Skip to main content
Erschienen in:

13.03.2019 | Original Article

CD163+ macrophages predict a poor prognosis in patients with primary T1 high-grade urothelial carcinoma of the bladder

verfasst von: Guoliang Yang, Lianhua Zhang, Mengyao Liu, Qiang liu, Xuehui Duan, Juanjie Bo

Erschienen in: World Journal of Urology | Ausgabe 12/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Macrophages are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study investigates the prognostic value of tumor-infiltrated CD163+ macrophages in patients with T1 high-grade (T1HG) bladder cancer.

Methods

CD163+ macrophages were assessed by immunohistochemistry in 94 T1HG bladder cancer samples. Kaplan–Meier analyses and Cox proportional hazards’ regression models were applied to evaluate recurrence-free survival, progression-free survival and disease-specific survival.

Results

With a median follow-up of 60 months, 37 (39.4%) patients experienced disease recurrence, 14 (14.9%) progression, 11 (11.7%) disease-specific mortality. High CD163+ macrophages were associated with higher risk of disease recurrence and progression (P < 0.05, for both). In multivariate Cox proportional hazards regression analysis, high CD163+ macrophages were a significant negative predictor of recurrence-free survival, progression-free survival and disease-specific survival (P < 0.05 for all).

Conclusion

CD163+ macrophages are a poor prognostic factor in T1HG bladder cancer. This finding provide the ground for further testing it in predicting the outcome of this challenging disease.
Literatur
1.
Zurück zum Zitat Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30CrossRef Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30CrossRef
2.
Zurück zum Zitat Svatek RS, Hollenbeck BK, Holmang S, Lee R, Kim SP, Stenzl A et al (2014) The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol 66:253–262CrossRef Svatek RS, Hollenbeck BK, Holmang S, Lee R, Kim SP, Stenzl A et al (2014) The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol 66:253–262CrossRef
3.
Zurück zum Zitat Kulkarni GS, Hakenberg OW, Gschwend JE, Thalmann G, Kassouf W, Kamat A et al (2010) An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol 57:60–70CrossRef Kulkarni GS, Hakenberg OW, Gschwend JE, Thalmann G, Kassouf W, Kamat A et al (2010) An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol 57:60–70CrossRef
4.
Zurück zum Zitat Denzinger S, Fritsche HM, Otto W, Blana A, Wieland WF, Burger M (2008) Early versus deferred cystectomy for initial high-risk pT1G3 urothelial carcinoma of the bladder: do risk factors define feasibility of bladder-sparing approach? Eur Urol 53:146–152CrossRef Denzinger S, Fritsche HM, Otto W, Blana A, Wieland WF, Burger M (2008) Early versus deferred cystectomy for initial high-risk pT1G3 urothelial carcinoma of the bladder: do risk factors define feasibility of bladder-sparing approach? Eur Urol 53:146–152CrossRef
5.
Zurück zum Zitat Canter D, Egleston B, Wong YN, Smaldone MC, Simhan J, Greenberg RE et al (2013) Use of radical cystectomy as initial therapy for the treatment of high-grade T1 urothelial carcinoma of the bladder: a SEER database analysis. Urol Oncol 31:866–870CrossRef Canter D, Egleston B, Wong YN, Smaldone MC, Simhan J, Greenberg RE et al (2013) Use of radical cystectomy as initial therapy for the treatment of high-grade T1 urothelial carcinoma of the bladder: a SEER database analysis. Urol Oncol 31:866–870CrossRef
6.
Zurück zum Zitat Bhardwaj N (2007) Harnessing the immune system to treat cancer. J Clin Investig 117:1130–1136CrossRef Bhardwaj N (2007) Harnessing the immune system to treat cancer. J Clin Investig 117:1130–1136CrossRef
7.
Zurück zum Zitat De Palma M, Lewis CE (2013) Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell 23:277–286CrossRef De Palma M, Lewis CE (2013) Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell 23:277–286CrossRef
8.
Zurück zum Zitat Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141:39–51CrossRef Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141:39–51CrossRef
9.
Zurück zum Zitat Shabo I, Olsson H, Sun XF, Svanvik J (2009) Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time. Int J Cancer 125:1826–1831CrossRef Shabo I, Olsson H, Sun XF, Svanvik J (2009) Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time. Int J Cancer 125:1826–1831CrossRef
10.
Zurück zum Zitat Comito G, Giannoni E, Segura CP, Barcellos-de-Souza P, Raspollini MR, Baroni G et al (2014) Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene 33:2423–2431CrossRef Comito G, Giannoni E, Segura CP, Barcellos-de-Souza P, Raspollini MR, Baroni G et al (2014) Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene 33:2423–2431CrossRef
11.
Zurück zum Zitat Lau SK, Chu PG, Weiss LM (2004) CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol 122:794–801CrossRef Lau SK, Chu PG, Weiss LM (2004) CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol 122:794–801CrossRef
12.
Zurück zum Zitat Ambarus CA, Krausz S, van Eijk M, Hamann J, Radstake TR, Reedquist KA et al (2012) Systematic validation of specific phenotypic markers for in vitro polarized human macrophages. J Immunol Methods 375:196–206CrossRef Ambarus CA, Krausz S, van Eijk M, Hamann J, Radstake TR, Reedquist KA et al (2012) Systematic validation of specific phenotypic markers for in vitro polarized human macrophages. J Immunol Methods 375:196–206CrossRef
13.
Zurück zum Zitat Lan C, Huang X, Lin S, Huang H, Cai Q, Wan T et al (2013) Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer. Technol Cancer Res Treat 12:259–267CrossRef Lan C, Huang X, Lin S, Huang H, Cai Q, Wan T et al (2013) Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer. Technol Cancer Res Treat 12:259–267CrossRef
14.
Zurück zum Zitat Sugimoto M, Mitsunaga S, Yoshikawa K, Kato Y, Gotohda N, Takahashi S et al (2014) Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas. Eur J Cancer 50:1900–1908CrossRef Sugimoto M, Mitsunaga S, Yoshikawa K, Kato Y, Gotohda N, Takahashi S et al (2014) Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas. Eur J Cancer 50:1900–1908CrossRef
15.
Zurück zum Zitat Ding P, Wang W, Wang J, Yang Z, Xue L (2014) Expression of tumor-associated macrophage in progression of human glioma. Cell Biochem Biophys 70:1625–1631CrossRef Ding P, Wang W, Wang J, Yang Z, Xue L (2014) Expression of tumor-associated macrophage in progression of human glioma. Cell Biochem Biophys 70:1625–1631CrossRef
16.
Zurück zum Zitat Balermpas P, Rodel F, Liberz R, Oppermann J, Wagenblast J, Ghanaati S et al (2014) Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences. Br J Cancer 111:1509–1518CrossRef Balermpas P, Rodel F, Liberz R, Oppermann J, Wagenblast J, Ghanaati S et al (2014) Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences. Br J Cancer 111:1509–1518CrossRef
17.
Zurück zum Zitat Hu Y, He MY, Zhu LF, Yang CC, Zhou ML, Wang Q et al (2016) Tumor-associated macrophages correlate with the clinicopathological features and poor outcomes via inducing epithelial to mesenchymal transition in oral squamous cell carcinoma. J Exp Clin Cancer Res CR 35:12CrossRef Hu Y, He MY, Zhu LF, Yang CC, Zhou ML, Wang Q et al (2016) Tumor-associated macrophages correlate with the clinicopathological features and poor outcomes via inducing epithelial to mesenchymal transition in oral squamous cell carcinoma. J Exp Clin Cancer Res CR 35:12CrossRef
18.
Zurück zum Zitat Ma C, Komohara Y, Ohnishi K, Shimoji T, Kuwahara N, Sakumura Y et al (2016) Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma. Cancer Sci 107:700–707CrossRef Ma C, Komohara Y, Ohnishi K, Shimoji T, Kuwahara N, Sakumura Y et al (2016) Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma. Cancer Sci 107:700–707CrossRef
19.
Zurück zum Zitat May M, Brookman-Amissah S, Roigas J, Hartmann A, Storkel S, Kristiansen G et al (2010) Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: a multicentre study comparing the 1973 and 2004 World Health Organisation classifications. Eur Urol 57:850–858CrossRef May M, Brookman-Amissah S, Roigas J, Hartmann A, Storkel S, Kristiansen G et al (2010) Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: a multicentre study comparing the 1973 and 2004 World Health Organisation classifications. Eur Urol 57:850–858CrossRef
20.
Zurück zum Zitat Chou R, Buckley D, Fu R, Gore JL, Gustafson K, Griffin J et al (2015) Emerging approaches to diagnosis and treatment of non-muscle-invasive bladder cancer. Agency for Healthcare Research and Quality, Rockville, MD Chou R, Buckley D, Fu R, Gore JL, Gustafson K, Griffin J et al (2015) Emerging approaches to diagnosis and treatment of non-muscle-invasive bladder cancer. Agency for Healthcare Research and Quality, Rockville, MD
21.
Zurück zum Zitat Zuiverloon TC, Nieuweboer AJ, Vekony H, Kirkels WJ, Bangma CH, Zwarthoff EC (2012) Markers predicting response to bacillus Calmette-Guerin immunotherapy in high-risk bladder cancer patients: a systematic review. Eur Urol 61:128–145CrossRef Zuiverloon TC, Nieuweboer AJ, Vekony H, Kirkels WJ, Bangma CH, Zwarthoff EC (2012) Markers predicting response to bacillus Calmette-Guerin immunotherapy in high-risk bladder cancer patients: a systematic review. Eur Urol 61:128–145CrossRef
22.
Zurück zum Zitat Fristrup N, Ulhoi BP, Birkenkamp-Demtroder K, Mansilla F, Sanchez-Carbayo M, Segersten U et al (2012) Cathepsin E, maspin, Plk1, and survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer. Am J Pathol 180:1824–1834CrossRef Fristrup N, Ulhoi BP, Birkenkamp-Demtroder K, Mansilla F, Sanchez-Carbayo M, Segersten U et al (2012) Cathepsin E, maspin, Plk1, and survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer. Am J Pathol 180:1824–1834CrossRef
23.
Zurück zum Zitat van Rhijn BW, Liu L, Vis AN, Bostrom PJ, Zuiverloon TC, Fleshner NE et al (2012) Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer. BJU Int 110:1169–1176CrossRef van Rhijn BW, Liu L, Vis AN, Bostrom PJ, Zuiverloon TC, Fleshner NE et al (2012) Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer. BJU Int 110:1169–1176CrossRef
24.
Zurück zum Zitat Oldenhuis CN, Oosting SF, Gietema JA, de Vries EG (2008) Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer 44:946–953CrossRef Oldenhuis CN, Oosting SF, Gietema JA, de Vries EG (2008) Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer 44:946–953CrossRef
25.
Zurück zum Zitat Hewitt SM (2012) Tissue microarrays as a tool in the discovery and validation of predictive biomarkers. Methods Mol Biol 823:201–214CrossRef Hewitt SM (2012) Tissue microarrays as a tool in the discovery and validation of predictive biomarkers. Methods Mol Biol 823:201–214CrossRef
Metadaten
Titel
CD163+ macrophages predict a poor prognosis in patients with primary T1 high-grade urothelial carcinoma of the bladder
verfasst von
Guoliang Yang
Lianhua Zhang
Mengyao Liu
Qiang liu
Xuehui Duan
Juanjie Bo
Publikationsdatum
13.03.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
World Journal of Urology / Ausgabe 12/2019
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-018-02618-1

Neu im Fachgebiet Urologie

Genügt die biparametrische MRT für die Prostatadiagnostik?

Die multiparametrische Magnetresonanztomografie hat einen festen Platz im Screening auf klinisch signifikante Prostatakarzinome. Ob auch ein biparametrisches Vorgehen ausreicht, ist in einer Metaanalyse untersucht worden.

Große Trinkmengen bei Blasentumoren möglicherweise von Nachteil

Beim nicht-muskelinvasiven Blasenkrebs scheint eine hohe Flüssigkeitszufuhr keinen schützenden Effekt in Bezug auf das Risiko eines Rezidivs oder einer Krankheitsprogression zu haben. Eine niederländische Studie legt sogar nahe, dass große Trinkmengen das Fortschreiten der Erkrankung begünstigen könnten.

Urintest auf Prostatakrebs funktioniert mit Erststrahlurin

Ein auf die Expression von 18 Genen gestützter Urintest auf klinisch signifikanten Prostatakrebs könnte offenbar auch in Anwendung auf Erststrahlurin dazu dienen, unnötige Biopsien zu vermeiden.

Hohe Atrophierate nach Hodentorsion im Kindesalter

Auf längere Sicht ist die Atrophierate nach einer Hodentorsion pädiatrischer Patienten erschreckend hoch. Das hat eine Studie mit jahrelanger Nachbeobachtung ergeben. Entscheidend ist die Zeit, die bis zur Detorsion verstreicht.

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.