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Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients

Abstract

Purpose

To investigate the correlation between serum 25 hydroxyvitamin D, prostatic 25 hydroxyvitamin D, and serum 1,25 dihydroxyvitamin D, and their respective associations with prostatic tumor proliferation at the time of radical prostatectomy.

Methods

In this cross-sectional analysis of 119 men undergoing radical prostatectomy, serum from whole blood and expressed prostatic fluid was collected on the day of surgery. Tumor proliferation was measured in the dominant tumor on formalin-fixed prostatectomy tissues by immunohistochemical staining for Ki67 and quantified by Aperio imaging analysis.

Results

The sample included 88 African Americans (74%) and 31 (26%) European Americans. Serum and prostatic levels of 25 hydroxyvitamin D were correlated with each other (Spearman’s rho (ρ) = 0.27, p = 0.004), and there was also a correlation between serum 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D (ρ = 0.34, p < 0.001).

Serum and prostatic 25 hydroxyvitamin D levels were not correlated with Ki67 staining in tumor cells. Serum 1,25 dihydroxyvitamin D was inversely correlated with Ki67 staining in tumor cells (ρ = − 0.30, p = 0.002). On linear regression, serum 1,25 dihydroxyvitamin D was negatively associated with Ki67 staining in tumor cells (β − 0.46, 95% CI − 0.75, − 0.04, p = 0.04).

Conclusion

The correlation between physiologic serum levels of 25 hydroxyvitamin D with both prostatic 25 hydroxyvitamin D and serum 1,25 dihydroxyvitamin D suggests that serum levels are reasonable biomarkers of vitamin D status. Furthermore, serum 1,25 dihydroxyvitamin D has an inverse association with Ki67 staining in tumor cells at physiologic levels and may protect against tumor progression.

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Acknowledgments

The authors thank the patients, urologists, pathologists and staff at Jesse Brown VA Medical Center for facilitating patient recruitment and specimen acquisition. We thank the Research Histology and Tissue Imaging core at the University of Illinois at Chicago for assistance with staining, image processing, and analysis.

Funding

Funding was provided by U.S. Department of Veterans Affairs (Grant No. IK2CX000926-01).

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Correspondence to Adam B. Murphy.

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Rosenberg, A., Nettey, O.S., Gogana, P. et al. Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients. Cancer Causes Control 30, 207–214 (2019). https://doi.org/10.1007/s10552-019-1128-2

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Keywords

  • Prostate cancer
  • Vitamin D deficiency
  • Proliferation
  • African American