Dohn Line Hammer, Illemann Martin, Høyer-Hansen Gunilla, Christensen Ib J, Hostmark Jens, Litlekalsoy Jorunn, von der Maase Hans, Pappot Helle, Laerum Ole D
Department of Oncology, Rigshospitalet, Copenhagen, Denmark; The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Urol Oncol. 2015 Apr;33(4):165.e15-24. doi: 10.1016/j.urolonc.2014.12.001. Epub 2015 Jan 6.
To evaluate the expression-and localization pattern of the urokinase-type plasminogen activator receptor (uPAR), focusing on its clinical implications in patients with urothelial neoplasia of the bladder treated with radical cystectomy. uPAR is a central molecule in tissue remodeling during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia.
The expression-and localization pattern of uPAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages, and myofibroblasts at the invasive front and tumor core, respectively. Statistical analyses were performed to evaluate the association of uPAR localization and score with clinicopathologic covariates and survival.
uPAR positivity was seen in 122/137 (89%) and 118/149 (74%) of the neoplasias at the invasive front and tumor core, respectively. uPAR was primarily expressed by myofibroblasts and macrophages in the surrounding stroma as well as some cancer cells. A significant association between uPAR positivity and T-stage as well as grade was found for all 3 cell types in tumor core (P ≤ 0.04 for all comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020).
The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly invasive tumors that could benefit from additional chemotherapy or more intensive follow-up after cystectomy.
评估尿激酶型纤溶酶原激活物受体（uPAR）的表达及定位模式，重点关注其在接受根治性膀胱切除术的膀胱尿路上皮肿瘤患者中的临床意义。uPAR是癌症侵袭和转移过程中组织重塑的核心分子，也是一种公认的癌症预后标志物。uPAR在膀胱尿路上皮肿瘤中的表达、定位及其预后意义仅得到有限的研究。
研究1988年至2005年间接受根治性膀胱切除术的149例患者福尔马林固定石蜡包埋肿瘤组织中uPAR的表达及定位模式。通过免疫组织化学测定uPAR表达，并分为阴性或阳性。分别获取侵袭前沿和肿瘤核心处癌细胞、巨噬细胞及肌成纤维细胞的单独数值。进行统计分析以评估uPAR定位和评分与临床病理协变量及生存的相关性。
侵袭前沿和肿瘤核心处分别有122/137（89%）和118/149（74%）的肿瘤显示uPAR阳性。uPAR主要由周围基质中的肌成纤维细胞和巨噬细胞以及部分癌细胞表达。在肿瘤核心处，所有3种细胞类型的uPAR阳性与T分期及分级之间均存在显著相关性（所有比较P≤0.04）。单因素分析中，uPAR阳性组的生存期短于uPAR阴性组（风险比=2.39；95%置信区间：1.15 - 5.01；P = 0.020）。
uPAR的表达可能是一种预后标志物，有助于识别侵袭性强、高度浸润性肿瘤患者，这些患者可能从额外的化疗或膀胱切除术后更密切的随访中获益。
