Testicular Germ Cell Cancer Research Articles

The Utility of Immuno-Nutritional Scores in Patients with Testicular Germ Cell Tumors

Background: Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP) is an accessible score that is easily reproducible from routine laboratory testing while also reflecting patients’ immune-nutritional status. Along with other immuno-nutritional scores, such as the Prognostic Nutrition Index (PNI), HALP has been associated with a number of clinical and pathological features. The goal of our study was to evaluate the prognostic utility of HALP and PNI scores in testicular germ cell cancer (GCT) patients. Methods: This case-only study included 203 testicular GCT patients who were classified according to the disease stage and HALP and PNI cut-offs. Complete blood count and albumin concentration were routinely determined. Results: The values of HALP and PNI significantly differed among different clinical stages (p < 0.05). Moreover, they clearly exposed a significantly higher risk of advanced clinical stage development for those testicular GCT patients with lower values of HALP and PNI (p < 0.05). Finally, lower score levels were associated with larger tumor size (p < 0.05). Conclusion: Our investigation could provide evidence that specific immune-nutritional scores can help distinguish individuals diagnosed with testicular GCT who are more likely to be identified with advanced disease stages.

Primary retroperitoneal lymph node dissection in testicular germ cell cancer in clinical stage IIA/B-renaissance of an established treatment?

The guideline-recommended treatment of choice for clinical stage IIA/B testicular germ cell tumors is chemotherapy with three cycles of PEB/four cycles of PE or, alternatively, radiation for seminomas. Despite their high curative efficacy, both options are associated with significant long-term toxicities. We evaluated the functional and oncological outcomes of primary retroperitoneal lymph node dissection (RPLND) as atherapeutic alternative. Between 2018 and 2022, 76patients (n = 34 seminomas, n = 42 nonseminomas) underwent primary RPLND for marker-negative clinical stage IIA/B testicular germ cell cancer. All patients underwent nerve-sparing RPLND with a unilateral or bilateral template dissection and had a follow-up ≥ 3months. None of the patients received adjuvant chemotherapy. In 24patients, the serum concentration of miR371a-3p was evaluated preoperatively. Follow-up was performed according to EAU guidelines. Median age and median follow-up were 30.1 (17-62)years and 29.3 (3-72)months, respectively. Mean operation time, blood loss, and duration of hospitalization were 131 (105-195) min, < 150 ml, and 4.5 (3-9) days, respectively. AClavien-Dindo IIIa complication was experienced by 8 (10.9%) patients. Antegrade ejaculation was preserved in 90.8%. Amean number of 19(7-68) lymph nodes were dissected. The mean number of positive lymph nodes was 1.1 (1-5), and the mean diameter of positive lymph nodes was 2.4 (0.8-4.6)cm. Eleven (14.5%) patients had stage pN0 (3/34 seminomas, 8/42 nonseminomas). In 24/27patients (88.9%) miR371 was positive, and it was negative in 4/4 with pN0 and 3/3 (100%) with teratoma. An outfield relapse was experienced by 7patients (9.2%), who then received salvage chemotherapy. Primary RPLND for marker-negative clinical stageIIA/B germ cell tumors results in high cure rates without adjuvant chemotherapy and is associated with alow rate of complications if performed in experienced hands. Therefore, primary RPLND should be included in the management of these patients.

Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.

SEOM-GG clinical guidelines for the management of germ-cell testicular cancer (2023)

Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment. Patients with persistent markers after orchiectomy or advanced disease at diagnosis should be staged and classified according to the IGCCCG prognostic classification. BEP is the most recommended chemotherapy, but other schedules such as EP or VIP may be used to avoid bleomycin in some patients. Efforts should be made to avoid unnecessary delays and dose reductions wherever possible. Insufficient marker decline after each cycle is associated with poor prognosis. Management of residual masses after chemotherapy differs between patients with seminoma and non-seminoma tumors. Patients at high risk of relapse, those with refractory tumors, or those who relapse after chemotherapy should be managed by multidisciplinary teams in experienced centers. Salvage treatment for these patients includes conventional-dose chemotherapy (TIP) and/or high-dose chemotherapy, although the best regimen and strategy for each subgroup of patients is not yet well established. In late recurrences, early complete surgical resection should be performed when feasible. Given the high cure rate of TGCT, oncologists should work with patients to prevent and identify potential long-term side effects of the treatment. The above recommendations also apply to extragonadal retroperitoneal and mediastinal tumors.

Plasma metabolites and risk of seven cancers: a two-sample Mendelian randomization study among European descendants

BackgroundWhile circulating metabolites have been increasingly linked to cancer risk, the causality underlying these associations remains largely uninterrogated.MethodsWe conducted a comprehensive 2-sample Mendelian randomization (MR) study to evaluate the potential causal relationship between 913 plasma metabolites and the risk of seven cancers among European-ancestry individuals. Data on variant-metabolite associations were obtained from a genome-wide association study (GWAS) of plasma metabolites among 14,296 subjects. Data on variant-cancer associations were gathered from large-scale GWAS consortia for breast (N = 266,081), colorectal (N = 185,616), lung (N = 85,716), ovarian (N = 63,347), prostate (N = 140,306), renal cell (N = 31,190), and testicular germ cell (N = 28,135) cancers. MR analyses were performed with the inverse variance-weighted (IVW) method as the primary strategy to identify significant associations at Bonferroni-corrected P < 0.05 for each cancer type separately. Significant associations were subjected to additional scrutiny via weighted median MR, Egger regression, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and reverse MR analyses. Replication analyses were performed using an independent dataset from a plasma metabolite GWAS including 8,129 participants of European ancestry.ResultsWe identified 94 significant associations, suggesting putative causal associations between 66 distinct plasma metabolites and the risk of seven cancers. Remarkably, 68.2% (45) of these metabolites were each associated with the risk of a specific cancer. Among the 66 metabolites, O-methylcatechol sulfate and 4-vinylphenol sulfate demonstrated the most pronounced positive and negative associations with cancer risk, respectively. Genetically proxied plasma levels of these two metabolites were significantly associated with the risk of lung cancer and renal cell cancer, with an odds ratio and 95% confidence interval of 2.81 (2.33–3.37) and 0.49 (0.40–0.61), respectively. None of these 94 associations was biased by weak instruments, horizontal pleiotropy, or reverse causation. Further, 64 of these 94 were eligible for replication analyses, and 54 (84.4%) showed P < 0.05 with association patterns consistent with those shown in primary analyses.ConclusionsOur study unveils plausible causal relationships between 66 plasma metabolites and cancer risk, expanding our understanding of the role of circulating metabolites in cancer genetics and etiology. These findings hold promise for enhancing cancer risk assessment and prevention strategies, meriting further exploration.

EDITING CDKN1A AND RASD1 IN A CELL CULTURE SYSTEM

Abstract As an individual ages, there is a higher incidence of cancer and infertility. Testicular germ cell cancer rates have been rising year after year. According to the American Cancer Society 1 of every 250 males will develop testicular cancer during their lifetime. In this research project, we aim to develop a molecular toolbox to analyze gene function in male germinal cells using a CRISPR/Cas9 cell culture system. This biotechnology allows for the targeted alteration and cutting of specific DNA strands. To achieve this, we will utilize cancer cell lines (SUSA and NT2/D1 testicular cancer cell lines) and knock out two genes of interest: cyclin-dependent kinase inhibitor 1 (CDKN1A) and ras-related dexamethasone-induced 1 (RASD1). Our objective is to investigate the effects of gene knockout on cell proliferation. For this purpose, we designed primers and single-guide RNAs using bioinformatic databases: Benchling and Chop Chop. The tools we used were employed to amplify human genomic DNA and assess the effectiveness of the guide RNAs through in vitro cutting of our genes of interest, followed by gel electrophoresis observations. Based on the results obtained from these experiments, our next step is to electroporate the guide RNA and Cas9 complex to alter gene function in our cell culture system. Through a better understanding of gene function in testicular cancer cell lines, we hope to inform future therapeutic targets for both testicular cancer and age-related infertility.

Communication network between pluripotency factors in Embryonic Stem Cell-like cells and their role in testicular germ cell cancer

Communication network between pluripotency factors in Embryonic Stem Cell-like cells and their role in testicular germ cell cancer

PB0958 The Efficacy of Thromboprophylaxis against Chemotherapy- Associated Thromboembolic Events in Germ Cell Testicular Cancers: A Meta-Analysis of Comparative Studies

PB0958 The Efficacy of Thromboprophylaxis against Chemotherapy- Associated Thromboembolic Events in Germ Cell Testicular Cancers: A Meta-Analysis of Comparative Studies

PB0925 The Impact of Clinicopathologic Factors on the Risk of Chemotherapy- Associated Thromboembolic Events in Germ Cell Testicular Cancers: A Pooled Analysis

PB0925 The Impact of Clinicopathologic Factors on the Risk of Chemotherapy- Associated Thromboembolic Events in Germ Cell Testicular Cancers: A Pooled Analysis

PB0959 The Pooled Estimate of Thromboembolic Events and Their Patterns in Advanced Germ Cell Testicular Cancers: A Proportional Meta-Analysis

PB0959 The Pooled Estimate of Thromboembolic Events and Their Patterns in Advanced Germ Cell Testicular Cancers: A Proportional Meta-Analysis

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: ‘neutral’ (n = 228) with normal sex hormone homeostasis, ‘testicle’ (n = 91) with elevated T and E2, low pituitary hormones, and finally ‘pituitary’ subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.

Novel approaches to redesign surveillance strategies following orchiectomy for localized testicular cancer: a narrative review.

Surveillance is the preferred management strategy for most men with clinical stage I testicular cancer after orchiectomy. However, frequent office visits, imaging tests, and laboratory studies place a significant burden on patients, which may contribute to poor compliance with guideline-recommended surveillance regimens. Identifying strategies to overcome these barriers may help improve quality of life, reduce costs, and improve adherence for patients. We reviewed evidence for three strategies that may help with surveillance redesign: telemedicine, implementing microRNA (miRNA) as a biomarker, and novel imaging protocols. A web-based literature search for novel imaging strategies, diagnostic utility of miRNA, and telehealth as they relate to early-stage testicular germ cell cancer was completed during the month of August 2022. We focused our search on contemporary PubMed-indexed and Google Scholar-registered manuscripts written in English. Supportive data sourced from current guideline statements were also included. Evidence was compiled for narrative review. Telemedicine is a safe and acceptable platform for urologic cancer follow-up care, but it requires further study specifically among men with testicular cancer. Access to care may either be improved or reduced depending on system- and patient-level characteristics and should be implemented with this in mind. miRNA may potentially be a helpful biomarker for men with localized disease, but further research on diagnostic accuracy and marker kinetics are needed before implementing it into routine surveillance strategies or using it to deviate from long-standing surveillance regiments. Novel imaging strategies with less frequent imaging and the use of magnetic resonance imaging (MRI) instead of computed tomography (CT) appear to be non-inferior in clinical trials. However, use of MRI requires expert radiologist availability and may be more costly with a lower ability to detect small, early recurrences when used in routine practice. Using telemedicine, integrating miRNA as a tumor marker, and adopting less intensive imaging strategies may improve guideline-concordant surveillance for men with localized testicular cancer. Future studies are needed to assess the risks and benefits of using these novel approaches separately or together.

The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study.

Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of GSTO1rs4925, GSTO2rs156697, and GSTO2rs2297235 polymorphisms with the risk for testicular GCT development, in 88 patients and 96 matched controls, through logistic regression models. We found that carriers of the GSTO1*C/A*C/C genotype exhibited an increased risk for testicular GCT development. Significant association with increased risk of testicular GCT was observed in carriers of GSTO2rs2297235*A/G*G/G genotype, and in carriers of combined GSTO2rs156697*A/G*G/G and GSTO2rs2297235*A/G*G/G genotypes. Haplotype H7 (GSTO1rs4925*C/GSTO2rs2297235*G/GSTO2rs156697*G) exhibited higher risk of testicular GCT, however, without significant association (p > 0.05). Finally, 51% of testicular GCT patients were the carriers of all three risk-associated genotypes, with 2.5-fold increased cumulative risk. In conclusion, the results of this pilot study suggest that GSTO polymorphisms might affect the protective antioxidant activity of GSTO isoenzymes, therefore predisposing susceptible individuals toward higher risk for testicular GCT development.

The Subtype Identity of Testicular Cancer Cells Determines Their Immunostimulatory Activity in a Coculture Model.

Testicular germ cell cancer (TGCC) is subdivided into several subtypes. While seminomatous germ cell tumors (SGCT) are characterized by an intensive infiltration of immune cells which constitute a pro-inflammatory tumor micromilieu (TME), immune cells in non-seminomatous germ cell tumors (NSGCT) are differently composed and less abundant. Previously, we have shown that the seminomatous cell line TCam-2 promotes T cell and monocyte activation in a coculture model, resulting in mutual interactions between both cell types. Here we set out to compare this feature of TCam-2 cells with the non-seminomatous cell line NTERA-2. Peripheral blood T cells or monocytes cocultured with NTERA-2 cells failed to secrete relevant amounts of pro-inflammatory cytokines, and significantly downregulated the expression of genes encoding activation markers and effector molecules. In contrast, immune cells cocultured with TCam-2 cells produced IL-2, IL-6 and TNFα, and strongly upregulated the expression of multiple pro-inflammatory genes. Furthermore, the expression of genes involved in proliferation, stemness and subtype specification remained unaltered in NTERA-2 cells during coculture with T cells or monocytes, indicating the absence of mutual interactions. Collectively, our findings uncover fundamental differences between SGCT and NSGCT in their capability to generate a pro-inflammatory TME, which possibly impacts the clinical features and prognosis of both TGCC subtypes.

Loss of liver kinase B1 in human seminoma.

Testicular cancer is a common malignancy of young males and is believed to be originated from defective embryonic or adult germ cells. Liver kinase B1 (LKB1) is a serine/threonine kinase and a tumor suppressor gene. LKB1 is a negative regulator of the mammalian target of rapamycin (mTOR) pathway, often inactivated in many human cancer types. In this study, we investigated the involvement of LKB1 in the pathogenesis of testicular germ cell cancer. We performed immunodetection of LKB1 protein in human seminoma samples. A 3D culture model of human seminoma was developed from TCam-2 cells, and two mTOR inhibitors were tested for their efficacy against these cancer cells. Western blot and mTOR protein arrays were used to show that these inhibitors specifically target the mTOR pathway. Examination of LKB1 showed reduced expression in germ cell neoplasia in situ lesions and seminoma compared to adjacent normal-appearing seminiferous tubules where the expression of this protein was present in the majority of germ cell types. We developed a 3D culture model of seminoma using TCam-2 cells, which also showed reduced levels of LKB1 protein. Treatment of TCam-2 cells in 3D with two well-known mTOR inhibitors resulted in reduced proliferation and survival of TCam-2 cells. Overall, our results support that downregulation or loss of LKB1 marks the early stages of the pathogenesis of seminoma, and the suppression of downstream signaling to LKB1 might be an effective therapeutic strategy against this cancer type.

Smoking as a prognostic factor for survival in patients with disseminated germ cell cancer.

We investigated the impact of smoking on overall survival (OS) in testicular germ cell cancer (TC) patients receiving first-line combination chemotherapy (bleomycin-etoposide-cisplatin [BEP]). Patients who received BEP for metastatic TC were identified in the Danish Testicular Cancer database. Information on smoking status at the time of diagnosis was obtained by medical record review. OS and cause of death were compared between current smokers and never-smokers. Of 1883 eligible patients, information on smoking status was available in 1156 patients, of whom 602 were current smokers. The 10-year OS was 92% in never-smokers compared with 83% in current smokers (P < .001) (hazard ratio for death = 1.85, 95% confidence interval = 1.29 to 2.66, P = .001). A higher proportion of current smokers died of TC compared with nonsmokers (P < .01). Smoking negatively affects survival after BEP in patients with disseminated TC. Vigorous smoking cessation programs are advocated in TC patients.

Endocannabinoid system and epigenetics in spermatogenesis and testicular cancer.

In mammals, male germ cell development starts during fetal life and is carried out in postnatal life with the formation of sperms. Spermatogenesis is the complex and highly orderly process during which a group of germ stem cells is set at birth, starts to differentiate at puberty. It proceeds through several stages: proliferation, differentiation, and morphogenesis and it is strictly regulated by a complex network of hormonal, autocrine and paracrine factors and it is associated with a unique epigenetic program. Altered epigenetic mechanisms or inability to respond to these factors can impair the correct process of germ development leading to reproductive disorders and/or testicular germ cell cancer. Among factors regulating spermatogenesis an emerging role is played by the endocannabinoid system (ECS). ECS is a complex system comprising endogenous cannabinoids (eCBs), their synthetic and degrading enzymes, and cannabinoid receptors. Mammalian male germ cells have a complete and active ECS which is modulated during spermatogenesis and that crucially regulates processes such as germ cell differentiation and sperm functions. Recently, cannabinoid receptor signaling has been reported to induce epigenetic modifications such as DNA methylation, histone modifications and miRNA expression. Epigenetic modifications may also affect the expression and function of ECS elements, highlighting the establishment of a complex mutual interaction. Here, we describe the developmental origin and differentiation of male germ cells and testicular germ cell tumors (TGCTs) focusing on the interplay between ECS and epigenetic mechanisms involved in these processes.

Impact of differing methodologies for serum miRNA-371a-3p assessment in stage I testicular germ cell cancer recurrence.

Current evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method. Sequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included. Using a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity. We conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation.

Expression of Intermediate Filaments in the Developing Testis and Testicular Germ Cell Cancer.

Cytokeratin and desmin expression have been associated with Sertoli cell maturity and the development of testicular germ cell cancer (TGCC). Thus, the present study aimed to characterize the expression of these intermediate filaments in normal testis development and TGCC. Cytokeratin and desmin were determined by immunohistochemistry and immunofluorescence in human fetal, and adult testis and tissue from patients with pre-invasive germ cell neoplasia in-situ (GCNIS) or invasive TGCC. Desmin was expressed in Sertoli cells of the human fetal testis, and the proportion of desmin expressing Sertoli cells was significantly reduced in the second trimester, compared with the first trimester (31.14% vs. 6.74%, p = 0.0016). Additionally, Desmin was expressed in the majority of Sertoli cells in the adult testis and TGCC samples. Cytokeratin was detected in Sertoli cells of human fetal testis but was not expressed in Sertoli cells of human adult testis. In patients with TGCC, cytokeratin was not expressed in Sertoli cells in tubules with active spermatogenesis but was detected in Sertoli cells in tubules containing GCNIS cells in patients with both pre-invasive and invasive TGCC. In conclusion, desmin was not associated with Sertoli cell maturation or progression to TGCC. However, cytokeratin appeared to be an indicator of impaired Sertoli cell maturation.