Background: This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer (PCa), such as ERG rearrangements and PTEN deletions, with oncologic outcomes in PCa patients treated with brachytherapy.
Methods: Ninety-two men underwent I-125 brachytherapy with a 145Gy delivered dose between 2000 and 2008. Pre-treatment prostate biopsies were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for ERG rearrangement and overexpression, PTEN deletion and expression loss. Univariable and multivariable Cox-regression analyses evaluated association of ERG and PTEN status with biochemical recurrence (BCR).
Results: Within a median follow-up of 73 months, 11% of patients experienced BCR. Of 80 samples with both IHC and FISH performed for ERG, 46 (57.8%) demonstrated rearrangement by FISH and 45 (56.3%) by IHC. Of 77 samples with both IHC and FISH for PTEN, 14 (18.2%) had PTEN deletion by FISH and 22 (28.6%) by IHC. No significant associations were found between ERG, PTEN status and clinicopathologic features. Patients with concurrent ERG rearrangement and PTEN deletion demonstrated significantly worse relapse-free survival rates compared to those with ERG or PTEN wild-type (p< 0.01). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, combined ERG rearranged and PTEN deletion was independently associated with BCR (HR 2.6, p=0.02).
Conclusions: Concurrent ERG rearrangement and PTEN loss was independently associated with time to BCR in patients undergoing brachytherapy. Future studies are needed to validate PCa molecular subtyping for risk-stratification.
Impact: Identifying patients in the ERG rearranged/PTEN deleted molecular subclass may improve treatment personalization.
Written by:
Fontugne J, Lee D, Cantaloni C, Barbieri CE, Caffo O, Hanspeter E, Mazzoleni G, Dalla Palma P, Rubin MA, Fellin G, Mosquera JM, Barbareschi M, Demichelis F. Are you the author?
Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York , NY, USA.
Reference: Cancer Epidemiol Biomarkers Prev. 2014 Feb 10. Epub ahead of print.
doi: 10.1158/1055-9965.EPI-13-1180
PubMed Abstract
PMID: 24515272
