Department of Urology, Weill Cornell Medical College, New York, NY10065, USA; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Urol Oncol. 2013 Nov;31(8):1716-24. doi: 10.1016/j.urolonc.2012.06.011. Epub 2012 Sep 1.
We assessed the association of serine protease inhibitor Kazal type I (SPINK1) expression with clinicopathologic outcomes in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC).
Tissue microarrays comprising 438 consecutive UCB patients treated with RC between 1988 and 2003 and 62 cases of normal urothelium controls were evaluated for SPINK1 protein expression by immunohistochemistry (IHC). Semiquantitative evaluation was performed by 2 pathologists blinded to clinical outcomes (loss of expression: <50% cells or intensity 0-2).
In normal urothelium, SPINK1 expression was noted in umbrella cells of 32 of 62 controls (52%); 254 RC patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with higher pathologic stages (P = 0.002) and presence of lymph node metastasis (P = 0.04). At a median follow-up of 130 months (IQR: 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (P = 0.02) and cancer-specific mortality (P = 0.03). On multivariable analysis that adjusted for the effects of standard clinicopathologic parameters, SPINK1 was not an independent predictor of disease recurrence (P = 0.09) or cancer-specific mortality (P = 0.12).
Over half of UCB patients treated with RC exhibit loss of SPINK1 expression. Loss of SPINK1 correlates with features of biologically aggressive UCB. Although SPINK1 expression did not have independent prognostic value in RC patients, it may serve as a biomarker for tumor staging and may be useful as an adjunct in clinical decision-making.
我们评估了丝氨酸蛋白酶抑制剂 Kazal 型 I（SPINK1）表达与接受根治性膀胱切除术（RC）治疗的膀胱癌（UCB）患者临床病理结局的关系。
使用组织微阵列，评估了 1988 年至 2003 年间接受 RC 治疗的 438 例连续 UCB 患者和 62 例正常尿路上皮对照的 SPINK1 蛋白表达情况，采用免疫组织化学（IHC）进行检测。由 2 位对临床结果不知情的病理学家进行半定量评估（表达缺失：<50%的细胞或强度 0-2）。
在正常尿路上皮中，62 例对照中有 32 例（52%）观察到 SPINK1 表达；254 例 RC 患者（57.9%）表现出 SPINK1 表达缺失。SPINK1 表达缺失与较高的病理分期（P=0.002）和淋巴结转移的存在显著相关（P=0.04）。在中位随访 130 个月（IQR：98.4）时，SPINK1 表达缺失与疾病复发风险增加（P=0.02）和癌症特异性死亡率（P=0.03）相关。在调整标准临床病理参数影响的多变量分析中，SPINK1 不是疾病复发（P=0.09）或癌症特异性死亡率（P=0.12）的独立预测因子。
超过一半接受 RC 治疗的 UCB 患者表现出 SPINK1 表达缺失。SPINK1 缺失与生物学侵袭性 UCB 的特征相关。尽管 SPINK1 表达在 RC 患者中没有独立的预后价值，但它可能作为肿瘤分期的生物标志物，并可能有助于临床决策。
