Erlandsson Ann, Carlsson Jessica, Andersson Sven-Olof, Vyas Chraig, Wikström Pernilla, Andrén Ove, Davidsson Sabina, Rider Jennifer R
a Department of Urology, Faculty of Medicine and Health , Örebro University , Örebro , Sweden.
c Department of Environmental and Life Sciences/Biology , Karlstad University , Karlstad , Sweden.
Scand J Urol. 2018 Apr;52(2):129-133. doi: 10.1080/21681805.2017.1421261. Epub 2018 Jan 8.
The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa.
This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category.
There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97).
Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.
本研究旨在通过研究经诊断为局限性前列腺癌（PCa）男性的肿瘤组织中诱导型一氧化氮合酶（iNOS）的免疫反应性，探讨iNOS在致死性前列腺癌中的作用。
本研究嵌套于一组经诊断为偶发性PCa并接受经尿道前列腺切除术的男性队列（瑞典观察等待队列）。为了研究致死性PCa的分子决定因素，选取死于PCa的男性（n = 132）作为病例；对照组（n = 168）包括在随访期间存活至少10年且未死于PCa的PCa男性。前列腺肿瘤上皮细胞和周围基质细胞中iNOS的免疫反应性被评为低/阴性、中度或高度。根据iNOS类别，采用逻辑回归估计致死性PCa的比值比（OR）和95%置信区间（95%CI）。
基质中iNOS免疫反应性与致死性疾病之间无关联。然而，比较上皮细胞中iNOS高免疫反应性与低/阴性免疫反应性时，致死性PCa的OR为3.80（95%CI 1.45 - 9.97）。
局限性PCa患者的预后各不相同，尤其是那些肿瘤中度分化的患者。识别与PCa长期预后相关的因素可以阐明PCa肿瘤生物学并确定新的候选预后标志物。这些发现支持了前列腺肿瘤上皮中高iNOS与致死性疾病相关的假说。
