Department of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC; Tumor Biology Training Program, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC.
Urol Oncol. 2021 Jul;39(7):438.e1-438.e9. doi: 10.1016/j.urolonc.2021.02.007. Epub 2021 Mar 10.
Improvements to bladder cancer risk stratification guidelines are needed to better tailor post-operative surveillance and adjuvant therapy to individual patients. We previously identified STAG2 as a commonly mutated tumor suppressor gene in bladder cancer and an independent predictor of progression in NMIBC. Here we test the value of combining STAG2 immunostaining with other risk stratification biomarkers in NMIBC, and as an individual biomarker in MIBC.
STAG2 immunohistochemistry was performed on a progressor-enriched cohort of tumors from 297 patients with NMIBC, and on tumors from 406 patients with MIBC from Aarhus University Hospital in Denmark. Survival analysis was performed using Kaplan-Meier survival analysis, the log rank test, and Cox proportional hazards models.
STAG2-negative low-grade NMIBC tumors were 2.5 times less likely to progress to muscle invasion than STAG2-positive low-grade NMIBC tumors (Log-rank test, P = 0.008). In a composite group of patients with AUA intermediate and high-risk NMIBC tumors, STAG2-negative tumors were less likely to progress (Log-rank test, P = 0.02). In contrast to NMIBC, we show that STAG2 is not useful as a prognostic biomarker in MIBC.
STAG2 immunostaining can be used to subdivide low-grade NMIBC tumors into two groups with substantially different risks of disease progression. Furthermore, STAG2 immunostaining may be useful to enhance NMIBC risk stratification guidelines, though larger cohorts are needed to solidify this conclusion in individual risk groups. STAG2 is not useful as a biomarker in MIBC. Further study of the use of STAG2 immunostaining as a biomarker for predicting the clinical behavior in NMIBC is warranted.
需要改进膀胱癌风险分层指南，以便更好地根据个体患者的情况定制术后监测和辅助治疗方案。我们之前已经确定 STAG2 是膀胱癌中常见的突变肿瘤抑制基因，也是非肌层浸润性膀胱癌（NMIBC）进展的独立预测因子。在此，我们测试了将 STAG2 免疫组化与 NMIBC 中的其他风险分层生物标志物相结合的价值，并作为 MIBC 中的单个生物标志物。
对来自丹麦奥胡斯大学医院的 297 例 NMIBC 患者的进展富集队列中的肿瘤以及 406 例 MIBC 患者的肿瘤进行 STAG2 免疫组化染色。使用 Kaplan-Meier 生存分析、对数秩检验和 Cox 比例风险模型进行生存分析。
STAG2 阴性低级别 NMIBC 肿瘤进展为肌肉浸润的可能性比 STAG2 阳性低级别 NMIBC 肿瘤低 2.5 倍（对数秩检验，P=0.008）。在 AUA 中危和高危 NMIBC 肿瘤的综合患者组中，STAG2 阴性肿瘤进展的可能性较小（对数秩检验，P=0.02）。与 NMIBC 相反，我们表明 STAG2 不能作为 MIBC 的预后生物标志物。
STAG2 免疫组化可用于将低级别 NMIBC 肿瘤分为两组，两组疾病进展的风险有很大差异。此外，STAG2 免疫组化可能有助于增强 NMIBC 风险分层指南，尽管需要更大的队列来确定在各个风险组中的这一结论。STAG2 不能作为 MIBC 的生物标志物。进一步研究 STAG2 免疫组化作为预测 NMIBC 临床行为的生物标志物是值得的。
