About this Journal Submit a Manuscript Table of Contents
International Journal of Endocrinology
Volume 2012 (2012), Article ID 671209, 9 pages
http://dx.doi.org/10.1155/2012/671209
Research Article

Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors

1Department of Pathology, Erasmus MC-University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
2Centre for Reproduction and Development, Monash Institute of Medical Research, Melbourne, VIC, Australia
3Department of Pediatric Endocrinology, Erasmus MC-University Medical Center Rotterdam, Sophia, Rotterdam, The Netherlands
4Department of Radiation Oncology, Erasmus MC-University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
5Department of Pediatric Urology, Erasmus MC-University Medical Center Rotterdam, Sophia, Rotterdam, The Netherlands

Received 11 August 2011; Revised 27 September 2011; Accepted 13 October 2011

Academic Editor: Rodolfo Rey

Copyright © 2012 Remko Hersmus et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. I. A. Hughes, C. Houk, S. F. Ahmed, and P. A. Lee, “Consensus statement on management of intersex disorders,” Archives of Disease in Childhood, vol. 91, no. 7, pp. 554–563, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. D. C. Page, “Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads,” Development, vol. 101, supplement, pp. 151–155, 1987. View at Scopus
  3. M. Cools, S. L. S. Drop, K. P. Wolffenbuttel, J. W. Oosterhuis, and L. H. J. Looijenga, “Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers,” Endocrine Reviews, vol. 27, no. 5, pp. 468–484, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. J. W. Oosterhuis and L. H. J. Looijenga, “Testicular germ-cell tumours in a broader perspective,” Nature Reviews Cancer, vol. 5, no. 3, pp. 210–222, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. M. M. Grumbach, I. A. Hughes, and F. A. Conte, “Disorders of sex differentiation,” in Williams Textbook of Endocrinology, P. R. Larsen, H. M. Kronenberg, and S. Melmed, Eds., pp. 842–1002, WB Saunders, Philadelphia, Pa, USA, 2003.
  6. L. H. J. Looijenga, R. Hersmus, A. J. M. Gillis et al., “Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene,” Cancer Research, vol. 66, no. 1, pp. 290–302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Hersmus, N. Kalfa, B. de Leeuw et al., “FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD),” Journal of Pathology, vol. 215, no. 1, pp. 31–38, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Cools, H. Stoop, A. M. F. Kersemaekers et al., “Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic gonads,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 6, pp. 2404–2413, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Hersmus, B. H. C. G. M. de Leeuw, K. P. Wolffenbuttel et al., “New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD),” Molecular and Cellular Endocrinology, vol. 291, no. 1-2, pp. 1–10, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. Y. F. C. Lau, P. M. Chou, J. C. Iezzoni, J. A. Alonzo, and L. G. Kömüves, “Expression of a candidate gene for the gonadoblastoma locus in gonadoblastoma and testicular seminoma,” Cytogenetics and Cell Genetics, vol. 91, no. 1–4, pp. 160–164, 2000. View at Scopus
  11. A. M. F. Kersemaekers, F. Honecker, H. Stoop et al., “Identification of germ cells at risk for neoplastic transformation in gonadoblastoma: an immunohistochemical study for OCT3/4 and TSPY,” Human Pathology, vol. 36, no. 5, pp. 512–521, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Bray, L. Richiardi, A. Ekbom, E. Pukkala, M. Cuninkova, and H. Møller, “Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality,” International Journal of Cancer, vol. 118, no. 12, pp. 3099–3111, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. N. E. Skakkebæk, E. Rajpert-De Meyts, and K. M. Main, “Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects,” Human Reproduction, vol. 16, no. 5, pp. 972–978, 2001. View at Scopus
  14. O. Akre and L. Richiardi, “Does a testicular dysgenesis syndrome exist?” Human Reproduction, vol. 24, no. 9, pp. 2053–2060, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. E. A. Rapley, C. Turnbull, A. A. Al Olama et al., “A genome-wide association study of testicular germ cell tumor,” Nature Genetics, vol. 41, no. 7, pp. 807–810, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. P. A. Kanetsky, N. Mitra, S. Vardhanabhuti et al., “Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer,” Nature Genetics, vol. 41, no. 7, pp. 811–815, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. P. J. Woodward, A. Heidenreich, L. H. J. Looijenga, et al., “Testicular germ cell tumors,” in World Health Organization Classification of Tumours Pathology and Genetics of the Urinary System and Male Genital Organs, J. N. Eble, G. Sauter, J. I. Epstein, et al., Eds., pp. 217–278, IARC Press, Lyon, France, 2004.
  18. F. Honecker, H. Stoop, R. R. de Krijger, Y. F. C. Lau, C. Bokemeyer, and L. H. J. Looijenga, “Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells,” Journal of Pathology, vol. 203, no. 3, pp. 849–857, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. H. Stoop, F. Honecker, M. Cools, R. de Krijger, C. Bokemeyer, and L. H. J. Looijenga, “Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study,” Human Reproduction, vol. 20, no. 6, pp. 1466–1476, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. T. Kido and Y. F. C. Lau, “A Cre gene directed by a human TSPY promoter is specific for germ cells and neurons,” Genesis, vol. 42, no. 4, pp. 263–275, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. D. Bissett, L. Kunkeler, L. Zwanenburg et al., “Long-term sequelae of treatment for testicular germ cell tumours,” British Journal of Cancer, vol. 62, no. 4, pp. 655–659, 1990. View at Scopus
  22. M. A. Malik, Z. Iqbal, K. M. Chaudri, N. A. Malik, and A. J. Ahmed, “Crossed testicular ectopia,” Urology, vol. 71, no. 5, pp. 984–986, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. R. E. Scully, “Gonadoblastoma. A review of 74 cases,” Cancer, vol. 25, no. 6, pp. 1340–1356, 1970. View at Scopus
  24. J. Kehler, E. Tolkunova, B. Koschorz et al., “Oct4 is required for primordial germ cell survival,” The EMBO Reports, vol. 5, no. 11, pp. 1078–1083, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. F. Schnieders, T. Dörk, J. Arnemann, T. Vogel, M. Werner, and J. Schmidtke, “Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues,” Human Molecular Genetics, vol. 5, no. 11, pp. 1801–1807, 1996. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Li, Z. L. Tabatabai, T. L. Lee et al., “The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors,” Human Pathology, vol. 38, no. 10, pp. 1470–1481, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. S. W. Oram, X. X. Liu, T. L. Lee, W. Y. Chan, and Y. F. C. Lau, “TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells,” BMC Cancer, vol. 6, article 154, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Stoop, F. Honecker, G. J. M. van de Geijn et al., “Stem cell factor as a novel diagnostic marker for early malignant germ cells,” Journal of Pathology, vol. 216, no. 1, pp. 43–54, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Shahid, V. S. Dhillon, H. S. Khalil et al., “A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient,” BMC Medical Genetics, vol. 11, no. 1, article 131, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. B. Isidor, C. Capito, F. Paris et al., “Familial frameshift SRY mutation inherited from a mosaic father with testicular dysgenesis syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 9, pp. 3467–3471, 2009. View at Publisher · View at Google Scholar · View at Scopus