Embryonal Carcinoma (embryonal + carcinoma)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Embryonal Carcinoma

  • embryonal carcinoma cell

  • Selected Abstracts


    Roles of the conserved CCAAT and GC boxes of the human and mouse type II transforming growth factor-, receptor genes

    MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2003
    Cory T. Bernadt
    Abstract Embryonal carcinoma (EC) cells are used widely to study the molecular mechanisms that regulate the transcription of genes during mammalian embryogenesis. The type II transforming growth factor-, receptor (T,R-II) gene is expressed at very low levels by mouse EC cells prior to differentiation. Differentiation of EC cells results in increases of both the steady-state levels of T,R-II mRNA and the activity of the T,R-II promoter. Several cis -regulatory elements have been shown previously to regulate the T,R-II gene. This study focuses on the role of a CCAAT box and three GC boxes in the regulation of the human and mouse T,R-II promoters in EC-differentiated cells. We demonstrate that the CCAAT box and two flanking GC boxes, Sp A and Sp B, function as positive regulatory elements in the human T,R-II promoter, and that the transcription factor complex NF-Y positively regulates the human T,R-II promoter through the CCAAT box motif. We also show that the CCAAT box and the downstream GC box Sp B, which are conserved between the human and mouse promoters, behave as positive regulatory elements in the mouse T,R-II promoter. In addition, we demonstrate that the transcription factor Sp1 can bind to the Sp B GC box in vitro. Finally, we show that a GC box located 25 bp upstream of the major transcription start site of the T,R-II gene plays a minimal role in the function of the T,R-II promoter in EC-differentiated cells. Together, our studies highlight important differences and similarities in the cis -regulatory elements that regulate the human and mouse T,R-II promoters. Mol. Reprod. Dev. 65: 353,365, 2003. © 2003 Wiley-Liss, Inc. [source]


    Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance,

    THE JOURNAL OF PATHOLOGY, Issue 4 2010
    Hendrik Wermann
    Abstract Differences in the global methylation pattern, ie hyper- as well as hypo-methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5- cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam-2 before and after demethylation using 5-azacytidine. Exposure to 5-azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell-specific marker VASA, showed increased expression. Following treatment with 5-azacytidine, TCam-2 cells were analysed using a high-throughput methylation screen for changes in the methylation sites of 14 000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]


    Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adults

    GENES, CHROMOSOMES AND CANCER, Issue 7 2008
    Alan McIntyre
    Testicular germ cell tumors (TGCTs) of adults and adolescents are thought to be derived from primordial germ cells or gonocytes. TGCTs develop postpuberty from precursor lesions known as intratubular germ cell neoplasia undifferentiated. The tumors can be divided into two groups based on their histology and clinical behavior; seminomas resemble primordial germ cells or gonocytes and nonseminomas resemble embryonic or extraembryonic tissues at various stages of differentiation. The most undifferentiated form of nonseminoma, embryonal carcinoma, resembles embryonic stem cells in terms of morphology and expression profiling, both mRNAs and microRNAs. Evidence supports both environmental factors and genetic predisposition underlying the development of TGCTs. Various models of development have been proposed and are discussed. In TGCTs, gain of material from the short arm of chromosome 12 is invariable: genes from this region include the proto-oncogene KRAS, which has activating mutations in ,10% of tumors or is frequently overexpressed. A number of different approaches to increase the understanding of the development and progression of TGCTs have highlighted the involvement of KIT, RAS/RAF/MAPK, STAT, and PI3K/AKT signaling. We review the role of these signaling pathways in this process and the potential influence of environmental factors in the development of TGCTs. © 2008 Wiley-Liss, Inc. [source]


    Further characterization of the first seminoma cell line TCam-2

    GENES, CHROMOSOMES AND CANCER, Issue 3 2008
    Jeroen de Jong
    Testicular germ cell tumors of adolescents and adults (TGCTs) can be classified into seminomatous and nonseminomatous tumors. Various nonseminomatous cell lines, predominantly embryonal carcinoma, have been established and proven to be valuable for pathobiological and clinical studies. So far, no cell lines have been derived from seminoma which constitutes more than 50% of invasive TGCTs. Such a cell line is essential for experimental investigation of biological characteristics of the cell of origin of TGCTs, i.e., carcinoma in situ of the testis, which shows characteristics of a seminoma cell. Before a cell line can be used as model, it must be verified regarding its origin and characteristics. Therefore, a multidisciplinary approach was undertaken on TCam-2 cells, supposedly the first seminoma cell line. Fluorescence in situ hybridization, array comparative genomic hybridization, and spectral karyotyping demonstrated an aneuploid DNA content, with gain of 12p, characteristic for TGCTs. Genome wide mRNA and microRNA expression profiling supported the seminoma origin, in line with the biallelic expression of imprinted genes IGF2/H19 and associated demethylation of the imprinting control region. Moreover, the presence of specific markers, demonstrated by immunohistochemistry, including (wild type) KIT, stem cell factor, placental alkaline phosphatase, OCT3/4 (also demonstrated by a specific Q-PCR) and NANOG, and the absence of CD30, SSX2-4, and SOX2, confirms that TCam-2 is a seminoma cell line. Although mutations in oncogenes and tumor suppressor genes are rather rare in TGCTs, TCam-2 had a mutated BRAF gene (V600E), which likely explains the fact that these cells could be propagated in vitro. In conclusion, TCam-2 is the first well-characterized seminoma-derived cell line, with an exceptional mutation, rarely found in TGCTs. © 2007 Wiley-Liss, Inc. [source]


    Lipoprotein lipase and endothelial lipase in human testis and in germ cell neoplasms

    INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2010
    J. E. Nielsen
    Summary The aim of this study was to investigate endothelial lipase (EL, LIPG) and lipoprotein lipase (LPL) mRNA and protein expression in normal human testis and testicular germ cell tumours (GCT). Both EL and LPL were expressed in normal seminiferous tubules and in the interstitial compartment. EL mRNA and protein were found in all germ cells as well as in Sertoli and Leydig cells. EL mRNA was abundant in pre-invasive carcinoma in situ (CIS) cells and GCTs, and EL protein was present in the cytoplasm of these cells. LPL mRNA was also relatively abundant in germ cells, Sertoli cells, CIS cells and GCTs. The LPL protein, however, was restricted to the cell membranes of pachytene spermatocytes and spermatids in normal tubules, absent from CIS cells and scarcely represented in tumours. The distribution of LPL protein in non-seminomas resembled the distribution of OCT3/4, a marker of embryonal carcinoma. The results suggest that both EL and LPL participate in the supply of nutrients and steroidogenesis in the testes, and that especially EL may be important for the supply of cholesterol for testosterone production in the Leydig cells. The partial cellular separation of the expression of the two lipases in normal testis suggests the existence of distinct biological roles, perhaps developmentally regulated, as indicated by the LPL expression in GCTs with embryonic features. A high expression of EL and abundance of lipid in tubules with CIS may have a diagnostic value. [source]


    Symposium 10: Differentiation Plasticity of Stem Cells

    JOURNAL OF NEUROCHEMISTRY, Issue 2002
    S. S. Liour
    The major role of radial glial cells in neuronal development is to provide support and guidance for neuronal migration. In vitro, neurons, astrocytes and oligodendrocytes have also been generated from neural stem cells and embryonic stem cells, but the generation of radial glial cells in vitro has not yet been reported. Since radial glial cells can lead to neurons and astrocytes during brain development, neurogenesis and gliogenesis of stem cells in vitro may at least in part also utilize the same mechanisms. To test this hypothesis, we utilized five different clones of embryonic (ES) and embryonal carcinoma (EC) stem cell lines to investigate the differentiation of radial glial cells during in vitro neural differentiation. Here, we demonstrate that radial glial cells can be generated from ES/EC cell lines. These ES/EC cell-derived radial glial cells are similar in morphology to radial glial cells in vivo. They also express several cytoskeletal markers that are characteristics of radial glial cells in vivo. The processes of these in vitro -generated radial glial cells are organized into scaffolds that appear to support the migration of newly generated neurons in culture. Like radial glial cells in vivo, they appear to differentiate subsequently into astrocytes. Differentiation of radial glial cells may be a common pathway during in vitro neural differentiation of ES cells. This novel in vitro model system may facilitate the investigation of regulation of radial glial cell differentiation and its biological function. Acknowledgements:, Supported by USPHS Grant NS11853 and a grant from the Children's Medical Research Foundation. [source]


    Glial-guided neuronal migration in P19 embryonal carcinoma stem cell aggregates

    JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005
    Marcelo F. Santiago
    Abstract During development of the nervous system, neuronal precursors that originated in proliferative regions migrate along radial glial fibers to reach their final destination. P19 embryonal carcinoma (EC) stem cells exposed to retinoic acid (RA) differentiate into neurons, glia, and fibroblast-like cells. In this work, we induced P19 aggregates for 4 days with RA and plated them onto tissue culture dishes coated with poly-L-lysine. Several cells migrated out of and/or extended processes from the aggregates after 24 hr. Some cell processes were morphologically similar to radial glial fibers and stained for glial fibrillar acidic protein (GFAP) and nestin. Large numbers of migrating cells showed characteristics similar to those of bipolar migrating neurons and expressed the neuronal marker microtubule-associated protein 2. Furthermore, scanning electron microscopy analysis revealed an intimate association between the radial fibers and the migrating cells. Therefore, the migration of neuron-like cells on radial glia fibers in differentiated P19 aggregates resembled some of the migration models used thus far to study gliophilic neuronal migration. In addition, HPTLC analysis in this system showed the expression of 9-O-acetyl GD3, a ganglioside that has been associated with neuronal migration. Antibody perturbation assays showed that immunoblockage of 9-O-acetyl GD3 arrested neuronal migration in a reversible manner. In summary, we have characterized a new cell culture model for investigation of glial-guided neuronal migration and have shown that 9-O-acetyl GD3 ganglioside has an important role in this phenomenon. © 2005 Wiley-Liss, Inc. [source]


    Regulation of the Nanog gene by both positive and negative cis -regulatory elements in embryonal carcinoma cells and embryonic stem cells

    MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2009
    Brian Boer
    Abstract The transcription factor Nanog is essential for mammalian embryogenesis, as well as the pluripotency of embryonic stem (ES) cells. Work with ES cells and embryonal carcinoma (EC) cells previously identified positive and negative cis -regulatory elements that influence the activity of the Nanog promoter, including adjacent cis -regulatory elements that bind Sox2 and Oct-3/4. Given the importance of Nanog during mammalian development, we examined the cis -regulatory elements required for Nanog promoter activity more closely. In this study, we demonstrate that two positive cis -regulatory elements previously shown to be active in F9 EC cells are also active in ES cells. We also identify a novel negative regulatory region that is located in close proximity to two other positive Nanog cis -regulatory elements. Although this negative regulatory region is active in F9 EC cells and ES cells, it is inactive in P19 EC cells. Furthermore, we demonstrate that one of the positive cis -regulatory elements active in F9 EC cells and ES cells is inactive in P19 EC cells. Together, these and other studies suggest that Nanog transcription is regulated by the interplay of positive and negative cis -regulatory elements. Given that P19 appears to be more closely related to a later developmental stage of mammalian development than F9 and ES cells, differential utilization of cis -regulatory elements may reflect mechanisms used during development to achieve the correct level of Nanog expression as embryogenesis unfolds. Mol. Reprod. Dev. 76: 173,182, 2009. © 2008 Wiley-Liss, Inc. [source]


    Distal enhancer of the mouse FGF-4 gene and its human counterpart exhibit differential activity: Critical role of a GT box

    MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2005
    Brian Boer
    Abstract Previous studies have shown that there is a strict requirement for fibroblast growth factor-4 (FGF-4) during mammalian embryogenesis, and that FGF-4 expression in embryonic stem (ES) cells and embryonal carcinoma (EC) cells are controlled by a powerful downstream distal enhancer. More recently, mouse ES cells were shown to express significantly more FGF-4 mRNA than human ES cells. In the work reported here, we demonstrate that mouse EC cells also express far more FGF-4 mRNA than human EC cells. Using a panel of FGF-4 promoter/reporter gene constructs, we demonstrate that the enhancer of the mouse FGF-4 gene is approximately tenfold more active than its human counterpart. Moreover, we demonstrate that the critical difference between the mouse and the human FGF-4 enhancer is a 4 bp difference in the sequence of an essential GT box. Importantly, we demonstrate that changing 4 bp in the human enhancer to match the sequence of the mouse GT box elevates the activity of the human FGF-4 enhancer to the same level as that of the mouse enhancer. We extended these studies by examining the roles of Sp1 and Sp3 in FGF-4 expression. Although we demonstrate that Sp3, but not Sp1, can activate the FGF-4 promoter when artificially tethered to the FGF-4 enhancer, we show that Sp3 is not essential for expression of FGF-4 mRNA in mouse ES cells. Finally, our studies with human EC cells suggest that the factor responsible for mediating the effect of the mouse GT box is unlikely to be Sp1 or Sp3, and this factor is either not expressed in human EC cells or it is not sufficiently active in these cells. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc. [source]


    Hepatoid variant of yolk sac tumor of the testis

    PATHOLOGY INTERNATIONAL, Issue 9 2000
    Yasushi Horie
    A case of testicular yolk sac tumor (endodermal sinus tumor) consisting predominantly of hepatoid cells is documented. A mass measuring approximately 4 × 3 cm was noted in the left testis of a 64-year-old man. Preoperative examination revealed an elevated serum level of , -fetoprotein (5479 ng/mL). Histologically, the lesion was composed predominantly of sheet-like or trabecular proliferation of hepatocyte-like cells with eosinophilic or clear cytoplasm. The tumor cells were immunoreactive for , -fetoprotein, antimitochondrial antibody, cytokeratin (AE1/AE3), , -1-antichymotrypsin, , -1-antitrypsin, albumin, carcinoembryonic antigen and epithelial membrane antigen. It was necessary to distinguish this variant lesion from metastatic hepatocellular carcinoma, embryonal carcinoma and hepatoid carcinoma. [source]


    OCT4: biological functions and clinical applications as a marker of germ cell neoplasia

    THE JOURNAL OF PATHOLOGY, Issue 1 2007
    L Cheng
    Abstract Germ cell tumours (GCTs) are a heterogeneous group of neoplasms, which develop in the gonads as well as in extragonadal sites, that share morphological patterns and an overall good prognosis, owing to their responsiveness to current surgical, chemotherapeutic, and radiotherapeutic measures. GCTs demonstrate extremely interesting biological features because of their close relationships with normal embryonal development as demonstrated by the pluripotentiality of some undifferentiated GCT variants. The similarities between GCTs and normal germ cell development have made it possible to identify possible pathogenetic pathways in neoplastic transformation and progression of GCTs. Genotypic and immunophenotypic profiles of these tumours are also useful in establishing and narrowing the differential diagnosis in cases of suspected GCTs. Recently, OCT4 (also known as OCT3 or POU5F1), a transcription factor that has been recognized as fundamental in the maintenance of pluripotency in embryonic stem cells and primordial germ cells, has been proposed as a useful marker for GCTs that exhibit features of pluripotentiality, specifically seminoma/dysgerminoma/germinoma and embryonal carcinoma. The development of commercially available OCT4-specific antibodies suitable for immunohistochemistry on paraffin-embedded specimens has generated increasing numbers of reports of OCT4 expression in a wide variety of gonadal and extragonadal GCTs. OCT4 immunostaining has been shown to be a sensitive and specific marker for seminomatous/(dys)germinomatous tumours and in embryonal carcinoma variants of non-seminomatous GCTs, whether in primary gonadal or extragonadal sites or in metastatic lesions. Therefore, OCT4 immunohistochemistry is an additional helpful marker both in the differential diagnosis of specific histological subtypes of GCTs and in establishing a germ cell origin for some metastatic tumours of uncertain primary. OCT4 expression has also been reported in pre-invasive conditions such as intratubular germ cell neoplasia, unclassified (IGCNU) and the germ cell component of gonadoblastoma. Additionally, OCT4 immunostaining shows promise as a useful tool in managing patients known to be at high risk for the development of invasive GCTs. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]


    Hand-assisted laparoscopic lymphadenectomy: a novel approach to a difficult area

    ANZ JOURNAL OF SURGERY, Issue 9 2003
    Andrew Sutherland
    Background: Hand-assisted laparoscopic surgery (HALS) is an emerging technique that is gaining acceptance for a wide range of abdominal procedures. We drew upon our growing experience with hand-assisted laparoscopic and thoracoscopic surgery to manage a case that was felt to require a major thoracoabdominal incision if it were to be completed by conventional open surgery. Methods: A technique is described that combines the advantages of both laparoscopic and open surgery in the form of hand-assisted laparoscopic surgery to permit safe dissection of a retrocrural mass extending into the chest. Results: We used this technique successfully to completely resect a nodal deposit of metastatic embryonal carcinoma previously thought to be inaccessible to surgical resection. Conclusion: The use of hand-assisted laparoscopic surgery improves tactile and visual feedback for the operator. This allows complex procedures involving delicate dissection to be completed safely and with less morbidity than open surgery. [source]


    Twist is inversely associated with claudins in germ cell tumors of the testis

    APMIS, Issue 9 2010
    PÄIVI VÄRE
    Väre P, Soini Y. Twist is inversely associated with claudins in germ cell tumors of the testis. APMIS 2010; 118: 640,7. We investigated the expression of claudins 1, 3,7 and transcriptional factor twist in a set of testicular germ cell tumors. The material consisted of 17 seminomas, 13 teratomas, 9 teratocarcinomas, 20 embryonal carcinomas and 9 mixed germ cell tumors. They were immunostained with antibodies to claudins 1, 3,7 and twist. As expected, all claudins were variably present in germ cell tumors with epithelial elements or differentiation, but the intensity of expression varied depending on the claudin type. Mesenchymal elements in teratomatous tumors remained negative for claudins. Expression of different claudins was less intense and inconsistent in other types of germ cell tumors. Choriocarcinomatous elements in germ cell tumors expressed relatively strongly claudin 4 and weaker positivity for claudins 5,7, while claudins 1 and 3 were negative. Seminomas showed expression only for claudins 5 and 7. The transcriptional factor twist was most strongly expressed in seminoma followed by embryonal carcinoma. Twist expression was inversely associated with several claudins (claudins 1, 3, 4 and 6). Germ cell tumors vary in their expression of claudins 1,7. Twist expression was inversely associated with several claudins, suggesting that it takes part in the downregulation of claudins in testicular tumors. [source]


    Aurora B expression in post-puberal testicular germ cell tumours,

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2009
    Francesco Esposito
    Aurora/Ipl1-related kinases are a conserved family of proteins that are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumours and have been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy, and genomic instability. Previous studies of our group have shown that Aurora B expression is restricted to specific germinal cells. In this study, we have evaluated by immunohistochemical analysis Aurora B expression in post-puberal testicular germ cell tumours (22 seminomas, 2 teratomas, 15 embryonal carcinomas, 5 mixed germinal tumours with a prominent yolk sac tumour component and 1 choriocarcinoma). The Aurora B protein expression was detected in all intratubular germ cell tumours, seminomas and embryonal carcinomas analysed but not in teratomas and yolk sac carcinomas. The immunohistochemical data were further confirmed by Western blot analysis. In addition, the kinase Aurora B was vigorously expressed in GC-1 cells line derived from murine spermatogonia. The block of Aurora B function induced by a pharmacological inhibitor significantly reduced the growth of GC-1 cells suggesting that Aurora B is a potential therapeutic target. J. Cell. Physiol. 221: 435,439, 2009. © 2009 Wiley-Liss, Inc. [source]


    Twist is inversely associated with claudins in germ cell tumors of the testis

    APMIS, Issue 9 2010
    PÄIVI VÄRE
    Väre P, Soini Y. Twist is inversely associated with claudins in germ cell tumors of the testis. APMIS 2010; 118: 640,7. We investigated the expression of claudins 1, 3,7 and transcriptional factor twist in a set of testicular germ cell tumors. The material consisted of 17 seminomas, 13 teratomas, 9 teratocarcinomas, 20 embryonal carcinomas and 9 mixed germ cell tumors. They were immunostained with antibodies to claudins 1, 3,7 and twist. As expected, all claudins were variably present in germ cell tumors with epithelial elements or differentiation, but the intensity of expression varied depending on the claudin type. Mesenchymal elements in teratomatous tumors remained negative for claudins. Expression of different claudins was less intense and inconsistent in other types of germ cell tumors. Choriocarcinomatous elements in germ cell tumors expressed relatively strongly claudin 4 and weaker positivity for claudins 5,7, while claudins 1 and 3 were negative. Seminomas showed expression only for claudins 5 and 7. The transcriptional factor twist was most strongly expressed in seminoma followed by embryonal carcinoma. Twist expression was inversely associated with several claudins (claudins 1, 3, 4 and 6). Germ cell tumors vary in their expression of claudins 1,7. Twist expression was inversely associated with several claudins, suggesting that it takes part in the downregulation of claudins in testicular tumors. [source]


    SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

    CANCER, Issue 12 2009
    Dengfeng Cao MD
    Abstract BACKGROUND: The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self-renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors. METHODS: Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity. RESULTS: All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells). CONCLUSIONS: SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors. Cancer 2009. © 2009 American Cancer Society. [source]