Testicular germ cell tumors type 2 have high RNA expression of / 亚洲男科学杂志(英文版)

This study analyzed RNA expression of genes for three serum tumor markers, alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH), in patients with testicular germ cell tumors (TGCT) type 2. The gene AFP encodes AFP, the gene for chorionic gonadotropin beta polypeptide 5 (CGB5) encodes a major part of the specific beta subunit of hCG, and the genes for LDH subunit A (LDHA), LDH subunit B (LDHB), and LDH subunit C (LDHC) encode three different subunits of LDH. LDHB encodes the LDHB subunit present as a tetramer in LDH isoenzyme 1 (LDH-1). We examined three datasets with 203 samples of normal testis tissue (NT) and TGCT type 2. Yolk sac tumor (YST) expressed RNA of AFP fourteen thousand times higher than seminoma (SE), embryonal carcinoma (EC), and teratoma (TER) combined (P = 0.00015). In the second microarray, choriocarcinoma (CC) expressed RNA of CGB5 ten times higher than other histologic types of TGCT combined. EC expressed RNA of LDHB twice higher than SE, YST and TER combined (P = 0.000041). EC expressed RNA of LDHB higher than that YST expressed RNA of AFP and that CC expressed RNA of CGB5. In conclusion, TGCT type 2 expressed RNA of LDHB markedly higher than the RNA of 23 other candidate genes for TGCT type 2.

Characterization of progression-related alternative splicing events in testicular germ cell tumors / 亚洲男科学杂志(英文版)

Accumulating evidence supports the significance of aberrant alternative splicing (AS) events in cancer; however, genome-wide profiling of progression-free survival (PFS)-related AS events in testicular germ cell tumors (TGCT) has not been reported. Here, we analyzed high-throughput RNA-sequencing data and percent-spliced-in values for 150 patients with TGCT. Using univariate and multivariate Cox regression analysis and a least absolute shrinkage and selection operator method, we identified the top 15 AS events most closely associated with disease progression. A risk-associated AS score (ASS) for the 15 AS events was calculated for each patient. ASS, pathological stage, and T stage were significantly associated with disease progression by univariate analysis, but only ASS and pathological stage remained significant by multivariate analysis. The ability of these variables to predict 5-year progression was assessed using receiver operating characteristic curve analysis. ASS had stronger predictive value than a combination of age, pathological stage, and T stage (area under the curve = 0.899 and 0.715, respectively). Furthermore, Kaplan-Meier analysis of patients with low and high ASS demonstrated that high ASS was associated with significantly worse PFS than low ASS (P = 1.46 × 10

Effects of testicular dysgenesis syndrome components on testicular germ cell tumor prognosis and oncological outcomes

ABSTRACT Purpose: To evaluate whether components of Testicular Dysgenesis Syndrome (TDS) affect testicular germ cell tumor (TGCT) prognosis and oncological outcomes. According to the hypothesis called TDS; undescended testis, hypospadias, testicular cancer and spermatogenic disorders share the same risk factors and have a combined fetal origin. Materials and Methods: We retrospectively evaluated the stages and oncological outcomes of 69 patients who underwent radical orchiectomy between January 2010 and December 2014 due to TGCT in our department. The presence of undescended testis, hypospadias and semen parameters disorders were recorded according to anamnesis of patients. Results: Among 69 patients with TGCT, only 16 (23.1%) had TDS. Significantly higher rate of TDS (36.1% vs. 9.1%) was observed at the advanced stages of TGCT(p=0.008). In the TDS group, the rates of local recurrence (50% vs. 11.3%, p<0.001), distant metastasis (93.6% vs. 3.8%, p<0.001) and cancer-spesific mortality (87.5% vs. 3.8%, p<0.001) were found significantly higher than those without TDS. The predicted time for recurrence-free survival (13.70±5.13 vs. 100.96±2.83 months, p<0.001) metastasis-free survival (13.12±4.21 vs. 102.79±2.21 months, p <0.001) and cancer-specific survival (13.68±5.38 vs. 102.80±2.19 months, p<0.001) were also statistically lower in this group. Conclusions: According to our preliminary results, there is an apparent relationship between TDS and tumor prognosis. Even if the components of TDS alone did not contain poor prognostic features for TGCT, the presence of TDS was found as the most important independent predictive factor for oncological outcomes in both seminomas and nonseminomas as well as all patients with TGCT.

Trends in cancer incidence in Uruguay: 2002 -2015 / Tendencias de la incidencia de cáncer en Uruguay: 2002-2015

Abstract Background: Uruguay is the south American country which has the highest cancer incidence and mortality rates. The National Cancer Registry collects data on cancer cases nationwide since 1989 and has reached high quality standards in the last decades. This is the first report on incidence trends. Methods: Data from the National Cancer Registry of all new cases of invasive cancer from twelve sites diagnosed in 2002-2015 was analyzed. Age-standardized rates were calculated. Trends of incidence rates were analyzed using joinpoint regression models. Results: For both, men and women, incidence rates trends for all cancer sites, colo-rectal and bladder cancer remained stable. Esophageal and gastric cancers descended while thyroid and kidney cancer incidence increased. In men lung cancer decreased; testicular cancer increased, and prostate cancer increased at the beginning of the period and decreased in the final years. In women, lung cancer increased, breast cancer remained stable and cervical cancer presented a significant decline from 2005 to 2010 and reached a plateau since then. Conclusion: Cancer incidence dynamics are complex and affected not only by Public Health policies such as tobacco control, vaccination and screening programs, but also by environmental and life style changes and the attitude of the medical community towards the application of diagnostic and therapeutic tools. The aim of this paper is to analyze cancer incidence time trends in the country and provide possible explanations to them.

Resumen Introducción: Uruguay es el país de Sudamerica que tiene las mayores tasas de incidencia y mortalidad por cáncer. El Registro Nacional de Cáncer recoge los datos de cáncer de todo el país desde 1989 y en las últimas décadas ha alcanzado los más altos estándares de calidad. Este es el primer reporte de tendencias de incidencia de cáncer de Uruguay. Métodos: Se analizaron los datos de todos los casos de cáncer invasivo diagnosticados entre 2002 y 2015 incluidos en el Registro Nacional de Cáncer y los de once topografías en particular. Se calcularon las tasas de incidencia estandarizada y se analizaron las tendencias utilizando los modelos de regresión de Joinpoint. Resultados: Las tasas de incidencia de cáncer colorrectal, vejiga y todos los sitios reunidos se mantuvieron estables tanto en hombres como en mujeres. La tasa de incidencia de cáncer de estómago y esófago disminuyeron mientras que las de tiroides y riñón aumentaron. En los hombres, el cáncer de pulmón disminuyó, el cáncer de testículo aumentó y el de próstata aumentó en un lapso inicial y decreció en los últimos años. En las mujeres el cáncer de pulmón aumentó y el de mama se mantuvo estable mientras que el cáncer de cérvix presentó un descenso significativo entre 2005 y 2010 alcanzando una meseta desde entonces. Conclusión: La dinámica de la incidencia de cáncer es compleja y está afectada no sólo por las políticas de Salud Pública como las campañas de control de tabaco, vacunación y programas de tamizaje sino por los cambios ambientales y de los estilos de vida y la actitud de los médicos respecto a la aplicación de técnicas diagnósticas y terapéuticas. En este trabajo se analizan las tendencias de incidencia en el país y se plantean posibles explicaciones para los cambios.

Testicular mixed germ cell tumor presenting with seizure as the initial symptom: a case report and literature review

Abstract Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy.

Correlation of 41 loci of single nucleotide polymorphisms with testicular germ cell tumor / 中华男科学杂志

<p><b>Objective</b>To identify genetic susceptibility genes and the loci of their single nucleotide polymorphisms (SNPs) in patients with testicular germ cell tumor (TGCT) and provide some new ideas for the prediction, diagnosis and treatment of TGCT.</p><p><b>METHODS</b>We identified 41 SNP loci of TGCT-related genetic susceptibility genes from the literature published abroad. Using the iMLDRTM genotyping technique, we examined the SNP loci of the genetic susceptibility genes in the blood samples from 76 TGCT patients (aged 16－68 years) and 148 healthy men (aged 22－61 years) in China and analyzed their correlation with TGCT.</p><p><b>RESULTS</b>In China, TGCT was found to be correlated with the SNP loci rs2978381, rs10146204, rs12435857 and rs1256063 of the ESR2 gene, rs9397080 of the ESR1 gene, rs11202586 of the PTEN gene, rs2606345 and rs4646903 of the CYP1A1 gene, and rs1456432 of the CYP19A1 gene.</p><p><b>CONCLUSIONS</b>The results of our study indicated some difference in the positive SNP loci of the TGCT patients between Chinese and foreign cohorts as well as in different groups in China.</p>

Antioxidant enzyme profile and lipid peroxidation products in semen samples of testicular germ cell tumor patients submitted to orchiectomy

ABSTRACT Purpose To determine enzymatic antioxidant and lipid peroxidation levels in seminal plasma of patients orchiectomized for testicular tumors. Materials and Methods The study included 52 patients: 26 control men and 26 orchiectomized patients for testicular tumor, of which 12 men had seminoma tumor and 14 men non-seminoma tumor. After semen analysis performed according to the WHO guidelines, an aliquot of semen was centrifuged and the seminal plasma was collected. Lipid peroxidation was performed by thiobarbituric acid reactive substances (TBARS) assay and antioxidant profile was assessed by analyzing catalase, glutathione peroxidase (GPx) and superoxide anion (SOD) activities using colorimetric assays with a standard spectrophotometer. Data were tested for normality and compared using one-way ANOVA (p<0.05). Results Seminoma and non-seminoma groups presented lower sperm concentration and morphology when compared to control group (p=0.0001). Both study groups (seminoma and non-seminoma) presented higher TBARS levels when compared to control group (p=0.0000013). No differences were observed for SOD (p=0.646) andGPx (p=0.328). It was not possible to access the enzymatic activity of catalase in any group. Conclusion Patients with testicular tumor present increased semen oxidative stress, but no differences were observed in antioxidant levels, even after orchiectomy. This indicates that most likely an increased generation of oxidative products takes place in these patients.

Clinicopathologic and Oncological Outcomes in Korean Men With Advanced Metastatic Testicular Cancer Undergoing Postchemotherapeutic Retroperitoneal Lymph Node Dissection

PURPOSE: To evaluate the clinicopathologic and oncological outcomes of advanced metastatic testicular cancer in Korean men who underwent retroperitoneal lymph node dissection (RPLND) following chemotherapy. MATERIALS AND METHODS: Data of 26 patients with testicular cancer who underwent RPLND after chemotherapy at 2 hospitals in Korea between September 2004 and June 2016 were retrospectively analyzed. Clinical and histopathological variables such as stage of the testicular cancer, age of the patients during surgery, size of the retroperitoneal lymph nodes (RPLNs), histopathological results, duration and complications related to the surgery, cancer recurrence, and mortality were analyzed. RESULTS: During testicular surgery, the T stage was pT1, pT2, and pT3 in 50% (n=13), 26.9% (n=7), and 15.3% (n=4) of the patients, respectively. Mixed germ cell tumor was the most common finding, seen in 73.1% (n=19) of patients. The indications for RPLND were residual lymph nodes after chemotherapy, 84.6% (n=22); and disease progression and remission, 7.7% (n=2). Pathological analysis revealed viable tumors in 19.2% of patients (n=5), necrotic/fibrotic tissue in 42.3% (n=11), and teratoma in 34.6% (n=9). Intraoperative and postoperative complications occurred in 23.1% (n=6) and 19.2% of patients (n=5). The median duration of follow-up was 27.5 months (interquartile range, 1.3–108.2 months); 11.5% (n=3) patients had recurrence, and 3.8% (n=1) died of progressive metastatic testicular cancer. CONCLUSIONS: Viable germ cell tumors were present in 19.2% of patients with testicular cancer who underwent RPLND after chemotherapy. This is the first study of its kind in the Korean population.

Diagnostic value of immunohistochemistry and FISH for chromosome 12p in type Ⅱ testicular germ cell tumors / 中华男科学杂志

<p><b>Objective</b>To study the pathological morphology, immunohistochemical characteristics, and molecular changes of type Ⅱ testicular germ cell tumors (TGCT) and investigate the possible value of immunohistochemistry and fluorescence in situ hybridization (FISH) in the diagnosis of TGCT.</p><p><b>METHODS</b>We collected for this study 97 cases of TGCT, including 75 cases of seminoma, 17 cases of embryonal carcinoma, 11 cases of yolk sac tumor, 16 cases of mature teratoma, 3 cases of immature teratoma, and 1 case of epidermoid cyst, in which normal testicular tissue was found in 20 and non-TGCT in 6. We detected the expressions of different antibodies in various subtypes of TGCT by immunohistochemistry and determined the rate of chromosome 12p abnormality using FISH.</p><p><b>RESULTS</b>The immunophenotypes varied with different subtypes of TGCT. SALL4 and PLAP exhibited high sensitivity in all histological subtypes. CD117 and OCT4 showed strongly positive expressions in invasive seminoma and germ cell neoplasia in situ (GCNIS) but not in normal seminiferous tubules. GPC3 was significantly expressed in the yolk sac tumor, superior to GATA3 and AFP in both range and intensity. CKpan, OCT4, and CD30 were extensively expressed in embryonal carcinoma, while HCG expressed in choriocarcinoma. The positivity rate of isochromosome 12p and 12p amplification in TGCT was 96.7% (29/30).</p><p><b>CONCLUSIONS</b>The majority of TGCT can be diagnosed by histological observation, but immunohistochemical staining is crucial for more accurate subtypes and valuable for selection of individualized treatment options and evaluation of prognosis. Chromosome 12p abnormality is a specific molecular alteration in type Ⅱ TGCT, which is useful for ruling out other lesions.</p>

Overview of Pediatric Testicular Tumors in Korea

Prepubertal testicular tumors are rare compared with postpubertal testicular tumors. The incidence of prepubertal testicular tumors peaks at 2 years of age, tapers off after 4 years of age, and then begins to rise again at puberty. Prepubertal and postpubertal testicular tumors show many differences, including the typical tumor histology, molecular biological differences, and the malignant potential of tumors at different ages. Pediatric testicular tumors are classified as benign or malignant on the basis of their clinical behavior and histologically are divided into germ cell and gonadal stromal (nongerm cell) tumors. Many histological and biological studies have further confirmed the distinct nature of prepubertal and postpubertal testicular tumors. These differences have led to various management strategies for prepubertal and postpubertal tumors. Because overall about 75% of prepubertal testicular tumors are benign, a testis-sparing approach is becoming more common in children. Orchiectomy and observation with very selective use of chemotherapy has become the standard approach when a malignant tumor is identified. Retroperitoneal lymph node dissection and radiation therapy play very limited roles.

Linfadenectomía lumboaórtica laparoscópica para cáncer testicular no seminomatoso estadio clínico I / Laparoscopic lumbo-aortic lymph-node dissection in clinical stage i non-seminomatous testicular germ-cell tumors

Reportar la morbilidad y resultados oncológicos de la Linfadenectomía Lumboaórtica por vía laparoscópica (LLA lap) en pacientes portadores de tumor de células germinales no seminomatoso (TCGNS) estadio I, operados en el Hospital Ramón Barros Luco Trudeau. Pacientes y Métodos: Entre octubre de 2005 y agosto de 2008, 29 pacientes con TCGNS estadio I, fueron sometidos a LLA lap. No se realizó selección de pacientes en relación a los hallazgos anatomopatológicos o a la presencia de factores de riesgo. La Linfadenectomía retroperitoneal fue realizada por el mismo cirujano, respetando los límites descritos por Weissbach y Boedefeld. Resultados: De los 29 pacientes operados, el procedimiento fue completado en su totalidad por vía laparoscópica. La pérdida sanguínea promedio fue de 27,7 cc (5–250). No fue necesaria tranfusión sanguínea. El tiempo operatorio promedio fue de 170 min (150–240). El número de ganglios resecados promedio fue de 12,8 (4–25). El tiempo de hospitalización fue de 2 días. Se registró una complicación vascular intraoperatoria, que se manejo satisfactoriamente sin necesidad de conversión. Se preservó la eyaculación anterograda en la totalidad de los pacientes. Cuatro pacientes (13,8 por ciento) tuvieron estadio patológico IIa y recibieron quimioterapia adyuvante con Cisplatino, Etopósido y Bleomicina. Durante un periodo de seguimiento promedio de 19 meses (2-36) ninguno de los pacientes ha presentado recidiva. Conclusión: La Linfadenectomía Lumboaórtica por vía Laparoscópica ha demostrado ser una excelente herramienta de estadificación, la cual ofrece una alternativa mínimamente invasiva a la cirugía convencional abierta. Los resultados de la serie, durante el periodo de seguimiento, demuestran su equivalencia oncológica a la cirugía abierta, sumándose los beneficios de la técnica laparoscópica que incluyen, una menor morbilidad y una mejoría tanto en la visualización intraoperatoria, resultado estético como en la calidad de vida del paciente.

To report the morbidity and oncological results of laparoscopic lumbo-aortic lymph-node dissection (LLA lap) in clinical stage I non-seminomatous testicular germ cell tumors (TCGNS), operated at the Hospital Ramón Barros Luco Trudeau.Patients and Methods: Between October 2005 and August 2008, 29 patients with stage I TCGNS, underwent LLA lap. No patient selection was made in relation to the pathological findings or the presence of risk factors. Retroperitoneal lymphadenectomy was performed by the same surgeon within the limits described by Weissbach and Boedefeld. Results: The procedure was completed in its entirety with laparoscopic procedure. The average blood loss was 27.7 cc (5-250). There was no blood tranfusion. The average operative time was 170 min (150-240). The average number of lymph nodes resected was 12.8 (4-25). The hospitalization time was 2 days. There was an intraoperative vascular complication, which satisfactorily manage without conversion to open surgery. Antegrade ejaculation was preserved in all patients. 4 patients (13.8 percent) had pathological stage II received adjuvant chemotherapy with cisplatin, etoposide and bleomycin. During an average follow-up period of 19 months (2-36) none of the patients presented recurrence. Conclusion: The laparoscopic lumbo-aortic lymph-node dissection has proven to be an excellent staging tool, which offers a minimally invasive alternative to conventional open surgery. The results of the series during the follow-up period, demonstrate oncological equivalence to open surgery, adding the benefits of laparoscopic technique including a lower morbidity and an improvement in intraoperative visualization, aesthetic result and the quality of patient’s life.

Quantitation of spermatogenesis by DNA flow cytometry: Comparative study among six species of mammals.

Suspensions of testicular germ cells from six species of mammals were prepared and stained for the DNA content with a fluorochrome (ethidium bromide) adopting a common technique and subjected to DNA flow cytometry. While uniform staining of the germ cells of the mouse, hamster, rat and monkey could be obtained by treating with 0·5% pepsin for 60 min followed by staining with ethidium bromide for 30 min, that of the guinea pig and rabbit required for optimal staining pepsinization for 90 min and treatment with ethidium bromide for 60 min. The procedure adopted here provided a uniform recovery of over 80% of germ cells with each one of the species tested and the cell population distributed itself according to the DNA content (expressed as C values) into 5 major classes– spermatogonia (2C), cells in S-phase, primary spermatocytes (4C), round spermatids (1C), and elongating/elongated spermatids (HC). Comparison of the DNA distribution pattern of the germ cell populations between species revealed little variation in the relative quantities of cells with 2C (8–11%), S-phase (6–9%), and 4C (6–9%) amount of DNA. Though the spermatid cell populations exhibited variations (1C:31–46%, HCl:7– 20% and and HC2:11–25%) they represented the bulk of germ cells (70–80%). The overall conversion of 2C to 1C (1C:2C ratio) and meiotic transformation of 4C cells to 1C (1C:4C ratio) kinetics were relatively constant between the species studied. The present study clearly demonstrates that DNA flow cytometry can be adopted with ease and assurance to quantify germ cell transformation and as such spermatogenesis by analysing a large number of samples with consistency both within and across the species barrier. Any variation from the norms in germ cell proportions observed following treatment, for e.g. hormonal stimulation or deprivation can then be ascribed due to a specific effect of the hormone/drug on single/multiple steps in germ cell transformation.

Expression and significance of LRP and GST-?in the testis germ cell tumor / 重庆医科大学学报

Objective: To investigate the expression of LRP,GST-?in the testicular germ cell tumor and evaluate their role in multidrug resistance of the testicular germ cell tumor.Methods: 41 samples of germ cell tumor without chemotherapy were analyzed immunohistochemically.Results: The total positive percentage of LRP in the testicular germ cell tumor was 41.5%,the frequence of LRP expression in Ⅰ stage,Ⅱ+Ⅲ stage,seminoma and non-seminoma germ cell tumor was 23.1%,73.3%,40.0% and 45.5% respectively.There was significant difference of the LRP expression between I stage and Ⅱ+Ⅲ stage in the testis germ cell tumor(P0.05).Conclusion: The expression of LRP was correlational with the clinical stage of the testicular germ cell tumor,and LRP expression may be an important prediction of patients with testicular germ cell tumor.【