Abstract:
There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.
摘要:
存在对能够可靠地预测BC的结果并且能够指导该疾病的管理的生物标志物的持续需要。在此设置中,我们旨在探讨转录因子P63在行根治性膀胱切除术的肌层浸润性膀胱癌(MIBC)患者中的预后价值.P63表达与临床病理特征(肿瘤分期、节点参与,固有肌层入侵的模式,乳头状结构,间生,伴随原位癌,淋巴管浸润,神经周浸润,在65例根治性膀胱切除术标本中测试了坏死)和分子亚型(基底和腔型肿瘤),并与癌症特异性生存率(CSS)和总生存率(OS)相匹配。P63阴性肿瘤显示出明显较高的固有肌层侵袭模式2的发生率(50%vs.14%,p=0.002)和变异组织学(45%vs.19%,p=0.022)与P63阳性相比。根据CK5/6和CK20的组合表达式(算法#1),P63阳性和P63阴性肿瘤大多为基底样和双阴性,分别(p=0.004)。使用算法#2,基于CK5/6和GATA3的组合表达,绝大多数肿瘤总体上和在每组中是腔内的(p=0.003)。P63阳性和P63阴性肿瘤的CSS和OS没有显著差异,但前者具有更长的操作系统趋势。尽管与具有负面预后潜力的病理特征相关,P63状态无法预测CSS和OS。那就是说,它可能有助于更好的MIBC分子分型。