Attanasio Giulio, Failla Maria, Poidomani Simone, Buzzanca Tindaro, Salzano Serena, Zizzo Maurizio, Palicelli Andrea, Zanelli Magda, Koufopoulos Nektarios, Russo Giorgio Ivan, Caltabiano Rosario, Broggi Giuseppe
Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Anatomic Pathology, University of Catania, Catania, Italy.
Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio, Emilia, Italy.
Front Oncol. 2025 Jul 15;15:1546160. doi: 10.3389/fonc.2025.1546160. eCollection 2025.
Muscle-invasive bladder cancer (MIBC) is an aggressive form of bladder cancer, representing 20-25% of all bladder cancer cases. Characterized by invasion into the detrusor muscle, MIBC often leads to high rates of metastasis and poor outcomes, with five-year survival rates below 50% for localized disease and less than 15% for metastatic cases. MIBC primarily affects older adults, especially men, with smoking and chemical exposure being the leading risk factors. Clinically, MIBC presents significant heterogeneity, both histologically and molecularly, making diagnosis and management challenging. Histological variants of MIBC, such as squamous, micropapillary, plasmacytoid, and neuroendocrine subtypes, are associated with distinct prognoses and variable treatment responses. Recent advances in genomic profiling have identified molecular subtypes of MIBC-luminal, basal/squamous, neuronal, and stroma-rich-each with unique biological characteristics and treatment sensitivities. Despite these advancements, the widespread adoption of molecular profiling is hindered by the high costs and limited availability of these technologies, particularly in resource-limited settings. As a result, there is an increasing need for alternative, more accessible diagnostic methods to predict molecular subtypes. In this context, histological examination combined with immunohistochemical markers, such as GATA3, KRT5/6, and p63, has been shown to reliably correlate with molecular subtypes and guide therapeutic decisions. This review presents a comprehensive analysis of how histology, immunohistochemistry and molecular subtyping can be integrated into routine clinical practice to inform treatment strategies for MIBC, providing a pathway toward more personalized and effective management.
肌层浸润性膀胱癌（MIBC）是一种侵袭性膀胱癌，占所有膀胱癌病例的20%-25%。MIBC的特征是侵犯逼尿肌，常导致高转移率和不良预后，局部疾病的五年生存率低于50%，转移病例的五年生存率低于15%。MIBC主要影响老年人，尤其是男性，吸烟和接触化学物质是主要危险因素。临床上，MIBC在组织学和分子水平上均表现出显著的异质性，这使得诊断和管理具有挑战性。MIBC的组织学变体，如鳞状、微乳头、浆细胞样和神经内分泌亚型，与不同的预后和可变的治疗反应相关。基因组分析的最新进展已经确定了MIBC的分子亚型——腔面型、基底/鳞状型、神经元型和富含基质型——每种亚型都具有独特的生物学特征和治疗敏感性。尽管有这些进展，但这些技术的高成本和有限的可及性阻碍了分子分析的广泛应用，特别是在资源有限的环境中。因此，越来越需要替代的、更易获得的诊断方法来预测分子亚型。在这种背景下，组织学检查结合免疫组化标记物，如GATA3、KRT5/6和p63，已被证明与分子亚型可靠相关，并可指导治疗决策。本综述全面分析了如何将组织学、免疫组化和分子亚型分析整合到常规临床实践中，为MIBC的治疗策略提供依据，为更个性化和有效的管理提供途径。
