Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia.
Tumor Biology Training Program, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia.
Clin Cancer Res. 2018 Sep 1;24(17):4145-4153. doi: 10.1158/1078-0432.CCR-17-3244. Epub 2018 Jun 28.
Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot cohort that -mutant tumors recurred less frequently than wild-type tumors. Here, we report a STAG2 biomarker validation study using two independent cohorts of clinically annotated papillary NMIBC tumors from the United States and Europe. The value of STAG2 immunostaining for prediction of recurrence was initially evaluated in a cohort of 82 patients with papillary NMIBC ("Georgetown cohort"). Next, the value of STAG2 immunostaining for prediction of progression to muscle invasion was evaluated in a progressor-enriched cohort of 253 patients with papillary NMIBC ("Aarhus cohort"). In the Georgetown cohort, 52% of NMIBC tumors with intact STAG2 expression recurred, whereas 25% of STAG2-deficient tumors recurred ( = 0.02). Multivariable analysis identified intact expression as an independent predictor of recurrence (HR = 2.4; = 0.05). In the progressor-enriched Aarhus cohort, 38% of tumors with intact STAG2 expression progressed within 5 years, versus 16% of STAG2-deficient tumors ( < 0.01). Multivariable analysis identified intact STAG2 expression as an independent predictor of progression (HR = 1.86; = 0.05). STAG2 IHC is a simple, binary, new assay for risk stratification in papillary NMIBC. .
大多数膀胱癌是早期肿瘤，称为乳头状非肌肉浸润性膀胱癌（NMIBC）。切除后，多达 70%的 NMIBC 会局部复发，其中多达 20%的复发会进展为肌肉浸润。目前需要额外的生物标志物来根据肿瘤的复发和进展风险对其进行分层。我们之前发现 是 NMIBC 中最常突变的基因之一，并在一个试点队列中提供了初步证据，表明 -突变肿瘤的复发频率低于 野生型肿瘤。在这里，我们报告了一项使用来自美国和欧洲的两个独立的临床注释的乳头状 NMIBC 肿瘤队列的 STAG2 生物标志物验证研究。首先在一个 82 例乳头状 NMIBC 患者的队列（“乔治城队列”）中评估了 STAG2 免疫染色对预测复发的价值。接下来，在一个包含 253 例乳头状 NMIBC 的进展富集队列（“奥胡斯队列”）中评估了 STAG2 免疫染色对预测进展为肌肉浸润的价值。在乔治城队列中，52%的 STAG2 表达完整的 NMIBC 肿瘤复发，而 25%的 STAG2 缺陷肿瘤复发（= 0.02）。多变量分析确定完整的 表达是复发的独立预测因子（HR = 2.4；= 0.05）。在进展富集的奥胡斯队列中，5 年内有完整 STAG2 表达的肿瘤中，有 38%进展，而 STAG2 缺陷的肿瘤中，有 16%进展（< 0.01）。多变量分析确定完整的 STAG2 表达是进展的独立预测因子（HR = 1.86；= 0.05）。STAG2 IHC 是一种简单的、二分类的新检测方法，用于预测乳头状 NMIBC 的风险分层。
