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PubMed2006

Germ cell lineage differentiation in non-seminomatous germ cell tumours.

Human germ cell tumours (GCTs) have long fascinated investigators for a number of reasons. Being pluripotential tumours, they can differentiate into both extra-embryonic and embryonic (somatic) tissues. However, it has never been shown convincingly that, in humans, these tumours are truly totipotent and can also give rise to the germ lineage, the third major differentiation lineage occurring early during embryonic life. Using a number of newly available, distinct, immunohistochemical markers, such as OCT3/4, VASA and TSPY, the occurrence of germ cells was investigated in a number of germ cell tumours. Development of germ cells was identified in three independent non-seminomas, including two pure yolk sac tumours and one mixed tumour composed of yolk sac tumour and immature teratoma. Our finding indicates a previously unknown totipotent potential of human GCTs and raises the question of whether, under certain culture conditions, primordial germ cells could be derived from human GCT cell lines.

Biomarkers↗
PubMed1994

Hepatocytic transcription factor expression in human embryonal carcinoma and yolk sac carcinoma cell lines: expression of HNF-3 alpha in models of early endodermal cell differentiation.

Retinoic acid treatment of the multipotent human embryonal carcinoma cell line GCT 27 X-1 induced differentiation into an epithelial cell type which morphologically resembled rodent visceral endoderm in vitro. The differentiated cells expressed some markers characteristic of yolk sac, such as cytokeratin 19 and extracellular matrix proteins, but none of the secreted serum proteins produced by normal yolk sac or liver. HNF-3 alpha expression increased upon retinoic acid-induced GCT 27 X-1 differentiation. This increase in HNF-3 alpha expression may characterize an early stage in the differentiation of extraembryonic endoderm. In support of this hypothesis, we found that a yolk sac carcinoma cell line with a phenotype similar to rodent visceral endoderm expressed transcripts for HNF-1 alpha, -1 beta, -3 alpha, -3 beta, -3 gamma, and 4, whereas yolk sac carcinoma cell lines resembling rodent parietal endoderm expressed transcripts for HNF-3 alpha. The results support the conclusion that hepatocytic transcription factors, particularly HNF-3 alpha, may play an important role in early endodermal differentiation in man.

Animals↗
PubMed1995

Expression of gamma-glutamyl transpeptidase in midgestation mouse yolk sac and mouse visceral yolk sac carcinoma cells.

gamma-Glutamyl transpeptidase (gamma GT) is a crucial enzyme for the metabolism of xenobiotics and endogenous mediators of biological functions (leukotrienes, prostaglandins, and hepoxillins). Yet little is known about its potential role during development. It is a single copy gene expressed from at least seven promoters. Using histochemistry and immunohistochemistry we demonstrate that gamma GT first appears in the midgestational yolk sacs of mouse embryos. Established cell lines with phenotypic features of yolk sac endoderm (JC-44) or embryonic stem cells were also assayed for the expression of gamma GT. Significant levels were detected in JC-44 cells and higher levels were found in JC-44-derived embryoid bodies. Because this cell line appears to be a good in vitro counterpart of yolk sac differentiation, we characterized the gamma GT mRNA types expressed in JC-44 cells. By ribonuclease protection analysis, gamma GT RNA types IV and VI represent about 80% of the total gamma GT RNA in JC-44 embryoid bodies. Reverse transcription-mediated polymerase chain reaction detected low amounts of gamma GT RNA types I, III, and V. Expression of gamma GT in yolk sac follows a pattern seen in many tissues in which one or two gamma GT RNA types dominate the expression profile; however, the reason for this tissue specificity is unknown.

Animals↗
PubMed1996

Interphase cytogenetics on paraffin sections of paediatric extragonadal yolk sac tumours.

Germ cell tumours in children are more often extragonadal than in adults and the most frequent type is the yolk sac tumour. Limited cytogenetic data exist on extragonadal yolk sac tumours in children. We applied in situ hybridization (ISH) to interphase cell nuclei of four paediatric extragonadal pure yolk sac tumours and one yolk sac tumour component of a mixed germ cell tumour using paraffin-embedded tissue sections. The panel of chromosome-specific DNA probes was selected on the basis of their relevance in adult germ cell tumours and consisted of five DNA probes specific for the (peri)centromeric regions of chromosomes 1, 8, 12, and/or 17, X and/or one DNA probe specific for the subtelomeric region of chromosome 1 (p36.3). Only one tumour failed to show numerical and structural chromosome aberrations with the DNA probes used. The other four had an increased incidence of numerical chromosome aberrations with an over-representation of at least one chromosome. The DNA indices determined in the paraffin-embedded tumour material correlated well with the in situ hybridization findings. In only a few cases were chromosomes over-represented, when compared with the corresponding DNA indices. Recently, we have shown that the short arm of chromosome 1 is a non-random site of deletion in paediatric gonadal pure yolk sac tumours. The occurrence of similar deletions in one extragonadal pure yolk sac tumour and in one yolk sac tumour component, in conjunction with two further ISH reports, suggests that the loss of gene(s) in this region is an important event in the pathogenesis of paediatric malignant germ cell tumours of nearly all sites.

Adolescent↗
PubMed1999

Fertility-sparing treatment of patients with ovarian cancer.

Ovarian malignancies in reproductive age women often provide the physician and patient with a management dilemma. Many investigators have proposed conservative management in early-stage disease. This article provides evidence supporting fertility-sparing management in young women with early ovarian malignancies.

Adenocarcinoma↗
PubMed2004

Frontal intraparenchymal schwannoma: an unusual presentation.

CASE REPORT: A 13-year-old male with an 11-year history of a seizure disorder presented with recent onset raised intracranial pressure symptoms and no obvious phakomatosis. CT revealed a heterogeneous, frontal, intra-axial, densely enhancing, solid lesion with intense perilesional oedema and mass effect. Total microsurgical excision resulted in cure. Histopathological examination showed characteristic Antoni A and B areas and occasional Verocay bodies consistent with the diagnosis of an intraparenchymal schwannoma. DISCUSSION: The authors present a very rare, entirely solid manifestation of this highly uncommon lesion seen mostly in young adults and children with symptoms suggestive of raised intracranial pressure and associated seizure disorders. The possible developmental origins are discussed.

Adolescent↗
PubMed1992

Management of neutropenic colitis.

Neutropenic colitis is recognized as a rare complication of chemotherapy in haematological malignancies. By contrast, the complication is less well known in relationship to chemotherapy for solid malignancies. There are very few examples reported and this paper adds three further cases and reviews the literature. We emphasize that although some cases of neutropenic colitis may be managed medically, full thickness involvement of the bowel wall may lead to perforation and require surgery. The pathogenesis of this progression is discussed and it is concluded that clinical awareness is important in the diagnosis. The signs of peritonitis or septicaemia are indications for excisional surgery with the formation of a temporary ileostomy.

Adrenal Gland Neoplasms↗
PubMed2006

Yolk sac tumours of the ovary: an update.

AIMS: Yolk sac tumours of the ovary (YST), also called endodermal sinus tumours (EST) are rare and highly malignant tumours of utmost importance occurring in children and young adults. In the past, outcome was very poor and the disease was almost always fatal. With the refinement of chemotherapeutic regimens in the last several decades, survival rates have improved dramatically and fertility preserving surgery has become possible. The aim of this review is to provide the reader with an analysis of the available literature and a rational approach to patient management. METHODS: We performed a literature search in the PubMed database and the reference lists of relevant articles concerning yolk sac tumours of the ovary. FINDINGS AND CONCLUSION: There are no randomised studies relating to the management of YST of the ovary. The available literature is composed of retrospective reviews and case reports that span several decades. Prognosis nowadays is good in stage I and II but still comparable to that of ovarian epithelial cancer in stage III and IV. The overall good prognosis is due to the fact that most of ovarian YST are diagnosed at an early stage where 5years survival reaches 95%. Appropriate surgical treatment for patients where fertility needs to be preserved consists in laparotomy with unilateral salpingo-oophorectomy, peritoneal cytologic studies, omentectomy, multiple peritoneal and abdominal biopsies and resection of all visible disease. Three courses of BEP (bleomycin, etoposide, cisplatin) is the current standard therapy and four courses is recommended in case of bulky residual disease after surgery. Serum alpha-feto-protein (AFP) is a useful marker for the diagnosis and management of YST.

Endodermal Sinus Tumor↗
PubMed1999

Detection of circulating testicular cancer cells in peripheral blood.

Patients who receive peripheral blood stem cell transplants are at risk of developing cancer recurrence due to the presence of malignant cells in the transplants. We investigated a sensitive method to detect malignant cells in the peripheral blood and peripheral blood stem cells of patients with testicular cancer using nested, reverse transcription-polymerase chain reaction (RT-PCR) to measure alpha-fetoprotein gene expression. Using this technique, a single cancer cell could be detected in 10(6) peripheral blood mononuclear cells. This is the first report of an attempt to detect circulating malignant cells in the peripheral blood of patients with testicular cancer by nested RT-PCR.

Actins↗