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

Author: Hoei-Hansen C.E.   Carlsen E.   Jorgensen N.   Leffers H.   Skakkebaek N.E.   Rajpert-De Meyts E.  

Publisher: Oxford University Press

ISSN: 1460-2350

Source: Human Reproduction, Vol.22, Iss.1, 2007-01, pp. : 167-173

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Abstract

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 [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-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, 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.

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