EXPRESSION OF IMMUNOHISTOCHEMICAL MARKERS FOR TESTICULAR-CARCINOMA IN-SITU BY NORMAL HUMAN FETAL GERM-CELLS

BACKGROUND: It has been hypothesized that carcinoma in situ of the tes tis (CIS), which is the precursor of invasive testicular germ cell tum ours, may arise from fetal germ cells during fetal development rather than later in life. In order to corroborate this hypothesis, we undert ook the present study. EXPERIMENTAL DESIGN: Normal human germ cells fr om 10 first-trimester fetuses and 76 second- and third-trimester teste s were investigated for the immunohistochemical expression of the mark ers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental-like alkaline phosphatase, the protoo ncogene c-kit protein product, and the antigens for the monoclonal ant ibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells tha t demonstrated positive reaction with the markers were calculated. RES ULTS: The vast majority of the germ cells (75-100%) in the first-trime ster 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 fo r all the markers studied declined rapidly during the first part of th e second trimester, and the decrease continued with the fetal age. CON CLUSIONS: 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 explanatio n. However, we speculate that a transformation of normal fetal germ ce lls into CIS cells may take place before the end of the 9th week of fe tal development. Furthermore, the expression of c-kit in early human f etal germ cells indicates that the c-kit and its ligand play a role in the early human testicular development.