-
Andrology Jul 2019Testicular germ cell tumors (GCTs) represent the most common malignancy in young men. While GCTs represent a model for curable solid tumors due to exquisite... (Review)
Review
BACKGROUND
Testicular germ cell tumors (GCTs) represent the most common malignancy in young men. While GCTs represent a model for curable solid tumors due to exquisite chemosensitivity, mortality for patients with GCT comprises the most life years lost for non-pediatric malignancies. Given limited options for patients with platinum-resistant disease, improved insight into GCT biology could identify novel therapeutic options for patients with platinum-resistant disease. Recent studies into molecular characteristics of both early stage and advanced germ cell tumors suggest a role for rationally targeted agents and potentially immunotherapy.
RECENT DEVELOPMENTS
Recent GWAS meta-analyses have uncovered additional susceptibility loci for GCT and provide further evidence that GCT risk is polygenic. Chromosome arm level amplifications and reciprocal loss of heterozygosity have been described as significantly enriched in GCT compared to other cancer types. Contemporary analyses confirm ubiquitous gain of isochromosome 12 and mutations in addition to previously described GCT-associated genes such as KIT and KRAS. Alterations within the TP53-MDM2 signal transduction pathway appear to be enriched among patients with platinum-resistant disease. Potentially actionable targets, including alterations in TP53-MDM2, Wnt/β-catenin, PI3K, and MAPK signaling, are present in significant proportions of patients with platinum-resistant disease and may be exploited as therapeutic options. Pre-clinical and early clinical data also suggest a potential role for immunotherapy among patients with GCTs.
CONCLUSION
Molecular characterization of GCT patients may provide biologic rationale for novel treatment options in patients with platinum-resistant disease.
Topics: Chromosome Aberrations; Epigenesis, Genetic; Genetic Predisposition to Disease; Genomics; Humans; Immunotherapy; Male; Mutation; Neoplasms, Germ Cell and Embryonal; Signal Transduction; Testicular Neoplasms
PubMed: 30896089
DOI: 10.1111/andr.12616 -
Psycho-oncology Sep 2022The purpose of this review was to synthesise the literature on the topic of masculinity and testicular cancer (TC) and investigate the relative impact of TC on men's... (Review)
Review
OBJECTIVE
The purpose of this review was to synthesise the literature on the topic of masculinity and testicular cancer (TC) and investigate the relative impact of TC on men's view of their masculinity.
METHODS
Searches were conducted across four databases (MEDline, PsycInfo, CINAHL Plus and Scopus) for articles published before April 2022 that included (1) TC and (2) masculinity. Two researchers independently rated studies for inclusion with a third resolving conflicts. Of the 6464 articles screened, 24 articles (10 quantitative and 14 qualitative) were included in the review. Articles were rated for quality and a narrative synthesis was performed.
RESULTS
Overall, results indicated some men experience a shift in the way they relate to their sense of masculinity following diagnosis and treatment for TC. Being single and without children was related to the experience of negative masculinity-related outcomes, possibly due to a compounding lack of relational support and being unable to conform to protector, provider traditions. Men who described testicle loss as symbolic of their diminished masculinity were also negatively impacted. However, recent, high-quality literature on the topic using standardised masculinity measures was limited.
CONCLUSION
Some men experience a reduced sense of masculinity after TC, however the impact of TC on masculinity remains person dependent. Further research using validated masculinity measures is required to uncover psycho-social variables that may account for whether and how meaning is made between TC and its treatment and any subsequent impact on perceived masculinity. Such factors may better support these men in life beyond cancer.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO. International Prospective Register of Systematic Reviews: CRD42020185649.
Topics: Child; Humans; Male; Masculinity; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms
PubMed: 35789023
DOI: 10.1002/pon.5994 -
Medicina (Kaunas, Lithuania) Jul 2023: The relationship between male infertility (MI) and testicular cancer (TC) is bilateral. On one hand, it is well-established that patients diagnosed with TC have a high... (Review)
Review
: The relationship between male infertility (MI) and testicular cancer (TC) is bilateral. On one hand, it is well-established that patients diagnosed with TC have a high risk of pre- and post-treatment infertility. On the other hand, the risk of developing TC in male infertile patients is not clearly defined. The objective of this review is to analyze the histopathological, etiological, and epidemiological associations between MI and the risk of developing testicular cancer. This review aims to provide further insights and offer a guide for assessing the risk factors for TC in infertile men. : A comprehensive literature search was conducted to identify relevant studies discussing the relationship between MI and the risk of developing TC. : The incidence rates of germ cell neoplasia in situ (GCNIS) appear to be high in infertile men, particularly in those with low sperm counts. Most epidemiological studies have found a statistically significant risk of developing TC among infertile men compared to the general or fertile male populations. The concept of Testicular Dysgenesis Syndrome provides an explanatory model for the common etiology of MI, TC, cryptorchidism, and hypospadias. Clinical findings such as a history of cryptorchidism could increase the risk of developing TC in infertile men. Scrotal ultrasound evaluation for testis lesions and microlithiasis is important in infertile men. Sperm analysis parameters can be useful in assessing the risk of TC among infertile men. In the future, sperm and serum microRNAs (miRNAs) may be utilized for the non-invasive early diagnosis of TC and GCNIS in infertile men. : MI is indeed a risk factor for developing testicular cancer, as demonstrated by various studies. All infertile men should undergo a risk assessment using clinical examination, ultrasound, and semen parameters to evaluate their risk of TC.
Topics: Humans; Male; Testicular Neoplasms; Cryptorchidism; Semen; Infertility, Male
PubMed: 37512119
DOI: 10.3390/medicina59071305 -
Journal of Clinical Oncology : Official... Nov 2021
Topics: Cancer Survivors; Humans; Male; Neoplasms, Germ Cell and Embryonal; Survivorship; Testicular Neoplasms
PubMed: 34591594
DOI: 10.1200/JCO.21.01984 -
Journal of Pediatric Urology Dec 2021The exact correlation of testicular microlithiasis (TM) with benign and malignant conditions remains unknown, especially in the paediatric population. The potential... (Review)
Review
The prognostic value of testicular microlithiasis as an incidental finding for the risk of testicular malignancy in children and the adult population: A systematic review. On behalf of the EAU pediatric urology guidelines panel.
INTRODUCTION
The exact correlation of testicular microlithiasis (TM) with benign and malignant conditions remains unknown, especially in the paediatric population. The potential association of TM with testicular malignancy in adulthood has led to controversy regarding management and follow-up.
OBJECTIVE
To determine the prognostic importance of TM in children in correlation to the risk of testicular malignancy or infertility and compare the differences between the paediatric and adult population.
STUDY DESIGN
We performed a literature review of the Medline, Embase and Cochrane controlled trials databases until November 2020 according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) Statement. Twenty-six publications were included in the analysis.
RESULTS
During the follow-up of 595 children with TM only one patient with TM developed a testicular malignancy during puberty. In the other 594 no testicular malignancy was found, even in the presence of risk factors. In the adult population, an increased risk for testicular malignancy in the presence of TM was found in patients with history of cryptorchidism (6% vs 0%), testicular malignancy (22% vs 2%) or sub/infertility (11-23% vs 1.7%) compared to TM-free. The difference between paediatric and adult population might be explained by the short duration of follow-up, varying between six months and three years. With an average age at inclusion of 10 years and testicular malignancies are expected to develop from puberty on, testicular malignancies might not yet have developed.
CONCLUSION
TM is a common incidental finding that does not seem to be associated with testicular malignancy during childhood, but in the presence of risk factors is associated with testicular malignancy in the adult population. Routine monthly self-examination of the testes is recommended in children with contributing risk factors from puberty onwards. When TM is still present during transition to adulthood a more intensive follow-up could be considered.
Topics: Adult; Calculi; Child; Humans; Incidental Findings; Lithiasis; Male; Prognosis; Testicular Diseases; Testicular Neoplasms; Ultrasonography; Urology
PubMed: 34217588
DOI: 10.1016/j.jpurol.2021.06.013 -
Andrology Jul 2019Determining stage and anticipating prognosis are the two crucial steps after the diagnosis of a germ-cell cancer that both guide subsequent treatment decisions. This... (Review)
Review
Determining stage and anticipating prognosis are the two crucial steps after the diagnosis of a germ-cell cancer that both guide subsequent treatment decisions. This review focuses on metastatic disease, which means germ-cell cancers beyond stage I limited to the testis. In the past, major centers developed separate staging and prognostic classifications for metastatic germ-cell cancer, which heavily impaired communication and comparisons across clinical trials. More recently, the classification system of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has found acceptance worldwide and is currently being updated.
Topics: Humans; Male; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Prognosis; Testicular Neoplasms
PubMed: 30969027
DOI: 10.1111/andr.12615 -
The Journal of Clinical Endocrinology... Nov 2022The purpose of this study is to report development of a malignant testicular germ cell tumor (GCT) in 2 young adult males with familial male-limited precocious puberty... (Review)
Review
OBJECTIVE
The purpose of this study is to report development of a malignant testicular germ cell tumor (GCT) in 2 young adult males with familial male-limited precocious puberty (FMPP) because of LHCGR pathogenic variants in 2 families. Secondarily, to study the possible relation between FMPP and testicular tumors and to investigate whether FMPP might predispose to development of malignant testicular tumors in adulthood a literature review is conducted.
METHODS
Data on 6 cases in 2 families are obtained from the available medical records. In addition, a database search is performed in Cochrane, PubMed, and Embase for studies that report on a possible link between FMPP and testicular tumors.
RESULTS
The characteristics of 6 males with FMPP based on activating LH receptor (LHCGR) germline pathogenic variants are described, as are details of the testicular GCTs. Furthermore, a literature review identified 4 more patients with signs of FMPP and a (precursor of) testicular GCT in adolescence or adulthood (age 15-35 years). Additionally, 12 patients with signs of precocious puberty and, simultaneously, occurrence of a Leydig cell adenoma or Leydig cell hyperplasia are reported.
CONCLUSION
There is a strong suggestion that FMPP might increase the risk of development of testicular GCTs in early adulthood compared with the risk in the general population. Therefore, prolonged patient monitoring from mid-pubertal age onward including instruction for self-examination and periodic testicular ultrasound investigation in patients with a germline LHCGR pathogenic variant might contribute to early detection and thus early treatment of testicular GCT.
Topics: Adolescent; Adult; Humans; Male; Young Adult; Puberty, Precocious; Testicular Neoplasms
PubMed: 36071555
DOI: 10.1210/clinem/dgac516 -
Nature Communications May 2023Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II)...
Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.
Topics: Male; Child; Infant; Female; Young Adult; Humans; Adolescent; Infant, Newborn; Child, Preschool; Adult; Wnt Signaling Pathway; Neoplasms, Germ Cell and Embryonal; Teratoma; Testicular Neoplasms; Genomics
PubMed: 37149691
DOI: 10.1038/s41467-023-38378-9 -
Genes May 2022In Saudi Arabia, colon cancer (CC) is the most prevalent cancer in men and the third most common cancer in women. Rather than being detected through screening programs,...
In Saudi Arabia, colon cancer (CC) is the most prevalent cancer in men and the third most common cancer in women. Rather than being detected through screening programs, most CC cases are diagnosed mainly during clinical exams. Because of the slow growth of CC and its ability to be treated at an early stage, screening for CC can reduce the incidence of death and mortality. Consequently, there is an urgent need to identify a potential new cancer-specific biomarker for detecting early illness. Much research has been conducted on distinct antigen classes as potential new cancer-specific biomarkers for the early identification of malignancy. The cancer-testis antigens (CTAs) are one such category of antigens, with protein presence largely normally confined to human germ line cells in the testis and aberrantly produced in some cancer cells. CTAs are potentially valuable for use as cancer biomarkers and in cancer therapeutics due to their distinctive expression pattern. The aim of this current study was to identify potential cancer-testis (CT) gene biomarkers in Saudi Arabian CC patients. In this study, a total of 20 matching CC and normal colon (NC) tissues were obtained from the Saudi population. Any genes that showed expression in CC tissues but not in matching NC tissues were subsequently verified for mRNA expression in eight breast and eight leukemia malignancies using RT-PCR to determine the specificity of any CC biomarkers. and genes were expressed in varying numbers of CC tissues compared to no measurable expressions in all NC tissue specimens, making these genes suitable potential candidates for CC markers. The most frequently expressed CT genes in CC patients were (35%) and (35%), followed by (25%), (20%), (15%), and (5%). The gene shows a weak RT-PCR product in 25% of breast cancer (BC) patients but not in leukemia patients. The gene appears to display expression in all leukemia patients but not in the BC patients. expression was also observed in 50% of leukemia samples but not in the BC samples. More experiments at the protein level and with a larger cohort of patients are required to evaluate this finding.
Topics: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; Breast Neoplasms; Colonic Neoplasms; Female; Genetic Markers; Humans; Leukemia; Male; Saudi Arabia; Testicular Neoplasms
PubMed: 35627192
DOI: 10.3390/genes13050807 -
International Journal of Molecular... Jan 2021Testicular germ cell tumors (TGCTs) are the leading form of solid cancer and death affecting males between the ages of 20 and 40. Today, their surgical resection and... (Review)
Review
Testicular germ cell tumors (TGCTs) are the leading form of solid cancer and death affecting males between the ages of 20 and 40. Today, their surgical resection and chemotherapy are the treatments of first choice, even if sometimes this is not enough to save the lives of patients with TGCT. As seen for several tumors, the deregulation of microRNAs (miRNAs) is also a key feature in TGCTs. miRNAs are small molecules of RNA with biological activity that are released into biological fluids by testicular cancer cells. Their presence, therefore, can be detected and monitored by considering miRNAs as diagnostic and prognostic markers for TGCTs. The purpose of this review is to collect all the studies executed on miRNAs that have a potential role as biomarkers for testicular tumors.
Topics: Adult; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Liquid Biopsy; Male; MicroRNAs; Neoplasms, Germ Cell and Embryonal; Prognosis; Testicular Neoplasms; Testis; Young Adult
PubMed: 33573132
DOI: 10.3390/ijms22031380