Department of Urology, University of California-Los Angeles, Los Angeles, California 90095-1738, USA.
J Urol. 2010 Jun;183(6):2403-8. doi: 10.1016/j.juro.2010.01.064. Epub 2010 Apr 18.
CD44v6 is a cell surface protein involved in cell migration, cell adhesion, tumor progression and metastatic spread. We evaluated its role as a molecular marker for urothelial bladder cancer.
A tissue microarray was constructed containing 410 primary urothelial bladder cancers, each in triplicate. Immunohistochemical staining was done with a commercially available antibody. The percent of tumor cells staining positive for CD44v6 was evaluated and we assessed associations with stage, grade and survival.
CD44v6 expression was higher in noninvasive (Ta, Tis) vs invasive (T1-T4) tumors (p <0.001). It decreased with increasing grade (p <0.001). In patients who underwent transurethral bladder resection absent CD44v6 expression was associated with a 2.3-fold increased risk of recurrence (95% CI 1.28 to 4.08). Median time to recurrence for tumors with vs without CD44v6 expression was 23 vs 9 months (p = 0.003). In a multivariate Cox model absent CD44 expression was an independent adverse prognostic factor for tumor recurrence (HR 2.33, p = 0.006). In cystectomy cases median overall survival for CD44v6 nonexpression vs expression was 30 vs 75 months (p = 0.0027) and CD44v6 expression was retained as an independent prognostic factor for overall survival (HR 1.54, p = 0.042).
Absent CD44v6 expression is an independent adverse predictor of urothelial bladder cancer recurrence and overall survival. Routine evaluation of CD44v6 expression may allow the identification of high risk patients who require more intensive surveillance or aggressive therapy. Targeting of CD44v6 with monoclonal antibodies may provide new avenues for urothelial bladder cancer imaging and treatment.
CD44v6 是一种细胞表面蛋白，参与细胞迁移、细胞黏附、肿瘤进展和转移扩散。我们评估了其作为尿路上皮膀胱癌分子标志物的作用。
构建了一个组织微阵列，包含 410 例原发性尿路上皮膀胱癌，每个标本均重复 3 次。使用商业可得的抗体进行免疫组织化学染色。评估 CD44v6 阳性肿瘤细胞的比例，并评估其与分期、分级和生存的相关性。
CD44v6 表达在非浸润性（Ta、Tis）与浸润性（T1-T4）肿瘤之间更高（p<0.001）。随着分级的增加而降低（p<0.001）。在接受经尿道膀胱切除术的患者中，CD44v6 表达缺失与复发风险增加 2.3 倍相关（95%CI 1.28 至 4.08）。有 CD44v6 表达与无 CD44v6 表达的肿瘤复发中位时间分别为 23 个月和 9 个月（p=0.003）。在多变量 Cox 模型中，CD44 表达缺失是肿瘤复发的独立不良预后因素（HR 2.33，p=0.006）。在膀胱切除术病例中，CD44v6 无表达与表达的总生存中位数分别为 30 个月和 75 个月（p=0.0027），并且 CD44v6 表达仍然是总生存的独立预后因素（HR 1.54，p=0.042）。
CD44v6 表达缺失是尿路上皮膀胱癌复发和总生存的独立不良预测因素。常规评估 CD44v6 表达可能有助于识别需要更密集监测或更积极治疗的高危患者。用单克隆抗体靶向 CD44v6 可能为尿路上皮膀胱癌的成像和治疗提供新途径。
