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Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):594-600. doi: 10.1158/1055-9965.EPI-13-1180. Epub 2014 Feb 10.

Recurrent prostate cancer genomic alterations predict response to brachytherapy treatment.

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1
Authors' Affiliations: Departments of Pathology and Laboratory Medicine and Urology; Institute for Precision Medicine; Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York; Centre for Integrative Biology, University of Trento; Departments of Medical Oncology, Pathology, and Radiotherapy and Medical Physics, Ospedale Santa Chiara, Trento; and Department of Surgical Pathology, Central Hospital, Bolzano, Italy.

Abstract

BACKGROUND:

This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer, such as ERG rearrangements and phosphatase and tensin homolog gene (PTEN) deletions, with oncologic outcomes in patients with prostate cancer treated with brachytherapy.

METHODS:

Ninety-two men underwent I-125 brachytherapy with a 145 Gy delivered dose between 2000 and 2008. Pretreatment prostate biopsies were analyzed by immunohistochemistry (IHC) and 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 with 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 prostate cancer molecular subtyping for risk stratification.

IMPACT:

Identifying patients in the ERG-rearranged/PTEN-deleted molecular subclass may improve treatment personalization.

PMID:
24515272
PMCID:
PMC4083705
DOI:
10.1158/1055-9965.EPI-13-1180
[Indexed for MEDLINE]
Free PMC Article
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