Breyer Johannes, Shalekenov Sanzhar, Aziz Atiqullah, van Rhijn Bastiaan W G, Bründl Johannes, Lausenmeyer Eva, Schäfer Julius, Denzinger Stefan, Giedl Christian, Burger Maximilian, Hartmann Arndt, Evert Matthias, Otto Wolfgang
Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany.
Department of Urology, University of Hamburg, Hamburg, Germany.
Bladder Cancer. 2017 Jul 27;3(3):173-180. doi: 10.3233/BLC-170103.
To investigate the predictive impact of the proliferation biomarker Ki-67 on the clinical course of patients with initial stage pTa urothelial carcinoma of the bladder (UCB).
We retrospectively analyzed all patients treated by transurethral resection of bladder tumors (TUR-B) for UCB between 1992-2004 in a single-center. Disease recurrence (≥pTa UCB) and absent tumor in histopathology, assessed by TUR-B with a non-malignant result for endoscopic suspect bladder lesion displayed endpoints. Immunohistochemical (IHC) analysis of formalin-fixed and paraffin-embedded tissue blocks was performed with an immunostainer using a primary antibody for Ki-67. Semiquantitative evaluation of Ki-67 was performed by three reviewers. Increased proliferation was defined with a cut-off value of ≥50%. Uni- and multivariable binary regression analyses were applied to address prediction of disease recurrence.
215 patients (84% male, median age 69 years at first diagnosis) were evaluable and included to the study. 89 patients stayed disease-free (41%), 126 patients showed recurrence (59%). Recurrence rates of patients with Ki-67 expression <10%, 10-24%, 25-49% and ≥50% were 14.8% vs. 30.8% vs. 63.9% and 80.7%, respectively ( < 0.001). In Kaplan-Meier analysis patients with increased proliferation ≥50% showed a statistically significant worse 10-year recurrence-free survival (19% vs. 57%, < 0.001). Multivariable regression analysis revealed instillation treatment ( = 0.001) and high proliferation of Ki-67 ( < 0.001) to be independent predictors of recurrence in stage pTa UCB.
High proliferation with Ki-67 expression ≥50% was strongly associated with worse recurrence-free survival in patients with initial stage pTa UCB. Stage pTa UCB patients with increased Ki-67 expression should undergo a strictly follow-up regime comparable to stage pT1 bladder carcinoma, while at least patients with Ki-67 expression <10% might be feasible for more liberate follow-up regime after evaluation of our data in randomized, prospective and multicenter studies.
探讨增殖生物标志物Ki-67对膀胱pTa期尿路上皮癌（UCB）患者临床病程的预测影响。
我们回顾性分析了1992年至2004年间在单中心接受经尿道膀胱肿瘤切除术（TUR-B）治疗UCB的所有患者。以疾病复发（≥pTa UCB）和组织病理学无肿瘤为终点，通过TUR-B对内镜可疑膀胱病变进行评估，其结果为非恶性。使用针对Ki-67的一抗，通过免疫染色仪对福尔马林固定、石蜡包埋的组织块进行免疫组织化学（IHC）分析。由三位审阅者对Ki-67进行半定量评估。增殖增加定义为截断值≥50%。应用单变量和多变量二元回归分析来预测疾病复发。
215例患者（84%为男性，首次诊断时中位年龄69岁）可评估并纳入研究。89例患者无疾病复发（41%），126例患者出现复发（59%）。Ki-67表达<10%、10 - 24%、25 - 49%和≥50%的患者复发率分别为14.8%、30.8%、63.9%和80.7%（<0.001）。在Kaplan-Meier分析中，增殖增加≥50%的患者10年无复发生存率在统计学上显著更差（19%对57%，<0.001）。多变量回归分析显示膀胱灌注治疗（=0.001）和Ki-67高增殖（<0.001）是pTa期UCB复发的独立预测因素。
Ki-67表达≥50%的高增殖与pTa期UCB患者较差的无复发生存率密切相关。Ki-67表达增加的pTa期UCB患者应接受与pT1期膀胱癌相当的严格随访方案，而至少Ki-67表达<10%的患者在随机、前瞻性和多中心研究中评估我们的数据后，可能适合更宽松的随访方案。
