this review is to update the practicing surgical pathologist, and residents-in-training in pathology, regarding recent findings in the molecular pathobiology of prostate cancer. We will highlight some of the somatic molecular alterations associated with prostate cancer development and progression, with a focus on newer discoveries. In addition, recent studies in which new molecular diagnostic approaches have been applied in the clinic will be discussed.

Figure 1

(A) Current guidelines in the management of patients with elevated PSA at the time of screening. (B) The inclusion of molecular testing for prostate cancer markers may help in predicting a positive prostate biopsy, therefore reducing the number of patients that would otherwise enter an “elevated PSA, negative biopsy” loop (Dashed line).