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

Farzana A. Faisal, Harsimar B. Kaur, Jeffrey J. Tosoian, Scott A. Tomlins, Edward M. Schaeffer, Tamara Lotan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalProstate Cancer and Prostatic Diseases
DOIs
StatePublished - Jan 1 2019

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Prostatectomy
African Americans
Prostatic Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Recurrence
Survival
Neoplasms
Multivariate Analysis
Cell Count
Immunohistochemistry
Lymphocytes
T-Lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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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. / Faisal, Farzana A.; Kaur, Harsimar B.; Tosoian, Jeffrey J.; Tomlins, Scott A.; Schaeffer, Edward M.; Lotan, Tamara.

In: Prostate Cancer and Prostatic Diseases, 01.01.2019.

Research output: Contribution to journalArticle

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title = "SPINK1 expression is enriched in African American prostate cancer but is not associated with altered immune infiltration or oncologic outcomes post-prostatectomy",
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.",
author = "Faisal, {Farzana A.} and Kaur, {Harsimar B.} and Tosoian, {Jeffrey J.} and Tomlins, {Scott A.} and Schaeffer, {Edward M.} and Tamara Lotan",
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journal = "Prostate Cancer and Prostatic Diseases",
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T1 - SPINK1 expression is enriched in African American prostate cancer but is not associated with altered immune infiltration or oncologic outcomes post-prostatectomy

AU - Faisal, Farzana A.

AU - Kaur, Harsimar B.

AU - Tosoian, Jeffrey J.

AU - Tomlins, Scott A.

AU - Schaeffer, Edward M.

AU - Lotan, Tamara

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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