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International Journal of Clinical and... 2017Embryonal carcinoma is a rare malignant brain tumor and stands for 5% of all intracranial germ cell tumors. Embryonal carcinoma occurs mainly in the posterior third... (Review)
Review
Embryonal carcinoma is a rare malignant brain tumor and stands for 5% of all intracranial germ cell tumors. Embryonal carcinoma occurs mainly in the posterior third ventricle and pineal region area. Preoperative imaging examination, blood serum and cerebrospinal fluid level of AFP and HCG can support the diagnosis. Subtotal to total removal with good preservation of the important structures can be achieved in this tumor resection. Embryonal carcinoma has poor prognosis result. Postoperative radiotherapy and adjuvant chemotherapy may increase the survival rate, but due to the malignant characteristics of the tumor the 5 years survival rate remains low. We presented two cases of embryonal carcinoma in children. Subtotal resection was achieved in these two patients; patient who had had postoperative radiotherapy and adjuvant chemotherapy had longer survival time than patient who had had surgery alone.
PubMed: 31966414
DOI: No ID Found -
Archives of Pathology & Laboratory... Apr 2002Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding....
Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding. We present in this report the histologic and immunohistochemical findings of 2 cases of intratubular embryonal carcinoma. One case was exclusively intratubular embryonal carcinoma without an invasive component in the same testis. A malignant mixed germ cell tumor in the contralateral testis had been previously excised. The second case is predominantly composed of intratubular embryonal carcinoma adjacent to a malignant mixed germ cell tumor. In one case, the intratubular embryonal carcinoma was immunoreactive for CD30, AE1/AE3, cytokeratin 7 focally, and p53. It was negative for cytokeratin 20, p21, and alpha-fetoprotein. These findings are strongly supportive of the opinion that intratubular embryonal carcinoma is the precursor of invasive embryonal carcinoma.
Topics: Adult; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Embryonal; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Multiple Primary; Precancerous Conditions; Testicular Neoplasms; Tumor Suppressor Protein p53
PubMed: 11900581
DOI: 10.5858/2002-126-0487-IEC -
Asian Journal of Urology Apr 2021The development of germ cell tumors (GCTs) is a unique pathogenesis occurring at an early developmental stage during specification, migration or colonization of... (Review)
Review
The development of germ cell tumors (GCTs) is a unique pathogenesis occurring at an early developmental stage during specification, migration or colonization of primordial germ cells (PGCs) in the genital ridge. Since driver mutations could not be identified so far, the involvement of the epigenetic machinery during the pathogenesis seems to play a crucial role. Currently, it is investigated whether epigenetic modifications occurring between the omnipotent two-cell stage and the pluripotent implanting PGCs might result in disturbances eventually leading to GCTs. Although progress in understanding epigenetic mechanisms during PGC development is ongoing, little is known about the complete picture of its involvement during GCT development and eventual classification into clinical subtypes. This review will shed light into the current knowledge of the complex epigenetic and molecular contribution during pathogenesis of GCTs by emphasizing on early developmental stages until arrival of late PGCs in the gonads. We questioned how misguided migrating and/or colonizing PGCs develop to either type I or type II GCTs. Additionally, we asked how pluripotency can be regulated during PGC development and which epigenetic changes contribute to GCT pathogenesis. We propose that SOX2 and SOX17 determine either embryonic stem cell-like (embryonal carcinoma) or PGC-like cell fate (seminoma). Finally, we suggest that factors secreted by the microenvironment, BMPs and BMP inhibiting molecules, dictate the fate decision of germ cell neoplasia (into seminoma and embryonal carcinoma) and seminomas (into embryonal carcinoma or extraembryonic lineage), indicating an important role of the microenvironment on GCT plasticity.
PubMed: 33996469
DOI: 10.1016/j.ajur.2020.05.009 -
Pathology, Research and Practice Feb 2023Lymphovascular 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...
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.
Topics: Male; Humans; Eosine Yellowish-(YS); Hematoxylin; Carcinoma, Embryonal; Seminoma; Retrospective Studies; Testicular Neoplasms; Neoplastic Processes; Neoplasm Invasiveness; Prognosis
PubMed: 36706585
DOI: 10.1016/j.prp.2023.154337 -
Andrology Nov 2020Testicular germ cell tumors (TGCTs) are the most common malignant cancer in young men. Although TGCTs are generally responsive to platinum-based chemotherapy...
BACKGROUND
Testicular germ cell tumors (TGCTs) are the most common malignant cancer in young men. Although TGCTs are generally responsive to platinum-based chemotherapy particularly cisplatin, acquired resistance in patients with metastasis still occurs resulting in poor prognosis. Specifically, differentiation of embryonal carcinoma (EC) cells, the stem cells of TGCTs, can lead to the reduction of cisplatin responsiveness. Therefore, novel therapeutic strategies for TGCTs are needed. System L amino acid transporters have been reported to be up-regulated and to play an important role in tumorigenesis. However, expression and role of system L amino acid transporters in TGCTs remain elusive.
MATERIALS AND METHODS
Expression of system L amino acid transporters was analyzed in TGCT samples from The Cancer Genome Atlas (TCGA). Expression of LAT1, LAT2, and 4F2hc was examined in human embryonal carcinoma cell line NTERA2. Roles of system L amino acid transporters on NTERA2 cell survival, cell proliferation, pluripotency, and cisplatin sensitivity were evaluated.
RESULTS
Based upon TCGA datasets, we found that two isoforms of system L (LAT1 and LAT2) and their chaperone protein 4F2hc are highly expressed in EC samples compared with other groups. Treatment with the system L inhibitor BCH significantly suppressed leucine uptake into the pluripotent EC cell line NTERA2. The malignant phenotypes including cell viability, cell proliferation, and clonal ability were decreased following BCH treatment. Nonetheless, system L inhibition did not alter expression of stemness genes in NTERA2 cells. After NTERA2 differentiation, expressions of LAT1 and LAT2 were decreased. Finally, co-administration of BCH enhanced cisplatin sensitivity in both undifferentiated and differentiated cells. These effects were associated with the reduction in p70S6K phosphorylation.
CONCLUSION
Taken together, these results shed light on the roles of system L amino acid transporters in TGCTs. Therefore, system L amino acid transporters could provide novel therapeutic targets for treatment against TGCTs.
Topics: Adaptor Proteins, Signal Transducing; Amino Acid Transport System L; Antineoplastic Agents; Carcinogenesis; Carcinoma, Embryonal; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Drug Resistance, Neoplasm; Embryonal Carcinoma Stem Cells; Fusion Regulatory Protein 1, Heavy Chain; Humans; Large Neutral Amino Acid-Transporter 1; Male; Testicular Neoplasms
PubMed: 32741077
DOI: 10.1111/andr.12880 -
International Journal of Molecular... Feb 2023In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/ and and... (Review)
Review
In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/ and and embryonal carcinoma (EC) has four upregulated genes, OCT4/ and 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.
Topics: Male; Humans; Epigenesis, Genetic; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Carcinoma, Embryonal; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 36835562
DOI: 10.3390/ijms24044148 -
International Journal of Molecular... Dec 2021The pluripotent transcription factor NANOG is essential for maintaining embryonic stem cells and driving tumorigenesis. We previously showed that PKC activity is...
The pluripotent transcription factor NANOG is essential for maintaining embryonic stem cells and driving tumorigenesis. We previously showed that PKC activity is involved in the regulation of NANOG expression. To explore the possible involvement of microRNAs in regulating the expression of key pluripotency factors, we performed a genome-wide analysis of microRNA expression in the embryonal carcinoma cell line NT2/D1 in the presence of the PKC activator, PMA. We found that MIR630 was significantly upregulated in PMA-treated cells. Experimentally, we showed that transfection of MIR630 mimic into embryonal carcinoma cell lines directly targeted the 3'UTR of OCT4, SOX2, and NANOG and markedly suppressed their expression. RNAhybrid and RNA22 algorithms were used to predict miRNA target sites in the 3'UTR, four possible target sites of MIR630 were identified. To examine the functional interaction between MIR630 and mRNA, the predicted MIR630 target sites in the 3'UTR were deleted and the activity of the reporters were compared. After targeted mutation of the predicted MIR630 target sites, the MIR630 mimic inhibited NANOG significantly less than the wild-type reporters. It is worth noting that mutation of a single putative binding site in the 3'UTR of did not completely abolish MIR630-mediated suppression, suggesting that MIR630 in the 3'UTR may have multiple binding sites and act together to maximally repress NANOG expression. Interestingly, MIR630 mimics significantly downregulated gene transcription. Exogenous expression of OCT4, SOX2, and lacking the 3'UTR almost completely rescued the reduced transcriptional activity of MIR630. MIR630 mediated the expression of differentiation markers in NT2/D1 cells, suggesting that MIR630 leads to the differentiation of NT2/D1 cell. Our findings show that MIR630 represses NANOG through transcriptional and post-transcriptional regulation, suggesting a direct link between core pluripotency factors and MIR630.
Topics: 3' Untranslated Regions; Binding Sites; Carcinoma, Embryonal; Cell Differentiation; Cell Line, Tumor; Embryonal Carcinoma Stem Cells; Embryonic Stem Cells; Humans; MicroRNAs; Mutation; Nanog Homeobox Protein; RNA Interference; Transcription, Genetic; Up-Regulation
PubMed: 35008480
DOI: 10.3390/ijms23010046 -
Urology Case Reports Jan 2024Extragonadal germ cell tumors originating in the prostate are extremely rare. Thus far, less than 20 cases were described in the literature. To our knowledge, there are...
Extragonadal germ cell tumors originating in the prostate are extremely rare. Thus far, less than 20 cases were described in the literature. To our knowledge, there are no published cases of primary embryonal carcinoma of the prostate. The present study presents a case of a 24-year-old male with primary prostate embryonal carcinoma. The patient received cisplatin-based chemotherapy. The patient refused a surgical treatment, which resulted in relapse of the disease and death in a short follow-up period. The present case shows that primary embryonal carcinoma may also be found in prostate and indicates the potential importance of timely surgical resection.
PubMed: 38205041
DOI: 10.1016/j.eucr.2023.102640 -
Case Reports in Gastroenterology 2021We present the case of a 35-year-old man with intractable nausea, vomiting, and severe anemia. A computed tomography (CT) scan of the chest, abdomen, and pelvis showed a...
We present the case of a 35-year-old man with intractable nausea, vomiting, and severe anemia. A computed tomography (CT) scan of the chest, abdomen, and pelvis showed a circumferential lesion thickening of up to 3.5 cm at the level of the third portion of the duodenum. No aortocaval, retroperitoneal lymphadenopathy, nor secondary lesion was observed. Esophagogastroduodenoscopy (EGD) revealed a circumferential mass within the third portion of the duodenum. Histopathology of biopsy materials from the duodenal mass showed it most likely to be a poorly differentiated adenocarcinoma. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. Histologically, tumor cells with basophilic cytoplasm and pleomorphic nuclei showed a solid pattern, and expressed CD30 and SALL4 immunohistochemically, leading to a diagnosis of embryonal carcinoma-like tumor. No other primary tumor could be identified, and the location of the tumor, mainly on the mucosal surface, suggested a duodenal origin. The UICC TNM staging was T3N2M0, stage IIB. This is a rare case of primary duodenal carcinoma with features of embryonal carcinoma.
PubMed: 33790714
DOI: 10.1159/000512421 -
Journal of Cellular and Molecular... Aug 2017So far, the understanding of germ cell cancer (GCC) pathogenesis is based on a model, where seminomas and non-seminomas represent distinct entities although originating... (Review)
Review
So far, the understanding of germ cell cancer (GCC) pathogenesis is based on a model, where seminomas and non-seminomas represent distinct entities although originating from a common precursor termed germ cell neoplasia in situ (GCNIS). Embryonal carcinomas (ECs), the stem cell population of the non-seminomas, is pluri- to totipotent and able to differentiate into cells of all three germ layers, giving rise to teratomas or tumours mimicking extraembryonic tissues (yolk sac tumours, choriocarcinomas). With regard to gene expression, (epi)genetics and histology, seminomas are highly similar to GCNIS and primordial germ cells, but limited in development. It remains elusive, whether this block in differentiation is controlled by cell intrinsic mechanisms or by signals from the surrounding microenvironment. Here, we reviewed the recent literature emphasizing the plasticity of GCCs, especially of seminomas. We propose that this plasticity is controlled by the microenvironment, allowing seminomas to transit into an EC or mixed non-seminoma and vice versa. We discuss several mechanisms and routes of reprogramming that might be responsible for this change in the cell fate. We finally integrate this plasticity into a new model of GCC pathogenesis, allowing for an alternative view on the dynamics of GCC development and progression.
Topics: Carcinoma, Embryonal; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Cellular Microenvironment; Cellular Reprogramming; Choriocarcinoma; Female; Gene Expression Regulation, Neoplastic; Hepatocyte Nuclear Factor 3-beta; Humans; Male; SOXB1 Transcription Factors; Seminoma; Signal Transduction; Teratoma
PubMed: 28244655
DOI: 10.1111/jcmm.13082