Reactivity of Germ Cell Maturation Stage-Specific Markers in Spermatocytic Seminoma: Diagnostic and Etiological Implications

Abstract

SUMMARY:It is generally accepted that testicular seminomas and spermatocytic seminomas have separate pathogeneses, although the origin of these two types of germ cell tumors of the adult testis remains a matter of debate. Although an embryonic germ cell origin seems to be most likely for seminomas, a spermatogonia-spermatocyte origin has been suggested for spermatocytic seminoma. To shed more light on the etiology of spermatocytic seminomas, we undertook an immunohistochemical and molecular approach using SCP1 (synaptonemal complex protein 1), SSX (synovial sarcoma on X chromosome), and XPA (xeroderma pigmentosum type A) as targets. Although a stage-specific expression pattern has been reported for SCP1 and SSX in normal spermatogenesis, we demonstrate here that it also exists for XPA. In fact, immunohistochemistry shows that the proteins of SCP1 and XPA are specifically present in the stage of primary and pachytene spermatocytes. In contrast, SSX was found in spermatogonia and primary spermatocytes, as well as in germ cells, from at least the 17th week of intrauterine development onward. Although no protein encoded by any of these genes was detected in tumor cells of a series of testicular seminomas, all tested spermatocytic seminomas were positive, in agreement with expression analysis. These data support the model that seminomas originate from an embryonic germ cell, and they imply that the cell of origin of spermatocytic seminomas is at least capable of maturing to the stage of spermatogonia-pachytene spermatocyte. (Lab Invest 2001, 81:919 -928).

Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization

“…Furthermore, it has been demonstrated that certain histologic types express markers associated with distinct maturational stages of germ cell development, which presumably are dependent on a specific gonadal environment. 7,[43][44][45] Lastly, there are some data suggesting that the chromosomal marker characteristic of testicular germ cell tumors, the isochromosome 12p, plays only a minor role in CNS-GCTs. 18,22 As a consequence, it must be debated whether the information generated in the more frequent (and more easily assessable) testicular germ cell tumors can indeed be transferred to CNS-GCTs without scrutiny.…”

VASA Is a Specific Marker for Both Normal and Malignant Human Germ Cells

“…In contrast, spermatocytic seminomas still exhibit similarities to cells belonging to the germ cell lineage (Burke and Mostofi, 1993;Cummings et al, 1994;Eble, 1994). They have a different etiology and clinical behavior from TGCT (Burke and Mostofi, 1993;Dekker et al, 1992;Looijenga et al, 1994;Rosenberg et al, 1998;Stoop et al, 2001). Available data suggest that spermatocytic seminomas originate from a later developmental stage of the germ cell than TGCT, most likely spermatocytes (Burke and Mostofi, 1993;Dekker et al, 1992;Eble, 1994;Muller et al, 1987;Romanenko and Persidskii, 1983;Rosai et al, 1969;Talerman, 1974Talerman, , 1980Talerman et al, 1984;).…”

“…However, we recently found indications that the cell of origin of spermatocytic seminoma might be at an earlier stage of development than spermatocytes. This cell is capable of further maturation and partial meiosis (Looijenga et al, 1994;Rosenberg et al, 1998;Stoop et al, 2001). …”

“…These tumors develop usually at a relatively advanced age, rarely metastasize, and are assumed to be derived from a later developmental stage of spermatogenesis (spermatocytes) than the precursor cells of TGCT (Burke and Mostofi, 1993;Eble, 1994;Muller et al, 1987;Romanenko and Persidskii, 1983;Rosai et al, 1969;Stoop et al, 2001;Talerman, 1974Talerman, , 1980Talerman et al, 1984). Their different pathogenesis from TGCT is also illustrated by the lack of glycogen (Mostofi and Sesterhenn, 1998), c-KIT, and GCAP/PLAP (Dekker et al, 1992), their positive staining for SSX, SCP1, and XPA (Stoop et al, 2001), as well as their unique chromosomal constitution (Looijenga et al, 1994;Rosenberg et al, 1998).…”

Origins and molecular biology of testicular germ cell tumors

“…Genetic studies on spermatocytic seminoma are few; it appears that the most common chromosomal abnormality is gains in chromosome 9. 2 A combined immunohistochemical and molecular study by Stoop et al 81 supports that these tumors are likely to originate in a cell farther along the developmental pathway than those that give rise to other germ cell tumors.…”