Cellular senescence in testicular cancer. Is there a correlation with the preoperative markers and the extent of the tumor? An experimental study

Published: March 4, 2024
Abstract Views: 336
PDF: 112
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.


Purpose: The aim of this experimental study is to investigate the correlation between the presence of senescent cells and the tumor size, the lymphovascular invasion (LVI), the invasion of rete testis (RTI), the preoperative tumor markers or pathological stage in patients who underwent orchiectomy for malignant purposes.
Methods: This experimental study included patients with a history of radical orchiectomy performed from January 2011 to January 2019. The testicular tissue specimens underwent an immunohistopathological process for the detection of the presence of cellular senescence. Besides, the tumor size, the histopathological type, the pathological stage of the tumor and the presence of Lymphovascular (LVI) or rete testis (RTI) invasions were also recorded. Additionally, the preoperative serum levels of alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were recorded. After the completion of immunohistochemical analysis, the rate of senescent cells in each specimen was also recorded.
Results: The mean senescent cell rate was estimated to be 14.11±11.32% and 15.46±10.58% in patients with presence of LVI or absence of LVI, respectively (p=0.46). The mean senescent cell rate was calculated at 18.13±12.26% and 12.56±9.38% (p=0.096) in patients with presence of RTI or absence of RTI, respectively. The mean senescent cell rate in the pT1 group was calculated at 14.58 ± 9.82%, while in T2 and T3 groups the mean senescent cell rate was estimated to be 15.22 ± 12.03% and 15.35 ± 14.21%, respectively (p=0.98). A statistically significant correlation was detected between the senescence rate and the tumor size (Pearson score 0.40, p=0.027) and between the rate of senescent cells and the preoperative level of lactate dehydrogenase (LDH) (Pearson score -0.53, p=0.002).
Conclusions: The presence of cellular senescence was correlated with the extent of the testicular tumor in terms of tumor size as well as the preoperative level of the LDH serum marker.

Biggs ML SS. Cancer of the testis. In: LAG Ries, J Young, GE Keel, et al., Editors. SEER survival monograph: cancer survival among adults: US SEER Program, 1988-2001, patient and tumor characteristics. National Cancer Institute, Bethesda: 2007; p. 165-70.

EAU Guidelines. Presented at the EAU Annual Congress Milan 2023. EAU Guidelines Office, Arnhem, the Netherlands.

Milose JC, Filson CP, Weizer AZ, Hafez KS, Montgomery JS. Role of biochemical markers in testicular cancer: diagnosis, staging, andsurveillance. Open Access J Urol. 2011;4:1-8. DOI: https://doi.org/10.2147/RRU.S15063

Germa-Lluch JR, Garcia del Muro X, Maroto P, et al. Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG). Eur Urol. 2002 42:553-62. DOI: https://doi.org/10.1016/S0302-2838(02)00439-6

Lempiainen A, Stenman UH, Blomqvist C, Hotakainen K. Free beta-subunit of human chorionic gonadotropin in serum is a diagnostically sensitive marker of seminomatous testicular cancer. Clin Chem. 2008;54:1840-3. DOI: https://doi.org/10.1373/clinchem.2008.108548

Carl J, Christensen TB, von der Maase H. Cisplatinum dose dependent response in germ cell cancer evaluated by tumour marker modelling. Acta Oncol. 1992;31:749-53. DOI: https://doi.org/10.3109/02841869209083865

Gorgoulis VG, Halazonetis TD. Oncogene-induced senescence: the bright and dark side of the response. Curr Opin Cell Biol. 2010;22:816-27. DOI: https://doi.org/10.1016/j.ceb.2010.07.013

Georgakopoulou EA, Tsimaratou K, Evangelou K, et al. Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues. Aging (Albany NY). 2013; 5:37-50. DOI: https://doi.org/10.18632/aging.100527

Zampetidis CP, Galanos P, Angelopoulou A, et al. A recurrent chromosomal inversion suffices for driving escape from oncogeneinduced senescence via subTAD reorganization. Mol Cell. 2021;81:4907-23. DOI: https://doi.org/10.1016/j.molcel.2021.10.017

Myrianthopoulos V, Evangelou K, Vasileiou PVS, et al. Senescence and senotherapeutics: a new field in cancer therapy. Pharmacol Ther. 2019;193:31-49. DOI: https://doi.org/10.1016/j.pharmthera.2018.08.006

Savelyeva AV, Medvedev KE. Seminoma subtypes differ in the organization and functional state of the immune microenvironment. 3 Biotech. 2023;13:110. DOI: https://doi.org/10.1007/s13205-023-03530-1

Majumder PK, Grisanzio C, O'Connell F, et al. A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression. Cancer Cell. 2008;14:146-55. DOI: https://doi.org/10.1016/j.ccr.2008.06.002

Kohli J, Wang B, Brandenburg SM, et al. Algorithmic assessment of cellular senescence in experimental and clinical specimens. Nat Protoc. 2021;16:2471-98. DOI: https://doi.org/10.1038/s41596-021-00505-5

Evangelou K, Lougiakis N, Rizou SV, et al. Robust, universal biomarker assay to detect senescent cells in biological specimens. Aging Cell. 2017;16:192-7. DOI: https://doi.org/10.1111/acel.12545

Bartkova J, Thullberg M, Rajpert-De Meyts E, et al. Cell cycle regulators in testicular cancer: loss of p18INK4C marks progression from carcinoma in situ to invasive germ cell tumours. Int J Cancer. 2000;85:370-5. DOI: https://doi.org/10.1002/(SICI)1097-0215(20000201)85:3<370::AID-IJC13>3.0.CO;2-A

Hilbold E, Bergmann M, Fietz D, et al. Immunolocalization of DMRTB1 in human testis with normal and impaired spermatogenesis. Andrology. 2019;7:428-40. DOI: https://doi.org/10.1111/andr.12617

Paltiel HJ, Diamond DA, Di Canzio J, et al. Testicular volume: comparison of orchidometer and US measurements in dogs. Radiology. 2002;222:114-9. DOI: https://doi.org/10.1148/radiol.2221001385

Gorgoulis V, Adams PD, Alimonti A, et al. Cellular Senescence: Defining a Path Forward. Cell. 2019;179:813-27. DOI: https://doi.org/10.1016/j.cell.2019.10.005

Mourkioti I, Polyzou A, Veroutis D, et al. A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer. J Exp Clin Cancer Res. 2023;42:187. DOI: https://doi.org/10.1186/s13046-023-02769-z

Evangelou K, Belogiannis K, Papaspyropoulos A, et al. Escape from senescence: molecular basis and therapeutic ramifications. J Pathol. 2023;260:649-65. DOI: https://doi.org/10.1002/path.6164

Coppe JP, Desprez PY, Krtolica A, Campisi J. The senescenceassociated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99-118. DOI: https://doi.org/10.1146/annurev-pathol-121808-102144

Galanos P, Pappas G, Polyzos A, et al. Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability. Genome Biol. 2018;19:37. DOI: https://doi.org/10.1186/s13059-018-1401-9

von Eyben FE, Parraga-Alava J. Meta-Analysis of Gene Expressions in Testicular Germ Cell Tumor Histologies. Int J Mol Sci. 2020;21:4487. DOI: https://doi.org/10.3390/ijms21124487

Haugstetter AM, Loddenkemper C, Lenze D, et al. Cellular senescence predicts treatment outcome in metastasised colorectal cancer. Br J Cancer. 2010;103:505-9. DOI: https://doi.org/10.1038/sj.bjc.6605784

Collado M, Gil J, Efeyan A, et al. Tumour biology: senescence in premalignant tumours. Nature. 2005;436:642. DOI: https://doi.org/10.1038/436642a

Brockelmann PJ, Angelopoulou MK, Vassilakopoulos TP. Prognostic factors in Hodgkin lymphoma. Semin Hematol. 2016;53:155-64. DOI: https://doi.org/10.1053/j.seminhematol.2016.05.003

Tatanis, V., Veroutis, D., Pantelis, P., Theocharous, G., Sarlanis, H., Georgiou, A., Peteinaris, A., Natsos, A., Moulavasilis, N., Kavantzas, N., Kotsinas, A., & Adamakis, I. (2024). Cellular senescence in testicular cancer. Is there a correlation with the preoperative markers and the extent of the tumor? An experimental study. Archivio Italiano Di Urologia E Andrologia, 96(1). https://doi.org/10.4081/aiua.2024.12246


Download data is not yet available.