Department of Pathology, Stavanger University Hospital, 4068 Stavanger, Norway; Clinical Institute-1, Medical Odontology Faculty, University in Bergen, 5020 Bergen, Norway.
Department of Pathology, Stavanger University Hospital, 4068 Stavanger, Norway.
Hum Pathol. 2014 Jul;45(7):1496-503. doi: 10.1016/j.humpath.2014.03.001. Epub 2014 Mar 26.
European treatment guidelines of non-muscle-invasive urothelial carcinoma of the urinary bladder are strongly dependent on grade, but grading reproducibility is wanting. Protocolized proliferation features such as Mitotic Activity Index (MAI), Ki-67, and phosphohistone H3 are prognostic and reproducible. The objective of this population-based study was to compare proliferation biomarkers with each other and with World Health Organization (WHO) 1973/2004 grades with regard to prediction of stage progression. A total of 193 primary non-muscle-invasive urothelial carcinomas were analyzed using WHO73/04 grades and measurement of the proliferation markers mentioned above. Sensitivities, specificities, and positive and negative predictive values with confidence intervals (CIs) were estimated with regard to progression prediction. Kaplan-Meier survival curves were made, and the hazard ratio and Harrell's C-index with 95% CIs, P values, and adjusted C-index for stage progression or not of WHO73, WHO04, and the proliferation markers were calculated. The median follow-up time was 75 months (range, 1-127). A total of 111 patients (52%) experienced recurrence within 5 years, and 14 patients (7%) progressed. High values of MAI predicted stage progression with a positive predictive value of 0.22 (95% CI, 0.12-0.37). The positive predictive value of Ki-67 and phosphohistone H3 were 0.15 (both 95% CIs, 0.07-0.29) and comparable to that of the WHO04. The prognostic value of MAI was strongest, exceeding that of the other proliferation markers and the WHO grading systems. In conclusion, in non-muscle-invasive urinary bladder urothelial carcinomas, proliferation biomarkers have prognostic value, possibly exceeding that of the WHO classifications.
欧洲非肌肉浸润性膀胱尿路上皮癌的治疗指南强烈依赖于分级，但分级的可重复性存在问题。有丝分裂活性指数（MAI）、Ki-67 和磷酸组蛋白 H3 等程序性增殖特征具有预后和可重复性。本基于人群的研究目的是比较增殖生物标志物彼此之间以及与世界卫生组织（WHO）1973/2004 分级在预测分期进展方面的差异。共分析了 193 例原发性非肌肉浸润性膀胱尿路上皮癌，采用 WHO73/04 分级和上述增殖标志物的测量。估计了进展预测方面的敏感性、特异性、阳性和阴性预测值及其置信区间（CI）。制作 Kaplan-Meier 生存曲线，并计算了危险比和 Harrell's C 指数及其 95%CI、P 值以及针对 WHO73、WHO04 和增殖标志物的调整 C 指数，以评估分期进展或不进展的情况。中位随访时间为 75 个月（范围，1-127）。共有 111 例患者（52%）在 5 年内复发，14 例患者（7%）进展。MAI 值高预测分期进展，阳性预测值为 0.22（95%CI，0.12-0.37）。Ki-67 和磷酸组蛋白 H3 的阳性预测值分别为 0.15（95%CI，0.07-0.29），与 WHO04 相当。MAI 的预后价值最强，超过了其他增殖标志物和 WHO 分级系统。总之，在非肌肉浸润性膀胱尿路上皮癌中，增殖生物标志物具有预后价值，可能超过 WHO 分类。
