Cellular Senescence in Germ Cell Neoplasia In Situ (GCNIS) and Other Histological Types of Testicular Cancer.

Background and Objectives: The presence and contribution of senescent cells in premalignant lesions is well documented, but not in germ cell neoplasia in situ. The purpose of this study is to identify the presence of senescent cells in pre-malignant testicular conditions and in different histological types of testicular cancer. Materials and Methods: Thirty patients who underwent orchiectomy due to testicular tumors were included. Formalin-fixed paraffin-embedded (FFPE) testicular tissue for each patient was available. Sections from these specimens were examined by immunohistochemical analysis with the following markers: GL13 for cellular senescence, p21WAF1/Cip1 for cell cycle arrest, and Ki67 for cell proliferation. Results: Thirteen (43.3%) suffered from seminoma with a mean total proportion of GCNIS senescence of 20.81 ± 6.81%. In the group of embryonal testicular tumors, nine (30%) patients were included, with an average rate of 6.64 ± 5.42% of senescent cells in GCNIS. One (3.3%) patient suffered from chondrosarcoma in which 7.9% of GL13+ cells were detected in GCNIS. Four (13.4%) patients suffered from teratoma and three (10%) from yolk sac tumors, while GCNIS senescence was detected in a range of 4.43 ± 1.78% and 3.76 ± 1.37%, respectively. Conclusions: Cellular senescence was detected in both germ cell neoplasia in situ and testicular cancer, but was more prevalent within the premalignant lesions.

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

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.