Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer

Abstract

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.

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

“…Actually, gene expression studies have identified different intrinsic subtypes of MIBC such as basal and luminal ones, similar to those found in breast cancer [69]. Basal BC seems to be intrinsically aggressive and associated with advanced stage and metastases at diagnosis and, therefore, with worse survival outcomes compared with the luminal subtype [70]. Surprisingly, HER2 overexpression is a well-known characteristic feature of luminal BC [10,71].…”

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

“…It is almost never associated with human papillomavirus infection, with the rare exception of some cases with a basaloid morphology [67,68]. Interestingly, recent genomic data have described a basal/squamous-like molecular subtype that has squamoid morphology and immunophenotype and is associated with poor survival and poor response to systemic therapy [69,70]. Glandular neoplasms constitute the second most common form of divergent differentiation, seen in up to 18% of invasive tumours and defined by the presence of gland formation [71][72][73].…”

Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis

“…Although essentially unaddressed in lung cancer, a claudin-low phenotype has been linked to EMT, stemness, and chemotherapy resistance in breast and bladder cancer (36)(37)(38). CLDN7 is known to inhibit human lung cancer invasion (15), and low expression of CLDN7 is linked to poor prognosis in NSCLC (39).…”