Presentation Authors: Farzana Faisal*, Harsimar Kaur, Baltimore, MD, Jeffrey Tosoian, Scott Tomlins, Ann Arbor, MI, Edward Schaeffer, Chicago, IL, Tamara Lotan, Baltimore, MD
Introduction: The SPINK1 molecular subtype has been shown to be more common in African American (AA) men with prostatic adenocarcinoma (PCa) than European Americans (EA). Studies have suggested that SPINK1 expression is associated with more aggressive disease. However, the size, follow-up, and racial diversity of prior patient cohorts have limited our understanding of the impact of SPINK1 expression in clinically localized PCa. The objective was to determine the associations between SPINK1 subtype, race, and clinical and pathologic outcomes after radical prostatectomy (RP).
Methods: A total of 186 AA and 206 EA men who underwent RP at Johns Hopkins were matched according to pathologic Gleason grade. We examined SPINK1 status by immunohistochemistry on tissue microarrays using a genetically validated assay. SPINK1 prevalence was compared between races. Logistic regression and Cox proportional hazard analyses assessed the association of SPINK1 status with pathologic and oncologic outcomes in race-specific multivariate models. A second objective was to determine any correlation between CD3 and CD8 T-cell densities with SPINK1 status and race, using immunostaining and automated image analysis of lymphocytes.
Results: SPINK1-positive subtype was present in 25% (45/186) of AA and 15% (30/206) of EA men (p=0.013), and AA race was a predictor of SPINK1-positive subtype on multivariate analysis (OR 2.07, 95% CI 1.22-3.49, p=0.007). There were no differences in pathologic grade group (GG), pathologic stage, biochemical recurrence (BCR)-free survival, or metastasis-free survival between SPINK1-positive and SPINK1-negative tumors in the overall cohort or by race. In multivariate analyses, SPINK1 expression was not associated with BCR (AA: HR 0.99, 95% CI 0.56-1.75, p=0.976; EA: HR 0.88, 95% CI 0.43-1.77, p=0.720) or metastasis (AA: HR 0.79, 95% CI 0.25-2.49, p=0.691; EA: HR 1.55, 95% CI 0.58-4.11, p=0.381) in either the AA or the EA cohort. There were no significant differences in surrounding CD3/CD8 lymphocyte densities between SPINK1-positive and SPINK1-negative tumors in either race.
Conclusions: SPINK1-positive subtype is more prevalent in AA than EA men with PCa. While previous studies showed that SPINK1 may be associated with more aggressive PCa, we found that SPINK1 protein expression was not associated with worse pathologic or oncologic outcomes including BCR and metastasis after RP in either AA men or EA men.
Source of Funding: DOD/CDMRP