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细胞周期标志物在膀胱癌评估中的应用。

Cell Cycle Markers in the Evaluation of Bladder Cancer.

机构信息

Research Laboratory of Pathology, Health Sciences Federal University of Porto Alegre (UFCSPA), 245 Sarmento Leite, Porto Alegre, RS, 90050-170, Brazil.

Departament of Urology, Santa Rita Hospital, Hospital system of the Porto Alegre Holy House of Mercy, Porto Alegre, Brazil.

出版信息

Pathol Oncol Res. 2020 Jan;26(1):175-181. doi: 10.1007/s12253-018-0389-5. Epub 2018 Mar 9.

Abstract

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

摘要

膀胱癌(BC)是一种具有高度复发性的异质性肿瘤。标准化的临床和形态学参数并不总是足以预测个体肿瘤的行为。本研究旨在评估细胞周期调节蛋白的表达,作为预测该疾病预后和监测的辅助手段。收集接受经尿道切除术(TUR)治疗的尿路上皮膀胱癌患者的石蜡块样本,进行免疫组织化学分析,检测蛋白 p16、p21、p27、p53、pRb 和 Ki-67。使用卡方检验、逻辑回归和 Kaplan-Meier 曲线分析这些标志物的预后价值。在纳入研究的 93 名患者中,主要观察到的分期类别为 T1(53%)和 Ta(29%),肿瘤分级分布为低级别患者占 58%,高级别患者占 42%。p16、p21、p27、p53、pRb 和 Ki-67 的表达分别在 31%、42%、60%、91%、27%和 56%的患者中发生改变。Ki-67 的免疫组化表达与肿瘤组织学分级相关(p=0.016),pRb 的表达与无复发生存相关(p=0.035),但在多变量分析中,没有单独的标志物与复发和进展显著相关。超过两种标志物异常表达与存在复发相关(p=0.005)和无复发生存率降低相关(p=0.004)。我们的标志物组合对 BC 具有重要的预后价值,尤其是当超过两种标志物表达异常时,预测了良好的临床复发结果。

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