Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression

Abstract

PurposeData suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies.Patients and MethodsWe examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI.ResultsMen whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression.ConclusionHigh VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression.

ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer

“…SOX9 IHC and ERG fusion status in PCa tissue microarrays. IHC was performed on tissue microarrays (TMAs) created from prostatectomy samples among men with prostate cancer in the Physicians' Health and Health Professionals Follow-up Studies tumor cohort as described in detail in 2 recent publications (42,48). IHC was performed on 5-micron sections of 6 TMAs using the SOX9 antibody as described above.…”

“…To determine whether SOX9 protein expression also correlated with TMPRSS2:ERG fusion, we carried out SOX9 immunohistochemical (IHC) assessment on a primary PCa tissue microarray from the Physicians' Health and Health Professionals Follow-up Studies, which had been assessed previously for TMPRS-S2:ERG fusion by FISH and IHC (42,43). Each tumor was scored based on staining intensity and fraction of cells that were positive (SOX9 addscore; representative SOX9-positive and -negative staining is shown in Supplemental Figure 1B).…”

Markers of Vitamin D Exposure and Esophageal Cancer Risk: A Systematic Review and Meta-analysis

“…It had previously been suggested that apoptosis mechanisms were important for the transformation of Barrett's esophagus into adenocarcinoma and that expression of VDR in the esophagus was important in regulating apoptosis (70). It has further been shown that high expression of VDR can impact disease progression and overall survival of prostate, colon, and breast cancers (65,67,71). In a very small study by…”

Reposição de vitamina D nativa: indicação à luz das evidências científicas atuais

“…Por exemplo, experimentos in vitro mostram os efeitos do calcitriol na inibição da angiogênese (redução de interleucina-8, fator induzido por hipóxia α-1 e fator de crescimento endotelial vascular) e proliferação (redução da matriz metaloproteinase-9 e ativador do plasminogênio, aumento de p21 e p27) em linhagens de células neoplásicas de mama, próstata e colo. [50][51][52][53] Em linha com os efeitos descritos, pacientes com tumores de próstata ou mama que possuem uma maior expressão do receptor para vitamina D (VDR) apresentam melhor sobrevida. [54][55][56] Embora estudos epidemiológicos apontem para uma relação entre deficiência de vitamina D e aumento da incidência de câncer, e estudos em animais e com cultivo celular reforcem essa relação, dados obtidos a partir de estudos clínicos são inconsistentes.…”