Racial disparity in expression of NF-κb and GDF15 in prostate cancer and accompanying benign prostatic epithelium: Dependence on stage and grade

Document Type

Conference Proceeding

Publication Date

3-1-2018

Publication Title

Lab Investig

Abstract

Background: Growth differentiation factor 15 (GDF15, PDF, NAG-1) is a stress-induced anti-inflammatory cytokine with immunomodulatory functions. High GDF15 is associated with prostate cancer progression [PMID:12894347]. NF-κB is a transcription factor of the Rel family that regulates pro-inflammatory gene expression and gets constitutively activated in androgen-independent prostate cancer, increasing anti apoptotic bcl-2 and angiogenesis. Prostatic GDF15 expression had been shown to correlate inversely with inflammatory lesions in the prostate and suppress NF-κB activity [PMID:25327758]. In this study we examined the levels of NF-κB and GDF-15 in tissue microarrays from African-American (AA) and White (W) prostate cancer patients.

Design: TMAs of 161 AA prostatectomies and 205 W were stained with goat polyclonal antibody to GDF15 or rabbit monoclonal antibody to NF-κB. Cases were matched for grade (p=.8) and stage (2, 3a, or 3b) (p=.3); mean W age 62.2, AA age 60.7 (p=.03). The 3-12 evaluable punched cores of PC and benign prostate/case were evaluated by 2 pathologists on a 0-3+ scale. Mann-Whitney test was used for racial disparities. Kruskal-Wallis test was used for stagewise and gradewise comparisons.

Results: Regardless of race, median GDF15 reactivity was 3 in PC and 1 in benign; NF-κB was 1.5 in PC and 1 in benign (all p <.005). GDF15 expression negatively correlated with NF-κB in tumor (r=.207, p=.008) and in all tissues (r=.192, p=.0003) for W but not for AA. For tumor-tumor and benign-benign comparisons of both antigens by race, only benign glands showed a significant difference, with higher NF-κB in benign epithelium of AA men compared to W men (p=.01). 41.4% of AA had reactivity >1 in benign glands but 30.2% of W did (p=.03). Stagewise and gradewise: In W men, GDF15 expression in PC trended from 3 down to 2 with rising stage (p=.02) and from 3 down to 2.5 with grade (p=.58); NF-κB trended from 1.37 up to 2.00 with stage (p=.28) and 1.5 up to 2.25 with grade (p=.07); all 4 of these trends were absent in AA.

Conclusions: GDF-15 and NF-κB protein levels are inversely related in W but not AA men. There was higher NF-κB in benign glands in AA (possibly correlating with AA's more frequent prostatic inflammation [PMID:9605645]), coupled with less of a decrease in GDF15 and less of an increase in NF-κB with worsening tumor in AA. Higher benign gland NF-κB may account for less ability to mount an immune response to cancer in a segment of AA population and may explain their worse cancer outcome.

Volume

98

First Page

357

Last Page

358

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