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Background: Prostate cancer (PCa) is clinically and molecularly heterogeneous. Previous work has subtyped PCa on the basis of mutually exclusive genomic alterations in genes such as ERG, ETV1, SPINK1 or their lack thereof (i.e., ‘Triple Negative’, TN). These studies failed to find a link between these alterations and clinical outcomes. Here we evaluate the prognosis based on these PCa subtypes treated by radical prostatectomy with conservative followup.
Methods: Men with NCCN intermediate-high risk localized prostate cancer treated with RP at the Johns Hopkins (1992-2010) with at least 5 years of follow up were identified. Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis detection were included. A case-cohort design was used to randomly sample two cohorts; one enriched with metastasis from the entire cohort (n=319) and one enriched with metastasis from the patients with BCR (n=263). We analyzed Affymetrix Human Exon 1.0 ST GeneChip expression profiles from the two cohorts to perform subtype classification of patient tumors as ERG+, ETS+, SPINK1+ or TN.
Results: Across the two cohorts, 36%, 12%, 9% and 43% of PCa were classified as ERG+, ETS+, SPINK1+, and TN. UVA shows that SPINK1+ tumors were more common in African Americans (OR: 1.7). In patients that developed metastasis, SPINK1+ had an HR of 3.1(p<0.01) for prostate cancer-specific mortality.
Conclusions: SPINK1 overexpression is associated with faster time to PCSM in at risk men with biochemical and clinical recurrence following radical prostatectomy. ERG and ETS alterations are not prognostic for outcome.