Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers.
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-2gamma [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-2gamma-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-2gamma, 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.
Hoei-Hansen
C E
CE
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. chh@dadlnet.dk
Carlsen
E
E
Jorgensen
N
N
Leffers
H
H
Skakkebaek
N E
NE
Rajpert-De Meyts
E
E
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000175:diagnosis; D004268:DNA-Binding Proteins / Q000032:analysis; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis*; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D011237:Predictive Value of Tests; D012661:Semen / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013736:Testicular Neoplasms / Q000175:diagnosis*; D050656:Transcription Factor AP-2 / Q000032:analysis
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007527:Isoenzymes; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D050656:Transcription Factor AP-2; C055791:germ-cell AP isoenzyme; D000469:Alkaline Phosphatase