Relative 8q gain is a poor prognostic factor in the diagnosis of prostate biopsies irrespective of the TMPRSS2-ERG fusion status

Abstract

ETS transcription factor family genes are involved in recurrent genetic rearrangements in prostate carcinoma (PCa). In 50% of PCa patients there is a fusion between the androgen-regulated elements of TMPRSS2 with the ETS transcription factor ERG, causing over-expression of the latter. Other ETS family genes, namely ETV1, ETV4, and ETV5, have more rarely been found to be fused with TMPRSS2 or other 50 partners. We have previously demonstrated that TMPRSS2-ERG is present in pre-malignant prostate lesions in addition to PCa and that relative 8q gain detected in diagnosis needle biopsies is an independent predictor of disease-specific survival. In order to evaluate the prognostic value of these two alterations, we have analyzed a consecutive series of 200 PCa patients by fluorescence in situ hybridization (FISH) assays in paraffin-embedded diagnostic needle biopsies collected from 1997 to 2001. Most of the biopsies displayed Gleason scores (GS) equal to 7 (40.9%) or higher (47%), with the remaining tumors graded with Gleason scores lower than 7 (12.1%). The fusion gene TMPRSS2eERG was detected in 43.2% of PCa cases, being less frequent in higher GS PCa biopsies (54.2%, 50.6%, and 33.3% for GS ! 7, GS 5 7, and GS O 7, respectively; P 5 0.035). On the other hand, relative 8q gain was less frequent in lower GS PCa biopsies (8.3%, 50.6%, 57% for GS ! 7, GS 5 7, and GS O 7, respectively; P ! 0.01). ERG rearrangements alone were not associated with clinical outcome, whereas 8q gain predicted a worse prognosis in PCa patients irrespective of the TMPRSS2eERG fusion status. The prognostic value of relative 8q gain was independent of clinical variables in a multivariate analysis. To the best of our knowledge, this is the first study combining the aforementioned genetic aberrations to assess its prognostic value. The use of genetic prognostic markers in diagnostic prostate biopsies might impact decision making and has, therefore, the potential to become a common procedure in clinical practice. ANALYSIS OF ALTERNATIVE MECHANISMS FOR RET GENE ACTIVATION IN HEREDITARY AND SPORADIC MEDULLARY THYROID CARCINOMA