title: Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells.
abstract: BACKGROUND
  It has been hypothesized that carcinoma in situ of the testis (CIS), which is the precursor of invasive testicular germ cell tumours, may arise from fetal germ cells during fetal development rather than later in life. In order to corroborate this hypothesis, we undertook the present study.
  
  
  METHODS
  Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated.
  
  
  RESULTS
  The vast majority of the germ cells (75-100%) in the first-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester, and the decrease continued with the fetal age.
  
  
  CONCLUSIONS
  The expression of adult carcinoma in situ markers in normal fetal germ cells is consistent with the hypothesis that CIS cells may arise from fetal germ cells, although re-expression of the antigens in postnatally arising CIS cells could provide an alternative explanation. However, we speculate that a transformation of normal fetal germ cells into CIS cells may take place before the end of the 9th week of fetal development. Furthermore, the expression of c-kit in early human fetal germ cells indicates that the c-kit and its ligand play a role in the early human testicular development.
authors.affiliation: University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Jørgensen
authors.forename: E
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.forename: N
authors.initials: N
authors.lastname: Graem
authors.forename: J
authors.initials: J
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Giwercman
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000175:diagnosis / Q000196:embryology; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis; D013736:Testicular Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000196:embryology; D013737:Testis / Q000737:chemistry / Q000166:cytology* / Q000196:embryology / Q000201:enzymology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; C055791:germ-cell AP isoenzyme; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D000469:Alkaline Phosphatase