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The importance of testing ERG gene fusion status in prostate cancer

Recurrent gene rearrangements were traditionally thought to be critical cancer-causing mechanisms for hematologic and soft tissue malignancies, especially leukemias and lymphomas. However, recent studies have unveiled that even a highly prevalent solid epithelial malignancy, such as prostate cancer, is no exception. It is now estimated that majority of prostate cancers develop and progress due to an underlying genetic defect in which an androgen hormone regulated gene, TMPRSS2, fuses with oncogene ERG, a member of the ETS gene family. These gene fusions are believed to drive the over-expression of ERG leading eventually to uncontrolled growth of prostate cancer.

Since their discovery in 2005, ERG gene fusions have gained significant recognition as a prostate cancer specific biomarker. This biomarker is seldom found in normal tissue or in non-prostatic tumors. ERG alteration is seen in 50% of prostate cancers and 20% of high-grade prostatic intraepithelial neoplasia, a neoplastic precursor lesion that intermingles with prostate carcinoma. Among PSA-screened men in the United States, TMPRSS2-ERG fusion prostate cancer has a prevalence of 46% in prostate needle biopsies. Therefore early detection of ERG over-expression may provide significant diagnostic and prognostic value.

ERG gene fusions can be detected by variety of laboratory based techniques. In addition to looking at a genetic defect directly at the cellular level, antibody-based detection of these gene fusions using immunohistochemistry techniques is available. Antibody-based detection of ERG protein expression is specific for carcinoma, and positive immunostaining usually supports the diagnosis of cancer when examined in context of appropriate morphology. Pathologists can now incorporate this biomarker in the setting of multiplex immunohistochemical markers for optimal evaluation of prostate needle biopsies.

ERG gene fusions along with other promising biomarkers such as PTEN deletion may also provide useful information related to aggressiveness of prostate cancer and in the future are likely going to assist treatment decisions. Emerging studies also suggest that the determination of ERG gene fusion status may be an important therapeutic target. So, in summary, the determination of ERG gene fusion status may provide significant diagnostic, prognostic or theranostic information for patients with prostate cancer.