Recent Advances in New Discovered Molecular Targets in Testicular Germ Cell Tumors

2018 ◽  
Vol 25 (5) ◽  
pp. 575-583 ◽  
Author(s):  
Paolo Chieffi
Keyword(s):  
Germ Cell ◽  
Primordial Germ Cells ◽  
Germ Cell Tumors ◽  
Molecular Targets ◽  
Testicular Germ Cell Tumor ◽  
Research Literature ◽  
Testicular Germ Cell ◽  
Solid Malignancy ◽  
Bibliographic Data ◽  
New Biomarkers

Background: Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Methods: I undertook a search of bibliographic data from peer-reviewed research literature. Results: Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies. Conclusion: A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment.

scholarly journals Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study

2021 ◽  
Vol 27 ◽  
pp. 107602962110247
Author(s):  
Hikmat Abdel-Razeq ◽  
Faris Tamimi ◽  
Rashid Abdel-Razeq ◽  
Samer Salah ◽  
Zaid Omari ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Germ Cell ◽  
Metastatic Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Tumor Burden ◽  
Testicular Tumors ◽  
Testicular Germ Cell ◽  
Node Positive ◽  
Age Range

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher ( P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

scholarly journals Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
João Lobo ◽  
Vera Constâncio ◽  
Pedro Leite-Silva ◽  
Rita Guimarães ◽  
Mariana Cantante ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Complete Response ◽  
Differential Analysis ◽  
Testicular Germ Cell ◽  
Tissue Samples ◽  
Tumor Patient ◽  
Resistant Disease ◽  
Response To Chemotherapy

AbstractTesticular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.

Testicular Germ Cell Tumor and down Syndrome

2000 ◽  
Vol 86 (5) ◽  
pp. 431-433 ◽  
Author(s):  
María José Villanueva ◽  
Fátima Navarro ◽  
Antonio Sánchez ◽  
Mariano Provencio ◽  
Félix Bonilla ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Medical Literature ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
English Medical Literature

The association between Down syndrome and testicular germ cell tumors may be more frequent than expected according to chance, but few reports have focused on this excess. We report two cases of this association and review the English medical literature.

Evidence for Altered Hypothalamic-Hypophyseal-Gonadal Axis in Untreated Patients with Testicular Germ-Cell Tumor

1989 ◽  
Vol 75 (5) ◽  
pp. 505-509
Author(s):  
Sergio Crispino ◽  
Gabriele Tancini ◽  
Sandro Barni ◽  
Paolo Lissoni
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Venous Blood ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Significant Difference

To investigate the function of the hypothalamic-hypophyseal-gonadal axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (GnRH) in 12 untreated patients with testicular cancer (5 seminomas and 7 non-seminomas). GnRH was given i.v. at a dose of 100 μg as a bolus, and venous blood samples were collected at 0, 20, 60, and 120 min. As controls, 14 healthy males were studied. Basal levels of testosterone, estradiol and prolactin were also detected in each patient. Hormonal serum concentrations were measured by the radioimmunoassay. Mean basal testosterone, estradiol and prolactin levels were not significantly different from those of controls. Patients had a lower FSH and LH peak after GnRH than controls, without, however, any significant difference. As regards histology, nonseminoma patients lacked an FSH response to GnRH and had statistically lower mean peak levels than controls. Moreover, non-seminoma patients had statistically lower mean peak values of LH after GnRH than controls. These data show that patients with testicular germ cell tumor, and more particularly those with non-seminomas, have an altered function of the hypothalamic-hypophyseal-gonadal axis, which is already present prior to therapy. Further studies, particularly in stage I patients treated only with orchiectomy, should be performed to confirm and better define the Physiopathologic significance of the altered hypothalamic-hypophyseal-gonadal axis in testicular cancer and to clarify the alteration of fertility, which is frequently present before treatment.

scholarly journals Rare inactivating PDE11A variants associated with testicular germ cell tumors

2015 ◽  
Vol 22 (6) ◽  
pp. 909-917 ◽  
Author(s):  
Anand Pathak ◽  
Douglas R Stewart ◽  
Fabio R Faucz ◽  
Paraskevi Xekouki ◽  
Sara Bass ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Testicular Tissue ◽  
Transcript Variant ◽  
Coding Region ◽  
Testicular Germ Cell ◽  
Rare Mutations ◽  
Gene Study

Germline inactivating mutations of isoform 4 of phosphodiesterase (PDE) 11A (coded by the PDE11A gene) have been associated with familial adrenocortical tumors and familial testicular cancer. Testicular tissue is unique in expressing all four isoforms of PDE11A. In a prior candidate gene study of 94 familial testicular germ cell tumor (TGCT) subjects, we identified a significant association between the presence of functionally abnormal variants in PDE11A and familial TGCT risk. To validate this novel observation, we sequenced the PDE11A coding region in 259 additional TGCT patients (both familial and sporadic) and 363 controls. We identified 55 PDE11A variants: 20 missense, four splice-site, two nonsense, seven synonymous, and 22 intronic. Ten missense variants were novel; nine occurred in transcript variant 4 and one in transcript variant 3. Five rare mutations (p.F258Y, p.G291R, p.V820M, p.R545X, and p.K568R) were present only in cases and were significantly more common in cases vs controls (P=0.0037). The latter two novel variants were functionally characterized and shown to be functionally inactivating, resulting in reduced PDE activity and increased cAMP levels. In further analysis of this cohort, we focused on white participants only to minimize confounding due to population stratification. This study builds upon our prior reports implicating PDE11A variants in familial TGCT, provides the first independent validation of those findings, extends that work to sporadic testicular cancer, demonstrates that these variants are uncommonly but reproducibly associated with TGCT, and refines our understanding regarding which specific inactivating PDE11A variants are most likely to be associated with TGCT risk.

scholarly journals Gastrointestinal Involvement of Testicular Germ Cell Tumor: A Case Report and Literature Review

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Oluwaseun Shogbesan ◽  
Abdullateef Abdulkareem ◽  
Asad Jehangir ◽  
Sunila Byreddy ◽  
Sharon Swierczynski ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Young Men ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Scrotal Swelling ◽  
Gi Bleed

Testicular germ cell tumors (GCT) are the commonest solid tumors in young men. Typical presentation is with painless scrotal swelling; however, symptoms related to complications or metastasis may be the initial presentation. Gastrointestinal (GI) metastasis is seen in about 5% of patients with germ cell tumors and presentation is commonly with GI bleed. It is important to have GCT as a differential diagnosis of GI bleed in young men presenting with unexplained anemia as direct questioning about scrotal swelling and genital examination when appropriate will guide further investigation and facilitate prompt diagnosis. We present a case of a 26-year-old man with testicular germ cell tumor and severe anemia secondary to extension and perforation of duodenum by retroperitoneal metastasis and a review of the literature on the gastrointestinal manifestations of testicular germ cell tumors.

scholarly journals Benign Neck Metastasis of a Testicular Germ Cell Tumor

2015 ◽  
Vol 100 (1) ◽  
pp. 164-168 ◽  
Author(s):  
Haim Gavriel ◽  
Stephen Kleid
Keyword(s):  
Germ Cell ◽  
Neck Dissection ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Neck Mass ◽  
Testicular Germ Cell ◽  
Chyle Leak ◽  
Neck Metastasis ◽  
Lower Neck

Abstract Germ cell tumors (GCTs) are relatively rare neoplasms considered to be curable malignancies since the introduction of cisplatin. The presence of neck metastasis has been reported, with fewer reports of metastatic mature teratoma. In this study, 3 cases of “benign neck” metastasis in patients with GCT between 1998 and 2010 were reviewed retrospectively. In all 3 cases the presenting clinical sign was a left lower neck mass, leading to the diagnosis of the primary site in the testis. All had surgical salvage following chemotherapy, with benign lesions or mature teratoma in histopathology of the neck mass. Chemotherapy was followed by salvage lower-half neck dissection showing benign features in the neck specimen, even though malignancy was proven histologically in other areas. Only 1 patient had a postoperative chyle leak, which resolved spontaneously after several days. Neck dissection is recommended in those patients because malignancy cannot be excluded.

scholarly journals Combining Hypermethylated RASSF1A Detection Using ddPCR with miR-371a-3p Testing: An Improved Panel of Liquid Biopsy Biomarkers for Testicular Germ Cell Tumor Patients

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5228
Author(s):  
João Lobo ◽  
Lieke M. J. van Zogchel ◽  
Mohammed G. Nuru ◽  
Ad J. M. Gillis ◽  
C. Ellen van der Schoot ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Residual Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Adult Males ◽  
Serum Samples ◽  
Liquid Biopsies ◽  
Testicular Germ Cell

The classical serum tumor markers used routinely in the management of testicular germ cell tumor (TGCT) patients—alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG)—show important limitations. miR-371a-3p is the most recent promising biomarker for TGCTs, but it is not sufficiently informative for detection of teratoma, which is therapeutically relevant. We aimed to test the feasibility of hypermethylated RASSF1A (RASSF1AM) detected in circulating cell-free DNA as a non-invasive diagnostic marker of testicular germ cell tumors, combined with miR-371a-3p. A total of 109 serum samples of patients and 29 sera of healthy young adult males were included, along with representative cell lines and tumor tissue samples. We describe a novel droplet digital polymerase chain reaction (ddPCR) method for quantitatively assessing RASSF1AM in liquid biopsies. Both miR-371a-3p (sensitivity = 85.7%) and RASSF1AM (sensitivity = 86.7%) outperformed the combination of AFP and HCG (sensitivity = 65.5%) for TGCT diagnosis. RASSF1AM detected 88% of teratomas. In this representative cohort, 14 cases were negative for miR-371a-3p, all of which were detected by RASSF1AM, resulting in a combined sensitivity of 100%. We have described a highly sensitive and specific panel of biomarkers for TGCT patients, to be validated in the context of patient follow-up and detection of minimal residual disease.

scholarly journals The Past and Future of Biomarkers in Testicular Germ Cell Tumors

2020 ◽  
Vol 1 (1) ◽  
pp. 77-84
Author(s):  
Aditya Bagrodia ◽  
Siamak Daneshmand ◽  
Liang Cheng ◽  
James Amatruda ◽  
Matthew Murray ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Critical Role ◽  
Elevated Serum ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Next Generation ◽  
Testicular Germ Cell ◽  
Circulating Micrornas ◽  
Serum Tumor Markers

Testicular germ cell tumor (GCT) is the most common malignancy in 18- to 40-year-old men. Unlike most other cancers, GCT is frequently curable even when metastatic. These tumors can be classified histologically into seminoma and non-seminoma, which determines treatment. Therefore, successful treatment requires accurate diagnosis, classification, and monitoring. Serum tumor markers, including lactate dehydrogenase, α-fetoprotein, and β-human chorionic gonadotropin, aid in the classification and staging of GCTs. These markers therefore play a critical role in the decision-making process when managing GCT patients. However, there exist many scenarios in which these markers fail to perform adequately. This is particularly true in the case of seminoma, where only 10% to 15% will have elevated serum tumor markers. Non-specific elevation of these markers is also a common occurrence, complicating the interpretation of borderline positive results, particularly in follow-up. To bridge this gap in performance, next generation biomarkers are being investigated. In this review, we consider the role of conventional serum tumor markers in GCT management and discuss recent advances in the next generation of biomarkers, with a focus on circulating microRNAs. We discuss the value that circulating microRNAs could bring as an addition to currently used markers, as well as potential weaknesses, in GCT management.

scholarly journals COMBINED TREATMENT OF A PATIENT WITH A TESTICULAR GERM CELL TUMOR WITH SIGNS OF MULTIPLE ORGAN FAILURE

2019 ◽  
Vol 6 (3) ◽  
pp. 129-137
Author(s):  
T. V. Ustinova ◽  
L. V. Bolotina ◽  
A. A. Fedenko ◽  
H. S. Gevorgyan ◽  
A. A. Paichadze ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Combined Treatment ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Distant Metastases ◽  
Multiple Organ ◽  
Cell Tumor ◽  
Testicular Germ Cell

Testicular cancer is a rare malignant tumor. In the structure of general cancer incidence, this nosology accounts for about 1–1.5% of cases. Among this pathology, about 90–95% is due to testicular germ cell tumors. Currently, testicular cancer is a potentially treatable solid tumor with a 10-year survival rate of more than 95% upon timely diagnosis and proper treatment. In this regard, early diagnosis and treatment of this pathology is an urgent task today. The article presents a clinical observation of the treatment of a patient with a testicular germ cell tumor. The presented clinical case demonstrates the successful conduct of neoadjuvant chemotherapy and further orchifuniculectomy in the presence of distant metastases namely in case of a non-seminomic form of a testicular germ cell tumor. The approach to treating patients with testicular tumors must be individualized and take into account both the potential gain and the potential risks of the treatment being performed.

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