SIGIRR/TIR8, an important regulator of TLR4 and IL-1R–mediated NF-κB activation, predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas

Authors: Tyler M. Bauman BS^a, Alexander J. Becka BS^b, Priyanka D. Sehgal BS^b, Wei Huang MD^c,d, William A. Ricke PhD^b,d,e

Online: https://www.sciencedirect.com/science/article/abs/pii/S0046817715002634

Issue: Human Pathology, Volume 46, Issue 11, November 2015, Pages 1744-1751

Abstract

Single Ig IL-1–related receptor (SIGIRR) is a negative regulator of toll-like receptor 4 and IL-1–mediated activation of nuclear factor κ–light-chain enhancer of activated B cells. The purpose of this study was to qualitatively and quantitatively determine SIGIRR protein expression in human prostate tissues and associate SIGIRR expression with clinical parameters. SIGIRR expression was quantified in glandular prostate tissue using immunohistochemistry and multispectral imaging, and expression was evaluated in relation to clinicopathological features of benign prostatic hyperplasia and prostate cancer (PCa). Subgroupings of low Gleason score (≤6 and 3 + 4) and high Gleason score (4 + 3 and ≥8) were used for patient outcomes. SIGIRR was predominantly expressed in the cytoplasm and nucleus of the prostatic epithelium with little expression within the stroma. Compared with normal prostate, cytoplasmic SIGIRR expression was similar in benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, PCa, and metastases. A decrease in nuclear expression was found in metastasis samples (P = .04). Changes in SIGIRR expression were not associated with Gleason score, pathological stage, tumor volume, surgical margin status, or serum prostate-specific antigen (P > .05). Nuclear (P = .96) and cytoplasmic (P = .89) SIGIRR expressions were not related to patient outcomes in univariable analysis, but in the analysis of patients with low Gleason scores, high cytoplasmic SIGIRR expression was associated with biochemical recurrence in both univariable (P = .01) and multivariable (hazard ratio, 2.31 [95% confidence interval 1.05-5.06]; P = .04) analyses. Similarly, in multivariable analysis of only low-stage (pT2) tumors, SIGIRR independently predicted biochemical recurrence (P = .009). We conclude that SIGIRR predicts biochemical recurrence in patients with low Gleason score and low pathological stage PCa.

Keywords: SIGIRR, Multispectral imaging, NF-κB, Biomarker, Indolent, Prostate cancer

AUTHOR AFFILIATIONS

1. Division of Urologic Surgery, Department of Surgery, Washington University in St Louis School of Medicine, St Louis, MO
2. Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI
3. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
4. Department of Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI
5. George M. O’Brien Center, University of Wisconsin School of Medicine and Public Health, Madison, WI