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Hum. Reprod. Advance Access originally published online on August 18, 2006
Human Reproduction 2007 22(1):167-173; doi:10.1093/humrep/del320
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers

C.E. Hoei-Hansen1, E. Carlsen, N. Jorgensen, H. Leffers, N.E. Skakkebaek and E. Rajpert-De Meyts

University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark

1 To whom correspondence should be addressed at: University Department of Growth and Reproduction (GR-5064), Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: chh{at}dadlnet.dk

BACKGROUND: Testicular germ cell tumours (TGCTs) originate from a common precursor, carcinoma in situ (CIS). Diagnosis at the CIS stage is desirable as it minimizes the necessary treatment. A detailed clinical evaluation of an approach to detect CIS cells in the ejaculate using primordial germ cell/gonocyte markers is presented. METHODS: Immunocytological staining for AP-2{gamma} [and in some cases, OCT-3/4, NANOG or placental alkaline phosphatase (PLAP)] was performed in semen samples from 294 infertile patients and 209 patients with TGCTs or other diseases. RESULTS: Presence of AP-2{gamma}-stained cells was detected in 50% of participants with CIS and in 33.9% of TGCT patients before treatment (non-seminomas: 56.6%, seminomas: 17.4%). OCT-3/4 results were similar to those of AP-2{gamma}, whereas NANOG and PLAP stainings were unsuitable. Sensitivity was 54.5% for participants harbouring pre-invasive CIS but reduced in participants with overt TGCTs, perhaps because of obstruction. Assay specificity was 93.6%, positive predictive value (PPV) 83.3% and negative predictive value (NPV) 60.3%. CONCLUSIONS: Immunocytological semen analysis based on expression of fetal germ cell markers in exfoliated cells has auxiliary diagnostic value, as it detects some patients with CIS/incipient tumour, but a negative result does not exclude TGCT. Further effort is needed to improve this assay, for example, by employing a more sensitive biochemical method of detection.

Key words: AP-2{gamma}/carcinoma in situ/intratubular germ cell neoplasia/OCT-3/4/testicular germ cell tumour


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