Recent developments in testicular germ cell tumor research

Abstract

Testicular germ cell tumors of adolescents and adults (TGCTs; the so-called type II variant) are the most frequent malignancies found in Caucasian males between 20 and 40 years of age. The incidence has increased over the last decades. TGCTs are divided into seminomas and nonseminomas, the latter consisting of the subgroups embryonal carcinoma, yolk-sac tumor, teratoma, and choriocarcinoma. The pathogenesis starts in utero, involving primordial germ cells/gonocytes that are blocked in their differentiation, and develops via the precursor lesion carcinoma in situ toward invasiveness. TGCTs are totipotent and can be considered as stem cell tumors. The developmental capacity of their cell of origin, the primordial germ cells/gonocyte, is demonstrated by the different tumor histologies of the invasive TGCTs. Seminoma represents the germ cell lineage, and embryonal carcinoma is the undifferentiated component, being the stem cell population of the nonseminomas. Somatic differentiation is seen in the teratomas (all lineages), whereas yolk-sac tumors and choriocarcinoma represent extra-embryonal differentiation. Seminomas are highly sensitive to irradiation and (DNA damaging) chemotherapy, whereas most nonseminomatous elements are less susceptible to radiation, although still sensitive to chemotherapy, with the exception of teratoma. To allow early diagnosis and follow up, appropriate markers are mandatory to discriminate between the different subgroups. In this review, a summary will be given related to several recent developments in TGCT research, especially selected because of their putative clinical impact.

DNA methyltransferase-3 like protein expression in various histological types of testicular germ cell tumor

“…Three of the pure YST cases were prepubertal. It is well-known that prepubertal YST and prepubertal teratomas are classified as different entities as type I GCT from adult seminoma and NSGCT (type II GCT) (5). In the present study, four of the five prepubertal pure teratomas were positively stained for DNMT3L, but the finding was not specific to the prepubertal cases.…”

“…Moreover, ECs also expressed CD30 and SOX2, both of which are also known to play a significant role in the regulation of pluripotency (3,4). With expression profiles resembling those of embryonic stem cells, ECs are known to be able to further differentiate into yolk sac tumor (YST), choriocarcinoma (CC) and teratoma (5).…”

Nodal/Cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors

“…These tumors often arise at extra-gonadal locations such as the neck, midline brain and retroperitoneum, presumably because the transformation occurs as the PGCs are migrating towards the gonads during embryonic development (van de Geijn et al 2009).…”

“…TGCTs of Type II do not develop until after puberty and can be further divided into two sub-groups: seminomas (SE) and non-seminomas (NS), both of which display many markers of both fetal germ cells and pluripotency ( Fig. 1) (Sonne et al 2009;van de Geijn et al 2009). Seminomas are characterised by germ cell-like gene expression and are the least-invasive Type II germ cell tumor.…”

“…The TGCTs described above are distinct from somatic cancers for two important reasons: Firstly, NS can differentiate into somatic, germ and extra-embryonic cell lineages and therefore is considered the only known totipotent solid cancer (Honecker et al 2006;van de Geijn et al 2009). Secondly, the cell of origin or 'cancer stem cell', CIS, is commonly assumed to originate during early fetal development from a germ cell in an undifferentiated environment (as opposed to the differentiated, adult tissue that most solid somatic cancers arise within) (reviewed by (Kristensen et al 2008)).…”