Sanguedolce Francesca, Falagario Ugo Giovanni, Zanelli Magda, Palicelli Andrea, Zizzo Maurizio, Ascani Stefano, Tortorella Simona, Busetto Gian Maria, Cormio Angelo, Carrieri Giuseppe, Cormio Luigi
Pathology Unit, Policlinico Foggia, University of Foggia, 71122 Foggia, Italy.
Department of Urology and Renal Transplantation, Policlinico Foggia, University of Foggia, 71122 Foggia, Italy.
Curr Issues Mol Biol. 2024 Mar 14;46(3):2456-2467. doi: 10.3390/cimb46030155.
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%, = 0.002) and variant histology (45% vs. 19%, = 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 ( = 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 ( = 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.
一直以来都需要能够可靠预测膀胱癌预后并指导该疾病管理的生物标志物。在此背景下，我们旨在探讨转录因子P63在接受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。在65例根治性膀胱切除标本中检测了P63表达与临床病理特征（肿瘤分期、淋巴结受累情况、固有肌层浸润模式、乳头结构、间变、伴发原位癌、淋巴管浸润、神经周围浸润、坏死）以及分子亚型（基底型和腔面型肿瘤）之间的相关性，并将其与癌症特异性生存率（CSS）和总生存率（OS）进行匹配。与P63阳性肿瘤相比，P63阴性肿瘤显示出固有肌层浸润模式2（50%对14%，P = 0.002）和组织学变异（45%对19%，P = 0.022）的发生率显著更高。根据CK5/6和CK20的联合表达（算法#1），P63阳性和P63阴性肿瘤大多分别为基底样和双阴性（P = 0.004）。使用基于CK5/6和GATA3联合表达的算法#2，绝大多数肿瘤总体上以及在每组中均为腔面型（P = 0.003）。P63阳性和P63阴性肿瘤之间的CSS和OS没有显著差异，但前者有OS更长的趋势。尽管P63状态与具有负面预后潜力的病理特征相关，但它本身未能预测CSS和OS。也就是说，它可能有助于更好地对MIBC进行分子亚型分类。
