Department of Surgery, Division of Urology, American University of Beirut Medical Center, Beirut, Lebanon.
Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon.
Cancer Rep (Hoboken). 2021 Apr;4(2):e1313. doi: 10.1002/cnr2.1313. Epub 2021 Feb 4.
Bladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle-invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low-cost technique to predict prognosis in bladder cancer patients in our region.
To examine the feasibility of low-cost triple-marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity.
We collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut-off of ≥20% was set as positive. Kaplan-Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype. We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double-positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09-0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS.
Specimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple-marker IHC could serve as a potential low-cost prognostic indicator to identify patients at high risk of progression.
膀胱癌是全球第九大常见癌症，也是黎巴嫩的第三大常见癌症。免疫组织化学（IHC）已被用于将肌层浸润性膀胱癌（MIBC）分为不同亚型。然而，据我们所知，在我们所在地区，尚无研究调查使用这种低成本技术来预测膀胱癌患者的预后。
检验低成本三标志物 IHC 评估 MIBC 亚型在预测患者生存和顺铂敏感性方面的可行性。
我们收集了我院病理诊断为 MIBC 的已故患者的标本。对每个病例，均从肿瘤组织块中提取组织，并进行苏木精和伊红染色，同时通过 IHC 对三种分子标志物进行染色：细胞角蛋白 5/6、细胞角蛋白 14 染色基底 BC 和 GATA3 染色腔面 BC。将≥20%设定为阳性。通过 BC 亚型构建 Kaplan-Meier 曲线，预测总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFS）。还使用 Cox 回归创建了考虑肿瘤因素和 BC 亚型的危险比。我们将标本分为腔面（仅 GATA3 阳性）（n = 21；56.7%）或双阳性（GATA3 和基底细胞角蛋白 5/6 或细胞角蛋白 14 阳性）（n = 16；43.3%）。两种类型的总体中位生存期相似（27.0±4.82 个月）。PFS 方面，腔面疾病的数值更高（Breslow P =.032）。调整协变量后，腔面分子表达预测 PFS（0.28；[0.09-0.94]）。然而，Cox 模型无法识别 OS 或 DSS 的任何预测因素。
仅富含腔面分子谱的标本更有可能表现出顺铂敏感性。尽管目前没有指南建议在临床实践中使用分子谱分析，但三标志物 IHC 可作为一种潜在的低成本预后指标，用于识别有进展高风险的患者。
