March 1, 2007

Towards A Non-Invasive Method For Early Detection Of Testicular Neoplasia In Semen Samples By Identification Of Fetal Germ Cell-Specific Markers Testicular germ cell tumors (TGCTs) originate from a common
precursor, carcinoma in situ (CIS). The authors present an approach to detect CIS cells in the ejaculate using primordial germ cell/gonocyte as markers. Primordial germ cells were stained utilizing Immunocytological staining for AP-2[gamma] and/or OCT-3/4, NANOG or placental alkaline phosphatase (PLAP)].

Semen was stained from 294 infertile patients and 209 patient's testicular germ cell tumors. 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]. NANOG and PLAP were not suitable. The assay sensitivity for participants with CIS was 54.5% and greater than that for patients with tumors.  Assay specificity was 93.6%, positive predictive value (PPV) 83.3% and negative predictive value (NPV) 60.3%.

The authors concluded that this technique was Immunocytological semen analysis based on expression of fetal germ cell markers in exfoliated cells has auxiliary diagnostic value. However, a negative test does not exclude tumor.

  Editorial Comment

The testicular CIS issue is extremely interesting. This article is from Scandinavia and the life time risk for CIS in Denmark has been reported to be 1% which is the same as the risk of TGCT's. There appears to be significant regional variation in the incidence of testicular cancer. The age of standardized incidence in Denmark was 15.2 per 100,000. CIS is believed to be the precursor for TGCT. In spite of the high rate of curing TGCT, the opportunity to diagnose or have an adjunctive test for NSTG cell tumors in high risk individual (prior testicular tumors, cryptorchidism etc) is very appealing. Such a test may be of particular importance as we gain further experience with having longer follow-up with testes sparing surgery for small carcinomas. As the authors concluded, "further effort is needed to improve this assay, forВ example, by employing a more sensitive biochemical method of detection."

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

Human Reproduction: 22(1):167-173, January 2007

Reviewed by Contributing Editor Harris M. Nagler, MD

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