RESUMEN
SummaryWe previously demonstrated that among various histological types of human testicular germinal cell tumors (GCTs), embryonal carcinoma (EC) preferentially expresses low-sulfated keratan sulfate (KS) consisting of repeating N-acetyllactosamine (LacNAc) disaccharide units composed of galactose and 6-O-sulfated N-acetylglucosamine (GlcNAc), which is recognized by the R-10G antibody. Recently, we generated another anti-low-sulfated KS monoclonal antibody, 294-1B1. Immunohistochemical analysis of testicular GCTs (n=83) revealed that the low-sulfated KS recognized by 294-1B1 is also preferentially expressed in EC but minimally in other GCT histological types. Moreover, immunolabeling with R-10G and 294-1B1 antibodies was resistant to peptide-N-glycosidase F digestion, and EC was not stained with the MECA-79 antibody, indicating that low-sulfated KS expressed in EC contains mucin-type core 2 O-glycans carrying GlcNAc-6-O-sulfated oligo-LacNAc. Double immunofluorescence staining showed that R-10G and 294-1B1 antibody signals colocalized with those for podocalyxin (PODXL). Furthermore, western blot analysis of recombinant human PODXLâ¢IgG fusion proteins secreted from low-sulfated KS-expressing human embryonic kidney 293T cells revealed that PODXL functions as a core protein for low-sulfated KS. Taken together, these findings strongly suggest that the PODXL glycoform decorated with low-sulfated KS is preferentially expressed in human testicular EC and may therefore serve as a diagnostic marker for this malignancy.
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Carcinoma Embrionario , Sulfato de Queratano , Sialoglicoproteínas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Neoplasias Testiculares/diagnóstico , Sialoglicoproteínas/análisis , Sialoglicoproteínas/metabolismo , Carcinoma Embrionario/patología , Carcinoma Embrionario/metabolismo , Sulfato de Queratano/metabolismo , Sulfato de Queratano/análisis , Inmunohistoquímica , Línea Celular Tumoral , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/diagnósticoRESUMEN
BACKGROUND: Embryonal carcinoma is a rare tissue type in germ cell tumors. According to our literature review, metastatic embryonal carcinoma misdiagnosed as lymphoma because of its high similarity to lymphoma is extremely rare and has not been reported yet. CASE PRESENTATION: A 46-year-old middle adulthood male presented with unexplained fever, night sweats, abdominal distension for 3 months, and weight loss of around 7kg during almost 6 months, which is extremely similar to lymphoma from the clinical features and imaging examinations. After a clear diagnosis, the case not only obtained the opportunity of surgery but was also exempted from radiotherapy. The treatment effect was good. We report a case of rare metastatic embryonal carcinoma, which can provide insight into the diagnosis and treatment of embryonal carcinoma. CONCLUSION: Metastatic embryonal carcinoma of abdominal lymph nodes can be highly similar to lymphoma; the diagnosis can only be based on clinical manifestations and imaging examination but also combined with patient history, tumor markers and biochemical examination. However, the final diagnosis depends on pathological biopsy.
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Carcinoma Embrionario , Linfoma , Humanos , Masculino , Persona de Mediana Edad , Linfoma/diagnóstico por imagen , Carcinoma Embrionario/patología , Carcinoma Embrionario/diagnóstico por imagen , Diagnóstico Diferencial , Metástasis Linfática/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The aims of the present study were to investigate the global changes on proteome of human testicular embryonal carcinoma NT2/D1 cells treated with 17ß-estradiol (E2), and the effects of this hormone on migration, invasion, and colony formation of these cells. A quantitative proteomic analysis identified the presence of 1230 proteins in both E2-treated and control cells. The analysis revealed 75 differentially abundant proteins (DAPs), out of which 43 proteins displayed a higher abundance and, 30 proteins showed a lower abundance in E2-treated NT2/D1 cancer cells. Functional analysis using IPA highlighted some activation processes such as migration, invasion, metastasis, and tumor growth. Interestingly, the treatment with E2 and ERß-selective agonist DPN increased the migration of NT2/D1 cells. On the other hand, ERα-selective agonist PPT did not modify cell migration, indicating that ERß is the upstream receptor involved in this process. The activation of ERß increased the invasion and anchorageindependent growth of NT2/D1 cells more intensely than ERα. ERα and ERß may play overlapping roles on invasion and colony formation of these cells. Further studies are required to clarify the mechanism underlying these effects. The molecular mechanisms revealed by proteomic and functional studies might also guide the development of potential targets for a better understanding of the biology of these cells and novel treatments for non-seminoma in the future.
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Carcinoma Embrionario , Receptores de Estrógenos , Humanos , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Proteómica , Estradiol/farmacologíaRESUMEN
Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Carcinoma Embrionario/metabolismo , Carcinoma Embrionario/patología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismoRESUMEN
Testicular embryonal carcinoma is a type of nonseminomatous germ cell tumor (NSGCT) that commonly presents with scrotal swelling due to testicular mass. About half of patients with NSGCTs will present with metastases at initial diagnosis. Rarely, testicular embryonal carcinoma can present primarily in the mediastinum. Treatment is well-studied and effective: chemotherapy with bleomycin, etoposide, and cisplatin. Post-chemotherapy retroperitoneal lymph node dissection (RPLND) is common adjuvant therapy. In this report we present a case of testicular embryonal carcinoma in a 32-year-old Caucasian man. The rarity of the case resides in its presentation: supraclavicular lymphadenopathy and no testicular mass on palpation or scrotal ultrasound.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Adulto , Mediastino , Carcinoma Embrionario/diagnóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/terapia , EtopósidoRESUMEN
Thus far, several monoclonal antibodies directed against cell-surface carbohydrate antigens have been generated. Among them, R-10G reportedly reacts selectively with human embryonic stem and induced pluripotent stem cells, but not with embryonal carcinoma (EC) cells. However, EC cells derived from patients' EC tumors may exhibit varying levels of R-10G-reactive antigen expression. Thus, we asked whether human EC tissues or germ cell tumor (GCT) tissues other than EC express R-10G-reactive antigen. To do so, we quantitatively analyzed R-10G-reactive antigen expression in 83 testicular GCT surgical specimens containing a total of 125 various GCT components. Accordingly, in all EC components examined, the EC cell plasma membrane was immunolabeled with R-10G, while most seminoma components were R-10G-negative. In non-seminomatous GCT (NSGCT) other than EC (non-EC NSGCT), R-10G-reactive antigen expression was variable, but signal distribution was focal, and the average intensity was weaker than that seen in EC. The percentages of R-10G-positive cells in these three groups varied with high statistical significance (p<0.001 for all combinations). These findings indicate that the R-10G-reactive antigen is preferentially expressed in human testicular EC tissues and, thus, could be used as a diagnostic marker for this malignancy.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Biomarcadores de Tumor , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/metabolismo , Anticuerpos MonoclonalesRESUMEN
AIMS: Testicular germ cell tumours are the most common solid malignancies in young men of age 14-44 years. It is generally accepted that both seminomas and non-seminomas arise from a common precursor, the germ cell neoplasia in-situ, which itself is the result of a defective (primordial) germ cell development. The stem cell-like population of the non-seminomas, the embryonal carcinoma, is capable of the differentiation of all three germ layers (teratomas) and extra-embryonic tissues (yolk-sac tumours, choriocarcioma) into cells. In contrast, seminomas are thought to have a limited differentiation potential. Nevertheless, several studies have highlighted their ability to undergo reprogramming to an embryonal carcinoma or differentiation into other non-seminomatous entities. Here, we demonstrate that in approximately 5% of seminomas, the yolk-sac tumour driver gene FOXA2 is detectable at the protein level, indicative of an occult yolk-sac tumour subpopulation that putatively arose from seminoma cells, as the presence of other GCT entities could be excluded. The presence of these subpopulations might render the tumour more aggressive and argue for an adjustment of the therapeutic concept. We used our data to update the model of germ cell tumour pathogenesis, especially regarding the developmental potential of seminomas. Additionally, we suggest to include detection of FOXA2 into standard routine diagnosis of seminomas.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Seminoma/patología , Neoplasias Testiculares/patología , Diferenciación Celular , Factor Nuclear 3-beta del Hepatocito/genéticaRESUMEN
INTRODUCTION: The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant mediastinal germ cell tumors (MMGCT). METHODS: Data on the demographics, treatment, and survival outcomes of children and adolescents with MMGCT from January 1, 2000 to December 31, 2018 were obtained. To compare survival curves, the log-rank test was employed. The generation of survival curves based on different parameters was done using Kaplan-Meier estimations. Cox proportional hazards regression was performed to determine the variables linked to disease-specific survival. RESULTS: The selection criteria were met by 152 MMGCT patients, 130 of whom were male. Fifty three cases of mixed germ cell tumors (GCTs), 41 cases of malignant teratomas, 26 cases of yolk sac tumors, 14 cases of seminoma, 13 cases of choriocarcinomas, and five cases of embryonal carcinoma were reported. Overall survival at 3 and 5 y for all patients was 63.1% and 61.2%, respectively. Malignant teratoma, yolk sac tumors, and mixed GCTs in children and adolescents had comparable survival rates, while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Embryonal carcinoma, malignant teratoma, mixed GCTs, and choriocarcinoma were found as risk factors by multivariate Cox proportional hazards analysis. In contrast, surgery and younger age were protective factors. However, chemotherapy alone showed no survival benefits. CONCLUSIONS: Our population-based evidence showed that MMGCT had worse prognosis in older children and adolescents. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery can prolong survival time. Chemotherapy and radiotherapy were not associated with improved prognosis.
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Carcinoma Embrionario , Coriocarcinoma , Tumor del Seno Endodérmico , Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Teratoma , Neoplasias Testiculares , Embarazo , Femenino , Humanos , Masculino , Niño , Adolescente , Carcinoma Embrionario/patología , Tumor del Seno Endodérmico/patología , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/terapia , Teratoma/epidemiología , Teratoma/terapia , Teratoma/patología , Neoplasias del Mediastino/epidemiología , Neoplasias del Mediastino/terapia , Neoplasias Testiculares/patologíaRESUMEN
Background and Objectives: The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database. Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality. Results: Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%; p < 0.01) and stage II (0.5 vs. 3.4%, p < 0.01), but not in stage I (0.9 vs. 1.6%, p = 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71, p = 0.01) and stage II (hazard ratio 0.11, p < 0.01). Conclusions: Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Carcinoma Embrionario/patología , Factores de RiesgoRESUMEN
In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/POU5F1, SOX17, KLF4, and MYC, and embryonal carcinoma (EC) has four upregulated genes, OCT4/POU5F1, SOX2, LIN28, and NANOG. The EC panel can reprogram cells into iPSC, and both iPSC and EC can differentiate into teratoma. This review summarizes the literature on epigenetic regulation of the genes. Epigenetic mechanisms, such as methylations of cytosines on the DNA string and methylations and acetylations of histone 3 lysines, regulate expression of these driver genes between the TGCT subtypes. In TGCT, the driver genes contribute to well-known clinical characteristics and the driver genes are also important for aggressive subtypes of many other malignancies. In conclusion, epigenetic regulation of the driver genes are important for TGCT and for oncology in general.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Epigénesis Genética , Neoplasias Testiculares/genética , Neoplasias de Células Germinales y Embrionarias/genética , Carcinoma Embrionario/genética , Carcinogénesis/genética , Transformación Celular Neoplásica/genéticaRESUMEN
BACKGROUND: Lymphovascular invasion (LVI) is a relevant prognostic factor in germ cell tumors of the testis (GCTT), and it is included in the pT stage. However, its detection on hematoxylin and eosin (H&E) slides is very challenging, and previous studies reported fair to moderate inter-observer agreement among dedicated uropathologists. In the present study, we tested H&E and a recently developed in-house double staining for OCT4/CD34 to detect LVI in GCTT. METHODS: Nine authors [5 non-uropathologists and 4 uropathologists] independently evaluated 34 consecutive and retrospectively enrolled cases of GCTT. We assessed the inter-observer agreement (Fleiss's Kappa) with both H&E and OCT4/CD34. Besides, we compared the consensus diagnosis on both H&E and OCT4/CD34-stained sections with the original diagnosis to evaluate the pT re-staging (McNemar test) and identify the sources of disagreement. RESULTS: The inter-observer agreement among uropathologists plus non-uropathologists was fair with both H&E (KF=0.398; p < 0.001) and OCT4/CD34 (KF=0.312; p < 0.001). OCT4/CD34 (KF=0.290; p < 0.001) slightly reduces the inter-observer agreement compared to H&E (KF=0.321; p < 0.001) for non-uropathologists; in contrast, OCT4/CD34 (KF=0.293; p < 0.001) significantly reduces the inter-observer agreement compared to H&E (KF=0.529; p < 0.001) for uropathologists, changing it from moderate to fair. Consensus diagnosis with H&E modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.070), with pT re-staging in 2/34 (5.9 %) cases (p: 0.500). Consensus diagnosis with OCT4/CD34 modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.289), with pT re-staging in 3/34 (8.8 %) cases (p: 0.250). The consensus diagnosis with OCT4/CD34 modified the consensus diagnosis with H&E in 8/34 (23.5 %) cases (p: 0.727), and these findings resulted in pT-restaging in 3/34 (8.8 %) cases (p: 0.500). The sources of disagreement among uropathologists were: H&E [artefactual clefts misinterpreted as LVI in 4/6 (66.7 %) cases and true foci of LVI misinterpreted as clusters of histiocytes within the vessels in 2/6 (33.3 %) cases], OCT4/CD34 [artefactual clefts misinterpreted as LVI in 2/8 (25 %) cases, true LVI misinterpreted as artefactual clefts in 2/8 (25 %) cases or floaters in 4/8 (50 %) cases]. CONCLUSIONS: OCT4/CD34 does not improve the inter-observer agreement for the assessment of LVI in OCT4(+) GCTT. Consensus diagnosis with H&E modifies the LVI status in a significant number of cases, resulting in changes of the pT stage in a relatively small subgroup. Consensus diagnosis with OCT4/CD34 provides little additional benefit since it cannot exclude mimickers of LVI such as floaters and artefactual clefts. These results argue against the adoption of this diagnostic tool for the routine assessment of OCT4(+) GCTT.
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Carcinoma Embrionario , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Eosina Amarillenta-(YS) , Hematoxilina , Seminoma/diagnóstico , Seminoma/patología , Estudios Retrospectivos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Procesos Neoplásicos , Invasividad Neoplásica , PronósticoRESUMEN
INTRODUCTION: Bilateral testicular tumors are very rare, accounting for 1%-5% of all testicular germ-cell tumors (TGCTs). The vast majority of primary bilateral TGCTs are metachronous, with synchronous tumors comprising approximately 0.5%-1% of all cases. Those occurring synchronously share mostly the same histological pattern, predominantly seminoma, with synchronous bilateral TGCTs (SBTGCTs) with discordant subtypes being extremely rare. CASE PRESENTATION: We present the case of a 20-year-old male complaining of a palpable painless right testicular mass incidentally noticed during sexual intercourse. Ultrasonography (US) and magnetic resonance imaging (MRI) of the scrotum demonstrated bilateral testicular lesions, while staging with contrast-enhanced computed tomography (CT) exhibited normal findings. Right radical orchiectomy and left testis-sparing surgery (TSS) with concomitant onco-testicular sperm extraction (onco-TESE) were initially performed. Histology of the right testis revealed a mixed germ-cell tumor, consisting of seminoma and embryonal carcinoma, while that from the left testis disclosed embryonal carcinoma and intratubular germ-cell neoplasia unclassified (IGCNU) infiltrating the surgical margins. Hence, left orchiectomy was subsequently scheduled with histology unveiling IGCNU in the greatest part of the remaining testicular parenchyma. Following adjuvant chemotherapy, with bleomycin, etoposide, and cisplatin (BEP), the patient received testosterone replacement therapy and remained free of recurrence at an 18-month follow-up. CONCLUSION: This case highlights both the rarity of a bilateral testicular tumor's synchronous appearance and its extremely infrequent discordant histopathology. A comprehensive review of the major series of SBTGCTs with discordant histology cited in the literature is additionally presented.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Adulto Joven , Adulto , Neoplasias Testiculares/patología , Carcinoma Embrionario/complicaciones , Carcinoma Embrionario/patología , Carcinoma Embrionario/cirugía , Seminoma/complicaciones , Seminoma/patología , Seminoma/cirugía , Semen , Neoplasias de Células Germinales y Embrionarias/cirugía , OrquiectomíaRESUMEN
Germ cell neoplasia in situ (GCNIS) is the precursor of both seminomatous and non-seminomatous germ cell tumors. It consists of distended tubules that may have either intratubular seminoma or intratubular embryonal carcinoma cells. Many invasive non-seminomatous tumors contain a mixture of tumor types, which are reviewed here. Morphology, aided by a panel of immunostains, can determine the presence and percent of embryonal carcinoma, yolk sac tumor, choriocarcinoma, or teratoma in such tumors. Use of immunostains, required for diagnosis in perhaps 25% of testicular neoplasms, is reviewed. Changes of classification in the AJCC (8th edition) in 2016 are discussed, including the partitioning of two tumor types: the central role of chromosome 12p amplification allows both teratoma and yolk sac tumor to be divided into prepubertal types (lacking amplification) and post-pubertal types. Occasionally, sex cord-stromal tumors, hematolymphoid tumors, or epididymal adenomatoid tumors enter the differential diagnosis of germ cell neoplasms.
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Carcinoma Embrionario , Tumor del Seno Endodérmico , Neoplasias de Células Germinales y Embrionarias , Seminoma , Teratoma , Neoplasias Testiculares , Masculino , Humanos , Tumor del Seno Endodérmico/patología , Neoplasias Testiculares/genética , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Carcinoma Embrionario/genética , Carcinoma Embrionario/metabolismo , Carcinoma Embrionario/patología , Teratoma/diagnóstico , Teratoma/genética , Teratoma/patología , Seminoma/diagnóstico , Seminoma/genética , Seminoma/patologíaRESUMEN
OBJECTIVES: Extragonadal germ cell tumors (EGCT) are a rare entity, most of them being located in the mediastinum and retroperitoneum. Information on these tumors is scarce, requiring carrying out large population-based studies to better understand these diseases. We aimed to determine the clinical features and prognosis of patients with EGCT of the mediastinum and retroperitoneum. MATERIALS AND METHODS: Demographic and clinicopathological features of patients diagnosed with EGCT of the mediastinum and retroperitoneum from 1975 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 1674 patients were included, 1297 (77.5%) of mediastinal origin and 377 (22.5%) of retroperitoneum. Nonseminomatous tumors (56.3%) were slightly more frequent than seminomas (43.7%) with similar distribution between mediastinum and retroperitoneum. After a median follow-up of 137 months, the median overall survival was 263 months (95% CI, 220-296) whereas the median cause-specific survival (CSS) has still not been reached. The 10-year overall survival and CSS were 57.4% (95% CI, 55-59.7) and 63% (95% CI, 60.6-65.2) respectively. Multivariate analysis showed that older age, mediastinal location, nonseminomatous histology, and distant disease at diagnosis were independent prognostic factors correlated with a worse prognosis. Patients with mediastinal choriocarcinoma and embryonal carcinoma have the worst prognosis, both with a median CSS of only 12 months. CONCLUSIONS: Despite a decreasing incidence observed in recent decades, EGCT continues to represent a challenge for oncologists. The prognosis of choriocarcinoma and embryonal carcinoma of the mediastinum remains poor and treatment strategies need to be improved urgently.
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Carcinoma Embrionario , Coriocarcinoma , Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Femenino , Humanos , Neoplasias del Mediastino/epidemiología , Neoplasias del Mediastino/terapia , Mediastino/patología , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/terapiaRESUMEN
BACKGROUND: Germ cell tumors (GCTs) are the most common type of cancer in Germany in young men between 15 and 44 years of age. The routinely performed diagnostic procedures are essential for the patient's treatment, but can be difficult due to heterogenous histologies. Additionally, the molecular mechanisms of the development of the special forms growing teratoma syndrome (GTS) and testicular tumors with malignant somatic transformation (MST) as well as of therapy resistance are not fully understood. OBJECTIVES: Updated understanding of the molecular processes underlying GCT development and their special forms as well as recommendations for new and useful biomarkers. RESULTS: The development of GCTs is a dynamic process largely influenced by the microenvironment. Seminomas (SEs) in particular seem to posses a higher cellular plasticity than previously assumed, allowing SEs to be reprogrammed into an embryonal carcinoma (EC) or differentiate into extra-embryonal tissues (yolk sac tumors [YSTs], trophoblastic differentiation). Novel serological (mi371a-3p) and pathological (FOXA2) biomarkers are well suited to early detect GCTs and YSTs, respectively. For more aggressive tumors and special cases (GTS, MST), there are still no reliable diagnostics or specific/tailored therapies available. CONCLUSION: The ability of SEs to transit into EC or YSTs should be considered during therapy. Future research should focus on deciphering the special forms GTS and MST as well as the early recognition of YSTs, since their development seems to be an escape mechanism to chemotherapy.
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Carcinoma Embrionario , Tumor del Seno Endodérmico , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Inmunohistoquímica , Neoplasias Testiculares/diagnóstico , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Seminoma/patología , Carcinoma Embrionario/patología , Tumor del Seno Endodérmico/patología , Biomarcadores , Microambiente TumoralRESUMEN
BACKGROUND: In recent years, several studies investigated the complex process called "reprogramming" of seminoma (S) cells. The accepted pathogenetic model is a complex network including SOX2, SOX17, OCT3/4 and PRAME, which modulates the epigenetic transcription of numerous downstream genes and drives a divergent gene expression profile resulting in the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (M-GCTT), and finally to embryonal carcinoma (EC). Herein, we tested a large cohort of GCTT with SOX2 and PRAME to evaluate their expression in the evolutionary steps of GCTT and verify if the modulation in the expression of these two molecules could be relevant for the fate of GCTT. METHODS: We tested 43, 19 and 17 consecutive and retrospectively enrolled cases of GCTT, germ cell neoplasia in situ (GCNIS) and uninvolved background testes (UBT), respectively. SOX2 and PRAME expressions have been evaluated with H-score and compared by adopting the appropriate statistic tests (Student's t-test and Mann-Whitney U test). RESULTS: We found that SOX2 was more expressed by nonseminomatous-GCTT (NS-GCTT) (p < 0.001) and EC (p < 0.001) rather than S; by contrast, PRAME showed an opposite expression profile being expressed by S but not by NS-GCTT (p < 0.001) and EC (p < 0.001). S-C showed different expressions of SOX2 and PRAME compared to both P-S (p = 0.002 and <0.001, respectively) and EC (p < 0.001 and 0.042, respectively), with intermediate values between these latter two categories. GCNIS and UBT showed no expression of SOX2 (scattered positive Leydig cells) but high H-score levels of PRAME. CONCLUSIONS: SOX2 and PRAME are differentially expressed and specularly modulated during the "reprogramming" of S cells [P-S (high levels of PRAME, no expression/low levels of SOX2) â S-C (intermediate levels of PRAME, intermediate levels of SOX2) â EC (no expression/low levels of PRAME, high levels of SOX2)], therefore supporting a complex pathogenetic model where the interactions between these two molecules are crucial in determining the fate of GCTT.
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Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/genética , Seminoma/metabolismo , Seminoma/patología , Neoplasias Testiculares/patología , Estudios Retrospectivos , Factores de Transcripción SOXB1/metabolismo , Carcinoma Embrionario/genética , Carcinoma Embrionario/metabolismo , Carcinoma Embrionario/patología , Antígenos de Neoplasias/metabolismoRESUMEN
OBJECTIVE: To systematically evaluate evidence on prognostic factors for tumor recurrence in clinical stage I nonseminoma patients other than lymphovascular invasion (LVI). METHODS: We performed a systematic literature search in the biomedical databases Medline (via Ovid) and Cochrane Central Register of Controlled Trials (search period January 2010 to February 2021) for full text publications in English and German language, reporting on retro- or prospectively assessed prognostic factors for tumor recurrence in patients with stage I nonseminomatous germ cell tumors. RESULTS: Our literature search yielded eleven studies reporting on 20 potential prognostic factors. Results are based on cohort studies of mostly moderate to low quality. Five out of eight studies found a significant association of embryonal carcinoma (EC) in the primary tumor with relapse. Among the different risk definitions of embryonal carcinoma (presence, predominance, pure), presence of EC alone seems to be sufficient for prognostification. Interesting results were found for rete testis invasion, predominant yolk sac tumor, T-stage and history of cryptorchidism, but the sparse data situation does not justify their clinical use. CONCLUSIONS: No additional factors that meet the prognostic value of LVI, especially when determined by immunohistochemistry, could be identified through our systematic search. The presence of EC might serve as a second, subordinate prognostic factor for clinical use as the data situation is less abundant than the one of LVI. Further efforts are necessary to optimize the use of these two prognostic factors and to evaluate and validate further potential factors with promising preliminary data.
Asunto(s)
Carcinoma Embrionario , Neoplasias Testiculares , Masculino , Humanos , Carcinoma Embrionario/patología , Pronóstico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Invasividad Neoplásica/patología , Neoplasias Testiculares/patologíaRESUMEN
The aims of the present study were to investigate the expression of the classic estrogen receptors ESR1 and ESR2, the splicing variant ESR1-36 and GPER in human testicular embryonal carcinoma NT2/D1 cells, and the effects of the activation of the ESR1 and ESR2 on cell proliferation. Immunostaining of ESR1, ESR2, and GPER were predominantly found in the nuclei, and less abundant in the cytoplasm. ESR1-36 isoform was predominantly expressed in the perinuclear region and cytoplasm, and some weakly immunostained in the nuclei. In nonstimulated NT2/D1 cells (control), proteins of the cell cycle CCND1, CCND2, CCNE1 and CDKN1B are present. Activation of ESR1 and ESR2 increases, respectively, CCND2 and CCNE1 expression, but not CCND1. Activation of ESR2 also mediates upregulation of the cell cycle inhibitor CDKN1B. This protein co-immunoprecipitated with CCND2. Also, E2 induces an increase in the number and viability of the NT2/D1 cells. These effects are blocked by simultaneous pretreatment with ESR1-and ESR2-selective antagonists, confirming that both estrogen receptors regulate NT2/D1 cell proliferation. In addition, E2 increases SRC phosphorylation, and SRC mediates cell proliferation. Our study provides novel insights into the signatures and molecular mechanisms of estrogen receptor in NT2/D1 cells.
Asunto(s)
Carcinoma Embrionario , Receptor alfa de Estrógeno/metabolismo , Receptores de Estrógenos , Proliferación Celular , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Humanos , Fosforilación , Receptores de Estrógenos/metabolismoRESUMEN
Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United States with a wide range of clinical presentations depending on the infected organ systems. Most infections are asymptomatic. Coccidioidomycosis causes a primary pulmonary infection and when symptoms occur, they most often resemble community-acquired pneumonia. One percent of cases disseminate, typically via hematogenous or lymphatic spread. It is in these cases that more severe symptoms may present and potentially overlap with those characteristics of other systemic illnesses. This is a case of CM disseminated to lymph nodes in a 24-year-old man with concomitant metastatic embryonal carcinoma. It is difficult to identify the primary etiology for many components of this patient's presentation, including diffuse lymphadenopathy and multiple pulmonary nodules. Furthermore, the relationship between these 2 concurrent disease processes is not entirely clear. Factors that may contribute include the well-known phenomenon of locus minoris resistentiae (LMR) or potentially a shared immune failure between infectious organisms and malignant cells.
Asunto(s)
Carcinoma Embrionario/complicaciones , Coccidioidomicosis/complicaciones , Infestaciones por Pulgas/complicaciones , Infestaciones por Piojos/complicaciones , Phthiraptera , Siphonaptera , Animales , Coccidioidomicosis/diagnóstico , Humanos , Pulmón/patología , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/parasitología , Ganglios Linfáticos/patología , Masculino , Adulto JovenRESUMEN
Induced pluripotent stem cells (iPSCs) are useful for the development of therapies in regenerative medicine, analysis of pathogenesis, and exploration of candidate drugs. We developed an alternative usage of iPSCs of which the MHC haplotype is matched to transplantable recipients in a cynomolgus macaque model. We established two cancer cell lines, embryonal carcinoma, and glioblastoma cell lines from cynomolgus monkey iPSCs. Here, we describe a method to induce the cancer cell lines including a technique for culture of the monkey iPSCs on feeder cells and the induction of hematopoietic stem cells and neural progenitor cells from monkey iPSCs.