https://doi.org/10.4081/aiua.2024.12246

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

Vol. 96 No. 1 (2024)
Published: March 4, 2024
Testicular cancer, cellular senescence, preoperative tumor markers, GL13, senescent cells
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Authors

Vasileios Tatanis
tatanisbas@gmail.com
https://orcid.org/0000-0002-8584-3888
Department of Urology, University of Patras, Greece.
Dimitris Veroutis
Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National Kapodistrian University of Athens (NKUA), Athens, Greece.
Pavlos Pantelis
Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National Kapodistrian University of Athens (NKUA), Athens, Greece.
George Theocharous
https://orcid.org/0009-0008-4518-8728
Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National Kapodistrian University of Athens (NKUA), Athens, Greece.
Helen Sarlanis
https://orcid.org/0000-0001-7197-939X
Department of Pathology, Medical School, National and Kapodistrian University, Athens, Greece.
Alexandros Georgiou
Department of Pathology, Medical School, National and Kapodistrian University, Athens, Greece.
Angelis Peteinaris
https://orcid.org/0000-0002-0427-4506
Department of Urology, University of Patras, Greece.
Anastasios Natsos
https://orcid.org/0000-0002-5845-7420
Department of Urology, University of Patras, Greece.
Napoleon Moulavasilis
https://orcid.org/0000-0002-1820-9027
1st Department of Urology, National and Kapodistrian University of Athens, Greece.
Nikolaos Kavantzas
Department of Pathology, Medical School, National and Kapodistrian University, Athens, Greece.
Athanassios Kotsinas
Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National Kapodistrian University of Athens (NKUA), Athens, Greece.
Ioannis Adamakis
1st Department of Urology, National and Kapodistrian University of Athens, Greece.

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.

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Citations

Crossref
Scopus
Google Scholar
Europe PMC
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

How to Cite

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
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