Grete Krag Jacobsen
Copenhagen University Hospital
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Featured researches published by Grete Krag Jacobsen.
European Urology | 1993
E. Rajpert-De Meyts; Niels Erik Skakkebæk; R. T. D. Oliver; Grete Krag Jacobsen; K. Kula; J. Slowikowska-Hilczer; C. C. Wylie; Sophie D. Fosså
The peak incidence of testicular cancer in young men suggests that gestational development and events during early infancy and puberty are important in the pathogenesis of the disease. There are two potentially significant events: the transformation of fetal germ cells into carcinoma-in-situ cells (CIS) and later conversion of CIS cells into fully invasive cancer. Several hypotheses suggest an endocrinological background to testicular neoplasia. Based on epidemiological and experimental evidence, the possible role of oestrogens, androgens and gonadotrophins is discussed in this review. The role of Sertoli cells and the importance of interplay between endocrine and paracrine factors is also stressed
Histopathology | 2003
E. Rajpert-De Meyts; Grete Krag Jacobsen; Jirina Bartkova; Florence Aubry; Michel Samson; Jiri Bartek; Niels Erik Skakkebæk
Aims: Spermatocytic seminoma is a rare germ cell derived tumour of the testis that occurs mainly in older men. We analysed the expression of recently discovered markers for germ cell differentiation and the mitosis–meiosis transition in order to define the antigen profile for diagnostic purposes and to clarify the biology and histogenesis of spermatocytic seminoma.
Human Reproduction | 2008
David Møbjerg Kristensen; John Nielsen; Niels E. Skakkebæk; Niels Graem; Grete Krag Jacobsen; Ewa Rajpert-De Meyts; Henrik Leffers
BACKGROUND UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 and REX-1 during human gonadal development and in TGCT. METHODS Expression of UTF-1 and REX-1 was studied in 52 specimens from human gonadal development and in 86 samples from TGCT. RESULTS UTF-1 and REX-1 were expressed throughout male gonadal development. In the mature testis, UTF-1 was expressed in spermatogonia, whereas REX-1 was expressed in meiotic cells and, together with OCT-3/4, in primary oocytes. Both UTF-1 and REX-1 were expressed in testicular carcinoma in situ and in TGCT. Contrarily to REX-1, UTF-1 was expressed in all spermatocytic seminomas. CONCLUSIONS Unlike other pluripotency markers NANOG and OCT-3/4, UTF-1 and REX-1 are expressed throughout human testes development. The expression pattern indicated that UTF-1 plays a possible role in spermatogonial self-renewal, whereas expression of REX-1 in meiotic cells from both testes and ovary indicate a role in meiosis. UFT-1 and REX-1 are expressed in TGCT and the high abundance of UTF-1 in spermatocytic seminomas is consistent with the hypothesis that this tumour type originates from spermatogonia.
Laboratory Investigation | 2002
Anne-Pascale Satie; Ewa Rajpert-De Meyts; Giulio C Spagnoli; Sébastien Henno; Laurence Olivo; Grete Krag Jacobsen; Nathalie Rioux-Leclercq; Bernard Jégou; Michel Samson
Cancer/testis genes are potential targets for therapeutic genetic and immunologic approaches, and are highly expressed in a large variety of human cancers. However, they are not expressed in normal tissues, with the exception of the testis. The NY-ESO-1 gene is the most recently identified member of the cancer/testis family and its product is one of the most immunogenic tumor antigens. We used immunohistochemistry to investigate the expression of NY-ESO-1 in healthy human prenatal and adult testes and in 59 human testicular tumors of different subtypes. We found that NY-ESO-1 was expressed from 18 weeks until birth in human fetal testes. In the adult testis, NY-ESO-1 was strongly expressed in spermatogonia and in primary spermatocytes, but not in post-meiotic cells or in testicular somatic cells. NY-ESO-1 was not expressed in the Sertoli cells, Leydig cells, classical seminomas, or nonseminomatous germ cells in the 59 testicular tumors. In contrast, NY-ESO-1 was expressed both in carcinomas in situ, which are the earliest stage of testicular tumors (7 of 15 cases), and in spermatocytic seminomas, which are believed to be derived from spermatogonia or primary spermatocytes (8 of 16 cases). We conclude that NY-ESO-1 is a marker that can be used to follow the early progression of testicular tumorigenesis when the tumors present a similar pattern of expression to the cells from which they originated, although the later tumors cease to express NY-ESO-1.
The Journal of Pathology | 2011
Jasmine Lim; Anne Goriely; Gareth D. H. Turner; K.A. Ewen; Grete Krag Jacobsen; Niels Graem; Andrew O.M. Wilkie; Ewa Rajpert-De Meyts
Spermatocytic seminoma (SS) is a rare testicular neoplasm that occurs predominantly in older men. In this study, we aimed to shed light on the histogenesis of SS by investigating the developmental expression of protein markers that identify distinct subpopulations of human spermatogonia in the normal adult testis. We analysed the expression pattern of OCT2, SSX2‐4, and SAGE1 in 36 SS cases and four intratubular SS (ISS) as well as a series of normal testis samples throughout development. We describe for the first time two different types of SS characterized by OCT2 or SSX2‐4 immunoexpression. These findings are consistent with the mutually exclusive antigenic profile of these markers during different stages of testicular development and in the normal adult testis. OCT2 was expressed predominantly in Adark spermatogonia, SSX2‐4 was present in Apale and B spermatogonia and leptotene spermatocytes, whilst SAGE1 was exclusively present in a subset of post‐pubertal germ cells, most likely B spermatogonia. The presence of OCT2 and SSX2‐4 in distinct subsets of germ cells implies that these markers represent germ cells at different maturation stages. Analysis of SAGE1 and SSX2‐4 in ISS showed spatial differences suggesting ongoing maturation of germ cells during progression of SS tumourigenesis. We conclude that the expression pattern of OCT2, SSX2‐4, and SAGE1 supports the origin of SS from spermatogonia and provides new evidence for heterogeneity of this tumour, potentially linked either to the cellular origin of SS or to partial differentiation during tumour progression, including a hitherto unknown OCT2‐positive variant of the tumour likely derived from Adark spermatogonia. Copyright
Acta Oncologica | 2002
Finn Edler von Eyben; Ebbe Lindegaard Madsen; Ole Blaabjerg; Per Hyltoft Petersen; Grete Krag Jacobsen; Lena Specht; Bent Pedersen; Hans von der Maase
Serum lactate dehydrogenase isoenzyme 1 catalytic concentration (S-LD-1) was measured in patients with testicular seminoma clinical stage I followed with surveillance after orchiectomy. The serum samples were obtained before orchiectomy in 110 patients (group A) and soon after orchiectomy in 55 patients (group B). In group A, 60 patients (55%) had elevated S-LD-1 and 10 patients (9%) had elevated serum human chorionic gonadotropin concentrations (S-hCG). In group B, median S-LD-1 was lower than that of group A and decreased with increasing time after orchiectomy (p=0.001, Jonckheere-Terpstra test, one-sided). After a median follow-up of 5.1 years, 23 patients (21%) in group A had relapses. The patients with elevated S-LD-1 and those with normal S-LD-1 had a similar relapse-free survival (p=0.79, log-rank test). Thus patients with seminoma stage I had elevated S-LD-1 more often than elevated S-hCG but an elevation in S-LD-1 did not predict a relapse during follow-up with surveillance. Further studies are required to elucidate the value of S-LD-1 in monitoring the surveillance of patients with seminoma stage I.
Andrologia | 2012
John Nielsen; David Møbjerg Kristensen; Kristian Almstrup; Anne Jørgensen; Inge A. Olesen; Grete Krag Jacobsen; T. Horn; Niels Erik Skakkebæk; Henrik Leffers; E. Rajpert-De Meyts
Prompted by the recently reported expression of POU5F1 (OCT3/4) in epididymis, a panel of markers for carcinoma in situ (CIS) testis and testicular germ cell tumours (TGCT), including AP‐2γ(TFAP2C), NANOG, OCT3/4, KIT, placental‐like alkaline phosphatase (PLAP), M2A/PDPN and MAGE‐A4 were examined by immunohistochemistry or in situ hybridisation in urogenital epithelia, which may interfere with detection of CIS cells in semen. In addition to OCT3/4, the expression of AP‐2γ and NANOG or their variants was detected in urogenital epithelia, while other CIS markers, including PLAP/alkaline phosphatase were absent. A combination of immunocytological staining for AP‐2γ or OCT3/4 and rapid cytochemical alkaline phosphatase reaction was subsequently developed. This approach was tested in 22 patients with TGCT. In 14 patients (63.6%), double stained cells were found and thus the method was proven suitable for the detection of CIS cells in semen. In conclusion, transcription factors related to pluripotency and undifferentiated state of cells, which most likely have several variants or modifications, are unexpectedly detected using currently available antibodies in urogenital epithelial cells which may be shed into semen. Combining the immunohistochemical nuclear markers with a rapid cytochemical alkaline phosphatase reaction for detection of CIS cells in ejaculates may provide a more reliable diagnostic method.
Archive | 2002
F. E. von Eyben; Grete Krag Jacobsen; Lena Specht; Per Hyltoft Petersen; Ebbe Lindegård Madsen; Ole Blaabjerg; Mikael Rørth; H. von der Maase
The use of surveillance in patients with stage I testicular germ cell tumours is increasing internationally. The aim of this study was to elucidate pathological and clinical aspects of serum lactate dehydrogenase isoenzyme 1 catalytic concentration in this setting.
Archive | 2002
F. E. von Eyben; Grete Krag Jacobsen
Microinvasive testicular germ cell tumour (GCT) is defined as invasion of the interstitium by malignant germ cells without palpable tumour formation [1]. Microinvasive GCTs can also accompany overt tumours.
Nature Genetics | 2009
Anne Goriely; Ruth M. S. Hansen; Indira B. Taylor; Inge A. Olesen; Grete Krag Jacobsen; Simon J. McGowan; Susanne P. Pfeifer; Gilean McVean; Ewa Rajpert-De Meyts; Andrew O.M. Wilkie