Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Cancer Causes & Control
Published in: Cancer Causes & Control 2/2019

01-02-2019 | Prostate Cancer | Original Paper

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

Authors: Adrian Rosenberg, Oluwarotimi S. Nettey, Pooja Gogana, Ujalla Sheikh, Virgilia Macias, Andre Kajdacsy-Balla, Roohollah Sharifi, Rick A. Kittles, Adam B. Murphy

Published in: Cancer Causes & Control | Issue 2/2019

Login to get access

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.
Literature
1.
Hollis BW, Marshall DT, Savage SJ, Garrett-Mayer E, Kindy MS, Gattoni-Celli S (2013) Vitamin D3 supplementation, low-risk prostate cancer, and health disparities. J Steroid Biochem Mol Biol 136:233PubMedCrossRef
2.
Ginde AA, Liu MC, Camargo CA Jr (2009) Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med 169(6):626PubMedCentralPubMedCrossRef
3.
Li H, Stampfer MJ, Hollis JBW, Mucci LA, Gaziano JM, Hunter D, Giovannucci EL, Ma J (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer (VD, VDR variation, and prostate cancer). PLoS Med 4(3):e103PubMedCentralPubMedCrossRef
4.
5.
Nyame YA, Murphy AB, Bowen DK, Jordan G, Batai K, Dixon M, Hollowell CMP, Kielb S, Meeks JJ, Gann PH et al (2016) Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. J Clin Oncol 34(12):1345PubMedCentralPubMedCrossRef
6.
Murphy AB, Kelley B, Nyame YA, Martin IK, Smith DJ, Castaneda L, Zagaja GJ, Hollowell CMP, Kittles RA (2012) Predictors of serum vitamin D levels in African American and European American men in Chicago. Am J Men Health 6(5):420CrossRef
7.
Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering GE, Fraser WD, Sterne JA, Metcalfe C (2011) Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes Control 22(3):319–340PubMedCrossRef
8.
Shakira MN, Ken B, Chiledum A, Tanya A-C, Rick AK (2016) Association between serum 25-hydroxy-vitamin D and aggressive prostate cancer in African American men. Nutrients 9(1):12CrossRef
9.
Holick MF: High prevalence of vitamin D inadequacy and implications for health. Mayo Clinic Proc 2006, 81(3):353CrossRef
10.
Swami S, Krishnan AV, Wang JY, Jensen K, Horst R, Albertelli MA, Feldman D (2012) Dietary vitamin D3 and 1,25-dihydroxyvitamin D3 (calcitriol) exhibit equivalent anticancer activity in mouse xenograft models of breast and prostate cancer. Endocrinology 153(6):2576PubMedCentralPubMedCrossRef
11.
Woo TCS, Choo R, Jamieson M, Chander S, Vieth R (2005) Pilot study: potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. Nutr Cancer 51(1):32PubMedCrossRef
12.
Wagner D, Trudel D, Van Der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K et al (2013) Randomized clinical trial of Vitamin D 3 doses on prostatic Vitamin D metabolite levels and Ki67 labeling in prostate cancer patients. J Clin Endocrinol Metab 98(4):1498PubMedCrossRef
13.
Barreto AM, Schwartz GG, Woodruff R, Cramer SD (2000) 25-Hydroxyvitamin D3, the prohormone of 1,25-dihydroxyvitamin D3, inhibits the proliferation of primary prostatic epithelial cells. Cancer Epidemiol Biomarker Prev 9(3):265. A publication of the American Association for Cancer Research, cosponsored by The American Society of Preventive Oncology
14.
Marshall D, Savage SJ, Garrett-Mayer E, Keane T, Hollis B, Horst R, Ambrose LH, Kindy MS, Gattoni-Celli S (2012) Vitamin D-3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. J Clin Endocrinol Metab 97(7):2315
15.
Peehl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D (1994) Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Can Res 54(3):805
16.
Zhao XY, Peehl DM, Navone NM, Feldman D (2000) 1α,25-dihydroxyvitamin d 3 inhibits prostate cancer cell growth by androgen-dependent and androgen-independent mechanisms. Endocrinology 141(7):2548PubMedCrossRef
17.
Liu G, Oettel K, Ripple G, Staab MJ, Horvath D, Alberti D, Arzoomanian R, Marnocha R, Bruskewitz R, Mazess R et al (2002) Phase I trial of 1α-hydroxyvitamin D 2 in patients with hormone refractory prostate cancer. Clin Cancer Res 8(9):2820PubMed
18.
Gross C, Stamey T, Hancock S, Feldman D (1998) Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol). J Urol 159(6):2035PubMedCrossRef
19.
Beer TM, Lemmon D, Lowe BA, Henner WD (2003) High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma. Cancer 97(5):1217PubMedCrossRef
20.
Trump DL, Potter DM, Muindi J, Brufsky A, Johnson CS (2006) Phase II trial of high-dose, intermittent calcitriol (1,25 dihydroxyvitamin D3) and dexamethasone in androgen-independent prostate cancer. Cancer 106(10):2136PubMedCrossRef
21.
Krishnan A, Feldman D (2010) Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment. Endocr Relat Cancer 17(1):R19PubMedCrossRef
22.
Beer TM, Myrthue A, Garzotto M, Hara MF, Chin R, Lowe BA, Montalto MA, Corless CL, Henner WD (2004) Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy. Cancer Epidemiology Biomarkers & Prevention 13(12):2225 A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology
23.
Moreno J, Krishnan AV, Feldman D (2005) Molecular mechanisms mediating the anti-proliferative effects of Vitamin D in prostate cancer. J Steroid Biochem Mol Biol 97(1):31PubMedCrossRef
24.
Plum L, De Luca H (2009) The functional metabolism and molecular biology of vitamin D action. Clin Rev Bone Min Metab 7(1):20CrossRef
25.
Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF (1998) Human prostate cells synthesize 1,25-dihydroxyvitamin D 3 from 25-hydroxyvitamin D 3. Cancer Epidemiol Biomarkers Prev 7(5):391PubMed
26.
Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124(3):453PubMedCrossRef
27.
Block G, Hartman AM, Naughton D (1990) A reduced dietary questionnaire: development and validation. Epidemiology 1(1):58PubMedCrossRef
28.
Epstein J, Egevad L, Amin MB, Delahunt B, Srigley, Jr, Humphrey PA: The 2014 International Society of Urological Pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 2016, 40(2):244PubMed
29.
Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW et al (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3):428PubMedCrossRef
30.
Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P, Mihatsch MJ (1996) Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol 178(4):437PubMedCrossRef
31.
Verma R, Gupta V, Singh J, Verma M, Gupta G, Gupta S, Sen R, Ralli M (2015) Significance of p53 and ki-67 expression in prostate cancer (original article) (clinical report). Urol Ann 7(4):488PubMedCentralPubMedCrossRef
32.
Pascale M, Aversa C, Barbazza R, Marongiu B, Siracusano S, Stoffel F, Sulfaro S, Roggero E, Bonin S, Stanta G: The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients. Radiol Oncol. 50; 2016: 313PubMedCentralPubMedCrossRef
33.
Fisher G, Yang ZH, Kudahetti S, Møller H, Scardino P, Cuzick J, Berney DM (2013) Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort. Br J Cancer 108(2):271PubMedCentralPubMedCrossRef
34.
Zellweger T, Günther S, Zlobec I, Savic S, Sauter G, Moch H, Mattarelli G, Eichenberger T, Curschellas E, Rüfenacht H et al (2009) Tumour growth fraction measured by immunohistochemical staining of Ki67 is an independent prognostic factor in preoperative prostate biopsies with small-volume or low-grade prostate cancer. Int J Cancer 124(9):2116PubMedCrossRef
35.
Richards Z, Batai K, Farhat R, Shah E, Makowski A, Gann PH, Kittles R, Nonn L (2017) Prostatic compensation of the vitamin D axis in African American men. JCI Insight 2(2):e91054PubMedCentralPubMedCrossRef
36.
Medioni J, Deplanque G, Ferrero J-M, Maurina T, Rodier J-MP, Raymond E, Allyon J, Maruani G, Houillier P, Mackenzie S et al (2014) Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients. Clin Cancer Res 20(17):4471PubMedCrossRef
37.
Chan JS, Beer TM, Quinn DI, Pinski JK, Garzotto M, Sokoloff M, Dehaze DR, Ryan CW (2008) A phase II study of high-dose calcitriol combined with mitoxantrone and prednisone for androgen-independent prostate cancer. BJU Int 102(11):1601PubMedCrossRef
38.
Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM et al (2007) Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol 25(6):669PubMedCrossRef
39.
Chan JM, Stampfer MJ, Ma J, Gann PH, Gaziano JM, Giovannucci EL (2001) Dairy products, calcium, and prostate cancer risk in the physician’s; health study. Am J Clin Nutr 74(4):549PubMedCrossRef
40.
Batai K, Murphy AB, Ruden M, Newsome J, Shah E, Dixon MA, Jacobs ET, Hollowell CMP, Ahaghotu C, Kittles RA (2017) Race and BMI modify associations of calcium and vitamin D intake with prostate cancer. BMC Cancer 17(1)
41.
Malhotra S, Lapointe J, Salari K, Higgins JP, Ferrari M, Montgomery K, van de Rijn M, Brooks JD, Pollack JR (2011) A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer (prostate cancer proliferation index). PLoS ONE 6(5):e20293PubMedCentralPubMedCrossRef
42.
Krishnan AV, Feldman D (2011) Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol 51:311PubMedCrossRef
43.
Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ (2014) The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 14:342PubMedCrossRef
44.
Robsahm TE, Schwartz GG, Tretli S (2013) The Inverse relationship between 25-hydroxyvitamin D and cancer survival: discussion of causation. Cancers 5(4):1439PubMedCentralPubMedCrossRef
Metadata
Title
Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients
Authors
Adrian Rosenberg
Oluwarotimi S. Nettey
Pooja Gogana
Ujalla Sheikh
Virgilia Macias
Andre Kajdacsy-Balla
Roohollah Sharifi
Rick A. Kittles
Adam B. Murphy
Publication date
01-02-2019
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 2/2019
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-019-1128-2

Other articles of this Issue 2/2019

Cancer Causes & Control 2/2019 Go to the issue

Brief Report

Identifying optimal approaches to scale up colorectal cancer screening: an overview of the centers for disease control and prevention (CDC)’s learning laboratory

Original Paper

The Be-Well Study: a prospective cohort study of lifestyle and genetic factors to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer

Original Paper

Trends in lobular carcinoma in situ management: endocrine therapy use in California and New Jersey

Brief report

Non-alcoholic fatty liver disease and colorectal cancer survival

Correction

Correction to: The relationship between diabetes, prostate-specific antigen screening tests, and prostate cancer

Original Paper

Predictors of breast cancer mortality among white and black women in large United States cities: an ecologic study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits