Bauman Tyler M, Becka Alexander J, Sehgal Priyanka D, Huang Wei, Ricke William A
Division of Urologic Surgery, Department of Surgery, Washington University in St Louis School of Medicine, St Louis, MO.
Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Hum Pathol. 2015 Nov;46(11):1744-51. doi: 10.1016/j.humpath.2015.07.015. Epub 2015 Jul 29.
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.
单免疫球蛋白白细胞介素-1相关受体（SIGIRR）是Toll样受体4和白细胞介素-1介导的活化B细胞核因子κ轻链增强子激活的负调节因子。本研究的目的是定性和定量测定人前列腺组织中SIGIRR蛋白的表达，并将SIGIRR表达与临床参数相关联。使用免疫组织化学和多光谱成像对前列腺腺组织中的SIGIRR表达进行定量，并根据良性前列腺增生和前列腺癌（PCa）的临床病理特征评估其表达。采用低Gleason评分（≤6和3+4）和高Gleason评分（4+3和≥8）亚组分析患者预后。SIGIRR主要表达于前列腺上皮细胞的细胞质和细胞核中，在基质中表达较少。与正常前列腺相比，良性前列腺增生、高级别前列腺上皮内瘤变、PCa和转移灶中细胞质SIGIRR表达相似。转移样本中细胞核表达降低（P = 0.04）。SIGIRR表达的变化与Gleason评分、病理分期、肿瘤体积、手术切缘状态或血清前列腺特异性抗原无关（P>0.05）。在单变量分析中，细胞核（P = 0.96）和细胞质（P = 0.89）SIGIRR表达与患者预后无关，但在低Gleason评分患者的分析中，高细胞质SIGIRR表达在单变量（P = 0.01）和多变量（风险比，2.31 [95%置信区间1.05 - 5.06]；P = 0.04）分析中均与生化复发相关。同样，在仅对低分期（pT2）肿瘤的多变量分析中，SIGIRR独立预测生化复发（P = 0.009）。我们得出结论，SIGIRR可预测低Gleason评分和低病理分期PCa患者的生化复发。
