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Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer

Nat Rev Urol. 2014 Jul;11(7):400-10

Nat Rev Urol. 2014 Jul;11(7):400-10.


Whole-genome analyses have revealed that muscle-invasive bladder cancers (MIBCs) are heterogeneous and can be grouped into basal and luminal subtypes that are highly reminiscent of those found in breast cancer. Basal MIBCs are enriched with squamous and sarcomatoid features and are associated with advanced stage and metastatic disease at presentation. Like basal breast cancers, basal bladder tumours contain a claudin-low subtype that is enriched with biomarkers characteristic of epithelial-to-mesenchymal transition. The stem cell transcription factor ΔNp63α controls basal MIBC gene expression, just as it does in basal breast cancers. Luminal MIBCs are enriched with activating FGFR3 and ERBB3 mutations and ERBB2 amplifications, and their gene expression profiles are controlled by peroxisome proliferator activator receptor γ (PPARγ) and possibly also by oestrogen receptor activation. Luminal bladder cancers can be further subdivided into two subtypes, p53-like and luminal, which can be distinguished from one another by different levels of biomarkers that are characteristic of stromal infiltration, cell cycle progression, and proliferation. Importantly, basal bladder cancers are intrinsically aggressive, but are highly sensitive to cisplatin-based combination chemotherapy. Although the luminal subtypes are not as intrinsically aggressive as basal cancers, p53-like tumours are resistant to chemotherapy and might, therefore, represent a problem for treated patients.

Comment from Maria Ribal: The use of neoadjuvant chemotherapy is increasing lately, in response to the data- clearly demonstrating its impact on survival in patients with bladder cancer.
Although some clinical features may indicate the best candidates for this treatment, even response markers are needed to achieve a more efficient use. Nowadays we are living the period where whole genome of tumors are going to be implemented. This would change the view of solid tumors. Recently the presence of different cell subtypes in bladder cancer has been demonstrated. This fact could open the door to new concepts on chemo-resistance.