Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.
Hum Pathol. 2011 Mar;42(3):347-55. doi: 10.1016/j.humpath.2010.07.012. Epub 2010 Nov 26.
We evaluated the association of p53, p21, p27, cyclin E, and Ki-67 expression with pathologic features and clinical outcomes of patients with squamous cell carcinoma (SCC) of the urinary bladder. Immunohistochemical staining was performed on radical cystectomy specimens with pure SCC from 1997 to 2003. Bright field microscopy imaging coupled with advanced color detection software was used. The relationship between these markers and pathologic parameters as well as clinical outcome was assessed. The study included 152 patients (80.9% with bilharziasis), 99 males and 53 females, with a median age of 51 years (range, 36-74 years). The presenting stage was T2 or higher, and the presenting grade was grade II or lower in 93.4% of patients. Altered cyclin E expression was associated with stages (P = .02), altered p21 with grades (P = .02), and altered p27 with lymphovascular invasion (P = .01). In multivariable analyses, altered p53 expression was the only marker associated with an increased risk of disease recurrence (hazards ratio, 1.77; 95% confidence interval, 1.03-3.38, P = .04; and hazards ratio, 2.28; 95% confidence interval, 1.01-5.70, P = .05) and bladder cancer-specific mortality (hazards ratio, 1.76; 95% confidence interval, 1.06-2.99, P = .05, and hazards ratio, 2.64; 95% confidence interval, 1.05-5.54, P = .05) in all patients and in patients with T1-3N0 tumors, respectively. In conclusion, cell cycle-related molecular markers are commonly altered in SCC of the urinary bladder. Only p53 had a prognostic role in patients treated with radical cystectomy for SCC. Our findings support the need for further evaluation of molecular markers and their signaling pathways in SCC.
我们评估了 p53、p21、p27、细胞周期蛋白 E 和 Ki-67 的表达与膀胱癌鳞状细胞癌(SCC)患者的病理特征和临床结局之间的关系。对 1997 年至 2003 年间接受根治性膀胱切除术的单纯 SCC 膀胱切除标本进行了免疫组织化学染色。采用明场显微镜成像和先进的彩色检测软件。评估了这些标志物与病理参数和临床结局的关系。研究包括 152 例患者(80.9%有血吸虫病),99 名男性和 53 名女性,中位年龄为 51 岁(范围 36-74 岁)。患者的初始分期为 T2 或更高,初始分级为 93.4%的患者为 2 级或更低。细胞周期蛋白 E 的改变与分期有关(P=0.02),p21 的改变与分级有关(P=0.02),p27 的改变与血管淋巴管侵犯有关(P=0.01)。多变量分析显示,p53 表达改变是唯一与疾病复发风险增加相关的标志物(危险比 1.77;95%置信区间 1.03-3.38,P=0.04;危险比 2.28;95%置信区间 1.01-5.70,P=0.05),并与膀胱癌特异性死亡率相关(危险比 1.76;95%置信区间 1.06-2.99,P=0.05,危险比 2.64;95%置信区间 1.05-5.54,P=0.05),在所有患者和 T1-3N0 肿瘤患者中分别为。结论:细胞周期相关分子标志物在膀胱癌鳞状细胞癌中常发生改变。只有 p53 在接受根治性膀胱切除术治疗的 SCC 患者中具有预后作用。我们的研究结果支持进一步评估 SCC 中分子标志物及其信号通路的必要性。