Rajpert-De Meyts E, Jørgensen N, Brøndum-Nielsen K, Müller J, Skakkebaek N E
Department of Growth and Reproduction, Copenhagen University and Rigshospitalet, Denmark.
APMIS. 1998 Jan;106(1):198-204; discussion 204-6. doi: 10.1111/j.1699-0463.1998.tb01336.x.
Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We hypothesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differentiation arrest which may render them susceptible to neoplastic transformation. Morphologically homogenous premalignant carcinoma in situ (CIS) cells have the potential to differentiate into a variety of histological forms of overt testicular tumours. Analysis of cell surface antigens expressed by CIS cells found in the vicinity of pure and mixed tumours demonstrates that CIS cells are phenotypically heterogeneous. Comparison of the phenotypes of CIS cells, primordial germ cells, human embryonal carcinoma cells and closely related primate embryonal stem cells reveals various similarities but also differences. We speculate that phenotypical heterogeneity of CIS cells may be associated with their potential to give rise to different tumour types, and may be related to the developmental stage of the early germ cell which has undergone malignant transformation.
临床观察和流行病学证据表明，导致男性生殖细胞发生肿瘤转化的重要病因病理事件可能发生在胎儿期或婴儿早期。在性腺发育和性分化存在各种障碍的个体中，如性腺发育不全或雄激素不敏感综合征，生殖细胞瘤的发病率很高。在患有21三体综合征、特发性不育症和低出生体重的个体中也发现风险增加。不育症有时与性染色体的小畸变有关（例如低频嵌合体XY/XO），这在睾丸癌患者中也能发现。多种易患睾丸肿瘤的情况以及许多国家其发病率的上升表明环境因素的影响，这些因素可能会影响具有遗传易感性的个体。我们推测，如果睾丸发育受到干扰或延迟，原始生殖细胞或生殖母细胞会经历成熟延迟或分化停滞，这可能使它们易发生肿瘤转化。形态学上同质的原位癌前癌细胞（CIS）有潜力分化为各种组织学类型的显性睾丸肿瘤。对在纯肿瘤和混合肿瘤附近发现的CIS细胞表达的细胞表面抗原的分析表明，CIS细胞在表型上是异质的。对CIS细胞、原始生殖细胞、人胚胎癌细胞和密切相关的灵长类胚胎干细胞的表型进行比较，发现了各种相似之处，但也存在差异。我们推测，CIS细胞的表型异质性可能与其产生不同肿瘤类型的潜力有关，并且可能与经历恶性转化的早期生殖细胞的发育阶段有关。
