Prognostic influence of microsatellite alterations of muscle-invasive bladder cancer treated with radical cystectomy,Urologic Oncology: Seminars and Original Investigations

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Prognostic influence of microsatellite alterations of muscle-invasive bladder cancer treated with radical cystectomy
Urologic Oncology: Seminars and Original Investigations ( IF 2.4 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.urolonc.2021.08.020
Amira Awadalla ₁ , Ahmed M Harraz ₂ , Hassan Abol-Enein ₃ , Mahmoud Laymon ₂ , Asmaa E Ahmed ₁ , Mona Abdel-Rahim ₁ , Abdel-Rahman N Zekri ₄ , Ahmed A Shokeir ₃

Affiliation

Objective

To examine the prognostic effect of microsatellite instability (MSI) and loss of heterozygosity (LOH) on cancer-specific survival (CSS) in patients with muscle-invasive bladder cancer (MIBC).

Patients and methods

The liquid nitrogen-preserved specimens of 220 patients between March 2009 and December 2012 were analyzed for the presence of MSI and LOH in 12 loci (ACTBP2, D16S310, D16S476, D18S51, D4S243, D9S162, D9S171, D9S747, FGA, INF-α, MBP, MJD) using polymerase chain reaction. MSI was defined as MSI-stable, MSI-Low, or MSI-High if instability was detected in 0, 1, or 2 or more of the examined markers, respectively. The association between MSI-High and LOH and CSS was analyzed using uni- and multivariate analyses and the degree of agreement between tumor and urine samples were determined.

Results

MSI were found in 1030 (39%) and 1148 (43.5%) in tumor and urine specimens, respectively (Kappa = 0.77). On the other hand, LOH was found in 163 (6.2%) of tumor tissues and 44 (1.7%) in urine specimens (Kappa = 0.34). Microsatellite alterations were significantly associated with worse CSS at 1- and 5-year in tumor tissue (95% and 83.7% vs. 65.8% and 3.5%, respectively; P < 0.001) and in urine sample (90% and 64% vs. 46.5% and 9.3%, respectively; P < 0.001). MSI and/or LOH was an independent predictor of CSS (HR: 9.8; 95%CI: 5.1–18.9; P < 0.001).

Conclusions

Microsatellite alterations were potentially an independent predictor of CSS in patients with MIBC. The agreement was good between tumor and urine MSI but weak for LOH.

中文翻译：

根治性膀胱切除术治疗肌肉浸润性膀胱癌的微卫星改变对预后的影响

客观的

研究微卫星不稳定性 (MSI) 和杂合性缺失 (LOH) 对肌肉浸润性膀胱癌 (MIBC) 患者癌症特异性生存期 (CSS) 的预后影响。

患者和方法

对 2009 年 3 月至 2012 年 12 月间 220 名患者的液氮保存标本进行了 12 个位点（ACTBP2、D16S310、D16S476、D18S51、D4S243、D9S162、D9S171、D9S747、FGA、INF-α、 MBP, MJD) 使用聚合酶链式反应。如果分别在 0、1 或 2 个或更多检查标记中检测到不稳定性，则将 MSI 定义为 MSI-stable、MSI-Low 或 MSI-High。使用单变量和多变量分析分析 MSI-High 与 LOH 和 CSS 之间的关联，并确定肿瘤和尿液样本之间的一致性程度。

结果

MSI 分别在 1030 (39%) 和 1148 (43.5%) 的肿瘤和尿液样本中发现 ( Kappa  = 0.77)。另一方面，在 163 个（6.2%）的肿瘤组织和 44 个（1.7%）的尿液样本中发现了 LOH（Kappa  = 0.34）。微卫星改变与肿瘤组织（分别为 95% 和 83.7% 对 65.8% 和 3.5%；P < 0.001）和尿液样本（90% 和 64% 对分别为 46.5% 和 9.3%；P < 0.001)。MSI 和/或 LOH 是 CSS 的独立预测因子（HR：9.8；95%CI：5.1-18.9；P < 0.001）。