Markers of stem cells and their prognostic values for urothelial carcinomas of the urinary tract


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Abstract

The fundamental question about the origin of cancer stem cells of urothelial carcinomas with luminal remains open. So far, no convincing evidence has been found to determine whether these events occur in a single cell, presumably basal, or are realized in different precursor cells of the urothelium. The potential of a number of potential stem markers as cancer stem cells in urothelial carcinomas and their prognostic significance are currently being investigated. Aim. Our aim was to carry out a comparative analysis of the expression of stem markers in the molecular subtypes of urothelial carcinomas, including ALDH1A1, CXCR4, CD24, CD82, CD105, CD133, NANOG, OCT4 and SOX-2. In addition, the relationship between the pattern of expression and the pathological features of the tumor was determined. Patients and methods. Surgical specimens from 196 patients with a diagnosis of urothelial carcinoma of the renal pelvis and bladder were studied. Immunohistochemical study was performed on paraffin sections using the standard protocol. Antibodies against ALDH1A1, CD82, CD133, CXCR4, NANOG, OCT4, SOX2 («Abcam»), CD24, CD105 («Invitrogen»), CD31, CD34 («Novocastra») were used. Results. The stem cell markers used in the study were expressed in all molecular subtypes of urothelial carcinoma and there were no differences in frequency and intensity of expression between different phenotypes. However, the frequency and intensity of expression of the markers correlated with the tumor stage and the grade of cellular anaplasia. Conclusion. Our results confirm that cancer stem cells with basal phenotype are not an exclusive subpopulation in urothelial tumors. Other progenitor cells with the immunophenotype of intermediate and/ or umbrella cells can serve as cancer stem cells. These features of the expression in cancer stem cell markers will allow to develop new approaches to the treatment of urothelial carcinomas.

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About the authors

Yu. I Osmanov

I.M. Sechenov First Moscow State Medical University; Scientific Clinical Center of Russian Railways

Email: osmanovyouseef@yandex.ru
Ph.D., head of the Department of Pathology of Scientific Clinical Center of Russian Railways; assistant professor of Department of Pathology named after A.I. Strukov

E. A Kogan

I.M. Sechenov First Moscow State Medical University

Email: koganevg@gmail.com
MD, professor, Head of the Department of Pathology named after A.I. Strukov

L. M Rapoport

GBOU I.M. Sechenov First Moscow State Medical University

Email: leonidrapoport@yandex.ru
MD, professor, Deputy Director for Clinical Care

O. V Teodorovich

NUZ NKC OAO “RJD”, FGBOU DPO RMANPO; Scientific Clinical Center of Russian Railways

Email: teoclinic1@gmail.com
MD, professor, Chief of urologic center, Head of the Department of endoscopic urology

J. A Gaibov

Scientific Clinical Center of Russian Railways

Email: jam_morf@list.ru
pathologist at the Department of Pathology

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