Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma

Abstract Background Urothelial carcinoma (UC) is a common type of malignant disease; however, the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) remain poorly understood because of its rarity. Methods To clarify the clinicopathological significance of granulocyte-c...

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Main Authors: Go Kobayashi, Yohei Sekino, Hikaru Nakahara, Kohei Kobatake, Keisuke Goto, Tetsutaro Hayashi, Kazuhiro Sentani, Nobuyuki Hinata
Format: Article
Language:English
Published: Springer 2024-12-01
Series:Journal of Cancer Research and Clinical Oncology
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Online Access:https://doi.org/10.1007/s00432-024-06045-1
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author Go Kobayashi
Yohei Sekino
Hikaru Nakahara
Kohei Kobatake
Keisuke Goto
Tetsutaro Hayashi
Kazuhiro Sentani
Nobuyuki Hinata
author_facet Go Kobayashi
Yohei Sekino
Hikaru Nakahara
Kohei Kobatake
Keisuke Goto
Tetsutaro Hayashi
Kazuhiro Sentani
Nobuyuki Hinata
author_sort Go Kobayashi
collection DOAJ
description Abstract Background Urothelial carcinoma (UC) is a common type of malignant disease; however, the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) remain poorly understood because of its rarity. Methods To clarify the clinicopathological significance of granulocyte-colony stimulating factor (G-CSF) in UTUC, we analyzed the expression and distribution of G-CSF in 112 upper tract urothelial carcinoma (UTUC) samples with immunohistochemistry. Results In normal urothelium, G-CSF expression was weak or absent, whereas high expression of G-CSF was observed in UTUC tissues, both in tumor cells (TCs) and stromal cells (SCs). G-CSF expression in the TCs and SCs was associated with nodular/flat morphology, high grade, advanced T stage, and lymphovascular invasion in UTUC. G-CSF expression in SCs was associated with poor prognosis and was an independent prognostic factor. Public data showed that G-CSF expression was also associated with decreased progression-free survival and disease-specific survival. A prognostic model was constructed by incorporating the presence or absence of G-CSF expression along with clinicopathologic factors, which allowed for a more accurate prediction of poor prognosis. We further showed that G-CSF expression was associated with a high Ki-67 labeling index and with PD-L1, HER2, and p53 expression in UTUC. Conclusion G-CSF expression in TCs and SCs may play a crucial role in UTUC tumor progression. Notably, stromal G-CSF expression showed significant prognostic value, even when compared to major clinicopathological factors, suggesting that the evaluation of G-CSF expression may contribute to clinical decision-making in patients with UTUC.
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spelling doaj-art-d37109a5b2644b02b64de552644a919d2025-02-09T12:10:31ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352024-12-01151111210.1007/s00432-024-06045-1Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinomaGo Kobayashi0Yohei Sekino1Hikaru Nakahara2Kohei Kobatake3Keisuke Goto4Tetsutaro Hayashi5Kazuhiro Sentani6Nobuyuki Hinata7Laboratory of Molecular Pathology, Department of Molecular Biosciences, Radiation Effects Research FoundationDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Clinical and Molecular Genetics, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityAbstract Background Urothelial carcinoma (UC) is a common type of malignant disease; however, the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) remain poorly understood because of its rarity. Methods To clarify the clinicopathological significance of granulocyte-colony stimulating factor (G-CSF) in UTUC, we analyzed the expression and distribution of G-CSF in 112 upper tract urothelial carcinoma (UTUC) samples with immunohistochemistry. Results In normal urothelium, G-CSF expression was weak or absent, whereas high expression of G-CSF was observed in UTUC tissues, both in tumor cells (TCs) and stromal cells (SCs). G-CSF expression in the TCs and SCs was associated with nodular/flat morphology, high grade, advanced T stage, and lymphovascular invasion in UTUC. G-CSF expression in SCs was associated with poor prognosis and was an independent prognostic factor. Public data showed that G-CSF expression was also associated with decreased progression-free survival and disease-specific survival. A prognostic model was constructed by incorporating the presence or absence of G-CSF expression along with clinicopathologic factors, which allowed for a more accurate prediction of poor prognosis. We further showed that G-CSF expression was associated with a high Ki-67 labeling index and with PD-L1, HER2, and p53 expression in UTUC. Conclusion G-CSF expression in TCs and SCs may play a crucial role in UTUC tumor progression. Notably, stromal G-CSF expression showed significant prognostic value, even when compared to major clinicopathological factors, suggesting that the evaluation of G-CSF expression may contribute to clinical decision-making in patients with UTUC.https://doi.org/10.1007/s00432-024-06045-1Clinicopathological significanceG-CSFImmunohistochemistryPrognostic markerUpper tract urothelial carcinoma
spellingShingle Go Kobayashi
Yohei Sekino
Hikaru Nakahara
Kohei Kobatake
Keisuke Goto
Tetsutaro Hayashi
Kazuhiro Sentani
Nobuyuki Hinata
Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma
Journal of Cancer Research and Clinical Oncology
Clinicopathological significance
G-CSF
Immunohistochemistry
Prognostic marker
Upper tract urothelial carcinoma
title Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma
title_full Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma
title_fullStr Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma
title_full_unstemmed Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma
title_short Distribution and clinicopathological characteristics of G-CSF expression in tumor cells and stromal cells in upper tract urothelial carcinoma
title_sort distribution and clinicopathological characteristics of g csf expression in tumor cells and stromal cells in upper tract urothelial carcinoma
topic Clinicopathological significance
G-CSF
Immunohistochemistry
Prognostic marker
Upper tract urothelial carcinoma
url https://doi.org/10.1007/s00432-024-06045-1
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