Urothelial Carcinoma Stem Cells: Current Concepts, Controversies, and Methods

Carcinosarcoma of the upper urinary tract is very rare. In this article, we report a case of upper urinary tract carcinosarcoma with rhabdomyoblastic differentiation showing distinct transition between the epithelial and mesenchymal components confirmed by morphology and immunohistochemistry. An 81-year-old female underwent radical nephroureterectomy under the diagnosis of left ureteral urothelial carcinoma (UC). Multiple invasive tumors showed combined histology with UC and rhabdomyosarcomatous elements (pT2-ureter and pT3-renal pelvis, pN0, u-lt0, ly0, v0, RM0). Each element demonstrated typical epithelial or mesenchymal staining patterns (positive for AE1/AE3 in the former and positive for vimentin and myogenin in the latter). Notably, immunohistochemical transition patterns of GATA-3, p63, SOX2, and myogenin between UC and rhabdomyosarcomatous elements were observed, implying possible involvement of neoplastic stem cells in the process of carcinosarcoma formation. The patient did not receive any adjuvant therapy and eventually succumbed to multiple visceral metastases (lungs and liver) at 11 months postoperatively. No autopsy was performed.

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Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-015-0259-x ◽

2015 ◽

Vol 34 (1) ◽

Cited By ~ 16

Author(s):

Margaretha A. Skowron ◽

Günter Niegisch ◽

Gerhard Fritz ◽

Tanja Arent ◽

Joep G. H. van Roermund ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Urothelial Carcinoma ◽

Cell Lines ◽

Cisplatin Resistance ◽

Carcinoma Cell ◽

Carcinoma Cell Lines ◽

Phenotype Plasticity ◽

Urothelial Carcinoma Cell

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Molecular determinants of recurrences of the human urothelial tumor

Cancer Urology ◽

10.17650/1726-9776-2021-17-3-130-139 ◽

2021 ◽

Vol 17 (3) ◽

pp. 130-139

Author(s):

V. Yu. Startsev ◽

A. E. Balashov ◽

A. S. Merzlyakov ◽

S. L. Vorobiov ◽

E. S. Kozorezova

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Urothelial Carcinoma ◽

Expression Profiles ◽

Transitional Cell ◽

Disease Free Survival ◽

Circulating Tumor Dna ◽

Clinical Diagnostics ◽

Tumor Focus ◽

Tumor Dna

Background. Urothelial carcinoma (UTC) is an aggressive disease with a known propensity for frequent recurrence. It is difficult to predict the velocity of the development of UTC recur using modern means of clinical diagnostics. Therefore, the development of the capabilities of histo-morphological study of tumor tissues is of particular relevance.Materials and methods. The materials of publications (PubMed, CrossRef) for 1990-2021, devoted to the choice of biomarkers for the diagnosis of UTC, the analysis of molecular pathways, progression and metastasis, were studied. The search was carried out for the key phrases "urothelial carcinoma", "recurrent UTK", "stem cells", "biomarkers of bladder cancer", "genetic changes in urothelium", "circulating tumor DNA".Results. Cancer stem cells serve as a source of UTC recurrence after removal from the primary focus, localizing in any areas of the urothelium, as well as outside the main tumor focus and are characterized by a common genotype, but different phenotypic manifestations. To predict the recurrence of the tumour is advisable to use gene expression signatures, since the subtypes of UTC are characterized by clear gene expression profiles. A larger sample and independent dataset is needed to confirm the clinical significance of the findings. Combined biomarkers predict UTC behavior, and FGFR3 and TP53 mutations can be components for a panel for predicting UTC recurrence. The use of the liquid biopsy method with the determination of the level of circulating tumor DNA is a promising diagnostic method that needs to evaluate the results of an initiated randomized trial.Conclusion. The accumulation of knowledge base about the molecular patterns of UTC will help bridge the gap between the results of molecular genetic and clinical diagnostics. Molecular changes in the transitional cell UTC demonstrates a high potential for determining the timing of tumor recurrence, assessing disease-free survival of patients and for planning the resource base of the healthcare system.

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