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SPINK1 expression is enriched in African American prostate cancer but is not associated with altered immune infiltration or oncologic outcomes post-prostatectomy

Prostate Cancer and Prostatic Diseases volume 22, pages 552–559 (2019)Cite this article

Subjects

Abstract

Background

The SPINK1 molecular subtype is 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 SPINK1 expression in AA men. The objective was to determine the associations between SPINK1 subtype, race, and oncologic outcomes after radical prostatectomy (RP).

Methods

A total of 186 AA and 206 EA men who underwent RP were matched according to pathologic grade. We examined SPINK1 status by immunohistochemistry on tissue microarrays using a genetically validated assay. Cox proportional hazard analyses assessed the association of SPINK1 status with oncologic outcomes in race-specific multivariate models. A second objective was to determine the correlation between CD3/CD8 T cell densities with SPINK1 status and race, using immunostaining and automated image analysis.

Results

SPINK1-positive subtype was present in 25% (45/186) of AA and 15% (30/206) of EA men (p = 0.013). There were no differences in pathologic grade, 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 AA or EA men. 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. Contrary to previous studies, we found that SPINK1 protein expression was not associated with worse pathologic or oncologic outcomes after RP in either AA men or EA men.

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Acknowledgements

This work was supported in part by the Department of Defense (PC141474 to EMS, SAT, and TLL).

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Authors and Affiliations

  1. Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Farzana A. Faisal & Tamara L. Lotan

  2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Harsimar B. Kaur & Tamara L. Lotan

  3. Department of Urology, University of Michigan, Ann Arbor, MI, USA

    Jeffrey J. Tosoian & Scott A. Tomlins

  4. Department of Pathology, University of Michigan, Ann Arbor, MI, USA

    Scott A. Tomlins

  5. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Edward M. Schaeffer

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Correspondence to Farzana A. Faisal.

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Conflict of interest

SAT has received travel support from and had a sponsored research agreement with Compendia Bioscience/Life Technologies/Thermo Fisher Scientific, which assisted in the design of the custom RNAseq panel. The University of Michigan has been issued patents on ETS gene fusions in prostate cancer, on which SAT is a coinventor. The diagnostic field of use was licensed to Hologic/Gen-Probe Inc., which has sublicensed rights to Roche/Ventana Medical Systems. SAT has served as a consultant for and received honoraria from Janssen, AbbVie, Sanofi, Almac Diagnostics, and Astellas/Medivation. SAT has sponsored research agreements with Astellas/Medivation and GenomeDX. SAT is an equity holder in and employee of Strata Oncology. TLL has received research funding from Roche/Ventana Medical Systems for other projects and has served as a consultant for and received an honorarium from Janssen. The remaining authors declare that they have no conflict of interest.

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Faisal, F.A., Kaur, H.B., Tosoian, J.J. et al. SPINK1 expression is enriched in African American prostate cancer but is not associated with altered immune infiltration or oncologic outcomes post-prostatectomy. Prostate Cancer Prostatic Dis 22, 552–559 (2019). https://doi.org/10.1038/s41391-019-0139-0

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