Squamous differentiation in pT1 bladder urothelial carcinoma predicts poor response for intravesical chemotherapy

Li, Gang; Hu, Jielun; Niu, Yuanjie

doi:10.18632/oncotarget.18563

Cited by 12 publications

(14 citation statements)

References 21 publications

(23 reference statements)

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“…Accordingly, a scarce response to BCG therapy has been reported by Gofrit et al [54], with lower 5-year survival rates compared to patients with pure HG UC (79.1 vs. 89.5%, respectively). In keeping with this, the presence of a squamous component was associated with a poorer prognosis than GD in T1-HG NMIBC conservatively treated with intravesical chemotherapy (mitomycin C, Adriamycin, pirarubicin) and BCG [76], and was a prognostic factor for recurrence and progression in a large series of 213 T1 NMIBC managed cases with intravesical chemotherapy (epirubicin or hydroxycamptothecin) [96].…”

Section: Squamous Differentiationsupporting

confidence: 55%

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

et al. 2021

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Background: The most common bladder cancer (BC) histotype is pure urothelial carcinoma (UC), which may undergo divergent differentiation in some cases. Variant histology (VH) presents along variable morphologies, either single or combined between them or with pure UC. From a clinical standpoint, the vast majority of BC is diagnosed at non-invasive or minimally invasive stages, namely as non-muscle invasive BC (NMIBC). There is a wide range of therapeutic options for patients with NMIBC, according to their clinical and pathological features. However, current risk stratification models do not show optimal effectiveness. Evidence from the literature suggests that VH has peculiar biological features, and may be associated with poorer survival outcomes compared to pure UC. Summary: In order to describe the biological features and prognostic/predictive role of VH in NMIBC, and to discuss current treatment options, we performed a systematic literature search through multiple databases (PubMed/Medline, Google Scholar) for relevant articles according to the following terms, single and/or in combination: “non-muscle invasive bladder cancer,” “variant histology,” “micropapillary variant,” “glandular differentiation,” “squamous differentiation,” “nested variant,” “plasmacytoid variant,” and “sarcomatoid variant.” We extracted 99 studies including original articles, reviews, and systematic reviews, and subsequently analyzed data from 16 studies reporting on the outcome of NMIBC with VH. We found that the relative rarity of these forms as well as the heterogeneity in study populations and therapeutic protocols results in conflicting findings overall. Key Messages: The presence of VH should be taken into account when counseling a patient with NMIBC, since it may upgrade the disease to high-risk tumor and thus warrant a more aggressive treatment.

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Section: Squamous Differentiationsupporting

confidence: 55%

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

et al. 2021

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“…Low‐grade urothelial carcinoma with focal squamous differentiation has a higher recurrence rate than pure low‐grade urothelial carcinoma . Tumours with any identifiable urothelial element are classified as urothelial carcinoma with squamous differentiation, and an estimate of the percentage of squamous component should be provided in the report.…”

Section: Urothelial Carcinoma With Divergent Differentiationmentioning

confidence: 99%

“…[14][15][16][17][18][19][20]25 Low-grade urothelial carcinoma with focal squamous differentiation has a higher recurrence rate than pure low-grade urothelial carcinoma. 23,26 Tumours with any identifiable urothelial element are classified as urothelial carcinoma with squamous differentiation, and an estimate of the percentage of squamous component should be provided in the report. Urothelial carcinoma with squamous differentiation may express urothelial (S100P, 83%; GATA3, 35%; uroplakin II, 13%) and squamous associated markers (CK14, 87%; desmoglein-3, 70%).…”

Section: U R O T H E L I a L C A R C I N O M A W I T H S Q U A M O U mentioning

confidence: 99%

Variants and new entities of bladder cancer

et al. 2018

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Pathological evaluation of bladder cancer typically reveals great tumour heterogeneity, and therefore the common observation of urothelial carcinoma exhibiting a wide variety of histopathological patterns is not surprising. Some of these patterns are so distinctive that they have been recognised as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organisation (WHO) classification of tumours of the urinary system and male genital organs. The current WHO classifications clarify terminological issues and provide better definition criteria, but also incorporate some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily pathology practice. This review will discuss the features of variants of urothelial carcinoma in the context of our current clinical practice. Histological variations and new entities of bladder cancer not included in the current WHO classification of urothelial tumours will be briefly discussed.

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“…Still, bladder cancer is the most frequent urogenital malignant tumor concerning both sexes worldwide with estimated ~549,400 new cases and 200,000 deaths [ 25 ]. Histologically, bladder cancer comprises a heterogeneous spectrum including urothelial cancers with squamous differentiation, which have been associated with poor response to chemotherapy [ 26 , 27 ]. Since urothelial cancers have been further classified into distinct molecular subtypes [ 28 , 29 ] confirming a basal-type with squamous features (BASQ) associated with poor prognosis [ 30 ], we aimed to give additional insights into ITIH5 expression and its functional and therapeutic implications for this clinically important subgroup.…”

Section: Introductionmentioning

confidence: 99%

The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder Cancer Cells

Rose

Noetzel

Kistermann

et al. 2021

Cells

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This study aims at characterizing the role of the putative tumor suppressor ITIH5 in basal-type bladder cancers (BLCA). By sub-classifying TCGA BLCA data, we revealed predominant loss of ITIH5 expression in the basal/squamous-like (BASQ) subtype. ITIH5 expression inversely correlated with basal-type makers such as KRT6A and CD44. Interestingly, Kaplan–Meier analyses showed longer recurrence-free survival in combination with strong CD44 expression, which is thought to mediate ITIH-hyaluronan (HA) binding functions. In vitro, stable ITIH5 overexpression in two basal-type BLCA cell lines showing differential CD44 expression levels, i.e., with (SCaBER) and without squamous features (HT1376), demonstrated clear inhibition of cell and colony growth of BASQ-type SCaBER cells. ITIH5 further enhanced HA-associated cell-matrix attachment, indicated by altered size and number of focal adhesion sites resulting in reduced cell migration capacities. Transcriptomic analyses revealed enrichment of pathways and processes involved in ECM organization, differentiation and cell signaling. Finally, we provide evidence that ITIH5 increase sensitivity of SCaBER cells to chemotherapeutical agents (cisplatin and gemcitabine), whereas responsiveness of HT1376 cells was not affected by ITIH5 expression. Thus, we gain further insights into the putative role of ITIH5 as tumor suppressor highlighting an impact on drug response potentially via the HA-CD44 axis in BASQ-type BLCA.

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Squamous differentiation in pT1 bladder urothelial carcinoma predicts poor response for intravesical chemotherapy

Cited by 12 publications

References 21 publications

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

Variants and new entities of bladder cancer

The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder Cancer Cells

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