Maturation delay of germ cells in fetuses with trisomy 21 results in increased risk for the development of testicular germ cell tumors

Cools, Martine; Honecker, Friedemann; Stoop, Hans; Veltman, Joris D.; de Krijger, Ronald R.; Steyerberg, Ewout; Wolffenbuttel, Katja P.; Bokemeyer, Carsten; Lau, Yun-Fai Chris; Drop, Stenvert L.S.; Looijenga, Leendert H.J.

doi:10.1016/j.humpath.2005.09.021

« Previous Next »Human Pathology
Volume 37, Issue 1 , Pages 101-111, January 2006

Maturation delay of germ cells in fetuses with trisomy 21 results in increased risk for the development of testicular germ cell tumors☆

Martine Cools, MD
- Department of Pathology, Josephine Nefkens Institute, Erasmus MC–University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands
Friedemann Honecker, MD
- Department of Pathology, Josephine Nefkens Institute, Erasmus MC–University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands
- Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Hans Stoop, BSc
- Department of Pathology, Josephine Nefkens Institute, Erasmus MC–University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands
Joris D. Veltman, BSc
- Department of Pathology, Josephine Nefkens Institute, Erasmus MC–University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands
Ronald R. de Krijger, MD, PhD
- Department of Pathology, Josephine Nefkens Institute, Erasmus MC–University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands
Ewout Steyerberg, PhD
- Department of Public Health, Center for Clinical Decision Science, Erasmus MC–University Medical Center, 3000 DR Rotterdam, The Netherlands
Katja P. Wolffenbuttel, MD
- Department of Pediatric Urology, Sophia Children's Hospital, Erasmus MC–University Medical Center, 3000 DR Rotterdam, The Netherlands
Carsten Bokemeyer, MD, PhD
- Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Yun-Fai Chris Lau, PhD
- Division of Cell and Developmental Genetics, Department of Medicine, VA Medical Center, University of California, San Francisco, CA 94121, USA
Stenvert L.S. Drop, MD, PhD
- Department of Pediatric Endocrinology, Sophia Children's Hospital, Erasmus MC–University Medical Center, 3000 DR Rotterdam, The Netherlands
Leendert H.J. Looijenga, PhD
- Department of Pathology, Josephine Nefkens Institute, Erasmus MC–University Medical Center, Daniel den Hoed, 3000 DR Rotterdam, The Netherlands
- Corresponding author.

Received 29 March 2005; accepted 24 September 2005.

Summary

Trisomy 21 is associated with an increased risk for the occurrence of germ cell tumors in males. The development of these tumors is thought to be related to events in fetal life. A delay in the maturation of germ cells is one of the mechanisms that have been proposed for the development of these tumors in high-risk groups such as intersex patients. To investigate whether a delay in germ cell development also occurs in trisomy 21, we examined the gonads of 30 fetuses, neonates, and infants with trisomy 21 (19 males and 11 females) for the expression of several immunohistochemical germ cell markers throughout pregnancy and compared them with a series of 46 age-matched controls. The results of our study reveal a significant delay in germ cell development in fetuses with trisomy 21, especially in males. Prolonged expression of octamer binding transcription factor 3/4, in combination with an increased expression of testis-specific protein, Y-encoded, might have pathogenetic relevance for the development of testicular germ cell tumors in this population.

Keywords: Trisomy 21, Gonadal development, Germ cell neoplasia, OCT3/4, TSPY

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☆ This study was financially supported by the ESPE Research Fellowship which is sponsored by Novo Nordisk (Copenhagen, Denmark), the Deutsche Krebshilfe (Bonn, Germany), and the Dutch Cancer Society (Amsterdam, The Netherlands).

PII: S0046-8177(05)00536-8

doi:10.1016/j.humpath.2005.09.021

« Previous Next »Human Pathology
Volume 37, Issue 1 , Pages 101-111, January 2006

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