Life and Health Sciences Research Institute-ICVS, University of Minho, Braga, Portugal.
Virchows Arch. 2013 Apr;462(4):445-53. doi: 10.1007/s00428-013-1388-2. Epub 2013 Mar 6.
Urothelial bladder cancer (UBC) is a heterogeneous type of disease. It is urgent to screen biomarkers of tumour aggressiveness in order to clarify the clinical behaviour and to personalize therapy in UBC patients. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor, and its downregulation is associated with metastatic events in an increasing number of solid tumours. We evaluated the clinical and prognostic significance of RKIP expression in patients with high risk of progression UBC. Using immunohistochemistry, we determined RKIP expression levels in a series of 81 patients with high-grade pT1/pTis or muscle-invasive UBC. Staining of CD31 and D2-40 was used to assess blood and lymphatic vessels, in order to distinguish between blood and lymphatic vessel invasion (LVI). We found that 90 % of pT1/pTis tumours, 94 % of non-muscle invasive papillary tumours and 76 % of the cases without LVI occurrence expressed RKIP in >10 % of cells. In this group, we observed a subgroup of tumours (42 %) in which the tumour centre was significantly more intensely stained than the invasion front. This heterogeneous pattern was observed in 63 % of the cases with LVI. Low RKIP expression was associated with poorer 5-year disease-free and overall survival rates, and remained as an independent prognostic factor for disease-free survival. Loss of RKIP expression may be an important prognostic factor for patients with high risk of progression bladder cancer.
尿路上皮膀胱癌（UBC）是一种异质性疾病。迫切需要筛选肿瘤侵袭性的生物标志物，以便阐明 UBC 患者的临床行为并实现个体化治疗。Raf 激酶抑制蛋白（RKIP）是一种转移抑制因子，其下调与越来越多实体瘤的转移事件相关。我们评估了 RKIP 表达在高危进展性 UBC 患者中的临床和预后意义。我们使用免疫组织化学方法，在一系列 81 例高级别 pT1/pTis 或肌层浸润性 UBC 患者中测定 RKIP 的表达水平。CD31 和 D2-40 的染色用于评估血液和淋巴管，以区分血液和淋巴管浸润（LVI）。我们发现，90%的 pT1/pTis 肿瘤、94%的非肌层浸润性乳头状肿瘤和 76%的无 LVI 发生的病例中，>10%的细胞表达 RKIP。在这组患者中，我们观察到肿瘤中心比浸润前缘明显染色更深的肿瘤亚组（42%）。这种异质性模式在 63%的 LVI 病例中观察到。低 RKIP 表达与较差的 5 年无病生存率和总生存率相关，并且仍然是无病生存率的独立预后因素。RKIP 表达的丧失可能是高危进展性膀胱癌患者的一个重要预后因素。
