Jørgensen N, Rajpert-De Meyts E, Graem N, Müller J, Giwercman A, Skakkebaek N E
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Lab Invest. 1995 Feb;72(2):223-31.
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.
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.
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.
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.
有假说认为，睾丸原位癌（CIS）作为浸润性睾丸生殖细胞肿瘤的前体，可能起源于胎儿发育过程中的胎儿生殖细胞，而非在生命后期产生。为了证实这一假说，我们开展了本研究。
对来自10例孕早期胎儿和76例孕中期及孕晚期睾丸的正常人类生殖细胞进行睾丸原位癌标志物的免疫组化表达研究。研究中使用的标志物组合包括胎盘样碱性磷酸酶、原癌基因c-kit蛋白产物以及单克隆抗体TRA-1-60和M2A的抗原。计算与这些标志物呈阳性反应的胎儿生殖细胞的相对数量。
孕早期性腺中绝大多数生殖细胞（75%-100%）对胎盘样碱性磷酸酶、TRA-1-60和M2A呈阳性。在10例孕早期性腺中有3例检测到c-kit蛋白。在孕中期的第一阶段，所有研究标志物呈阳性的生殖细胞相对数量迅速下降，且随着胎龄增加持续减少。
正常胎儿生殖细胞中成人原位癌标志物的表达与CIS细胞可能起源于胎儿生殖细胞的假说一致，尽管产后发生的CIS细胞中抗原的重新表达可能提供另一种解释。然而，我们推测正常胎儿生殖细胞向CIS细胞的转变可能发生在胎儿发育第9周结束之前。此外，c-kit在早期人类胎儿生殖细胞中的表达表明c-kit及其配体在早期人类睾丸发育中起作用。
