AIMS: Spermatocytic seminoma is a rare germ cell derived tumour of the testis that occurs mainly in older men. We analysed the expression of recently discovered markers for germ cell differentiation and the mitosis-meiosis transition in order to define the antigen profile for diagnostic purposes and to clarify the biology and histogenesis of spermatocytic seminoma. METHODS AND RESULTS: Twenty-five spermatocytic seminomas were examined for immunohistochemical expression of germ cell-specific onco-fetal antigens and proteins involved in regulation of germ cell division, DNA repair and differentiation. The panel included Chk2, p19INK4d, p53, MAGE-A4, KIT, TRA-1-60, neurone-specific enolase and placental-like alkaline phosphatase. Four of these proteins/antigens have never before been investigated in spermatocytic seminoma. Proteins highly expressed in gonocytes and spermatogonia, such as Chk2, MAGE-A4 and neurone-specific enolase, were consistently present in spermatocytic seminoma. Antigens expressed in embryonic germ cells but not in the normal adult testis, e.g. TRA-1-60, were undetectable, with the exception of p53 protein, which was demonstrated in 80% of cases. A proto-oncogene p19INK4d, which is involved in the transition from mitotic to meiotic division in germ cells, was not detected in spermatocytic seminoma. CONCLUSIONS: The investigation provided new information concerning the expression of Chk2, MAGE-A4, neurone-specific enolase and p19INK4d in spermatocytic seminoma. The pattern of expression is highly consistent with the origin of spermatocytic seminoma from a premeiotic germ cell, which has lost embryonic traits and has committed to spermatogenic lineage but has not yet passed the meiotic checkpoint, most probably from the spermatogonium of the adult testis.
- MeSH
- antigeny nádorové metabolismus MeSH
- checkpoint kinasa 2 MeSH
- dospělí MeSH
- fosfopyruváthydratasa metabolismus MeSH
- imunoenzymatické techniky MeSH
- inhibitor p16 cyklin-dependentní kinasy metabolismus MeSH
- inhibitor p19 cyklin-dependentní kinasy MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * metabolismus MeSH
- nádorové proteiny * metabolismus MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- protein-serin-threoninkinasy * MeSH
- proteinkinasy metabolismus MeSH
- proteiny buněčného cyklu * MeSH
- seminom etiologie metabolismus patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- testikulární nádory etiologie metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
This review summarises the existing knowledge on the phenotype of the carcinoma in situ (CIS) cell. CIS is a common pre-invasive precursor of testicular germ cell tumours of adolescents and young adults. These tumours display a variety of histological forms. Classical seminoma proliferates along the germ cell lineage, whereas embryonal carcinoma retains embryonic features and readily differentiates into teratomas that resemble various somatic cell lineages. A thorough review of the gene expression in CIS cells in comparison to normal testicular germ cells and overt tumours supports the view that CIS is a common precursor for both tumour types. Impaired cell differentiation resulting in a partial retention of the embryonic features, associated with an increasing genomic instability may be responsible for a remarkable phenotypic heterogeneity of CIS cells. Depending on the degree of differentiation and pluripotency, CIS cells found in adult patients seem to be predestined for further malignant progression into one or the other of the two main types of overt tumours. A new concept of phenotypic continuity of differentiation of germ cells along germinal lineage with a gradual loss of embryonic features based on the analysis of gene expression in all types of germ cells during their ontogeny is presented in this review. The data point out that despite the phenotypic continuum of gene expression, there are two periods of rapid changes of gene expression: first at the transition from primordial germ cells to pre-spermatogonia, and later during the pubertal switch from the mitotic to meiotic cell division. The persistent expression of embryonic traits in CIS cells, and the high expression of the cell cycle regulators that are typical of mitotic germ cells support our long-standing hypothesis that CIS cells originate from primordial germ cells or gonocytes and not from germ cells in the adult testis.
- MeSH
- antigeny nádorové genetika MeSH
- buněčný cyklus genetika MeSH
- dospělí MeSH
- exprese genu MeSH
- fenotyp * MeSH
- imunohistochemie MeSH
- karcinom in situ * genetika patologie MeSH
- kmenové buňky patologie MeSH
- lidé MeSH
- lidské chromozomy X genetika MeSH
- lidský chromozom Y genetika MeSH
- mladiství MeSH
- nádorová transformace buněk genetika MeSH
- oprava DNA MeSH
- seminom * genetika patologie MeSH
- spermie patologie MeSH
- testikulární nádory * genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Klíčová slova
- amplituda potencionálu zrakového, amplituda vyvolaného okcipitálního potencionálu,
- MeSH
- elektroencefalografie * MeSH
- lidé MeSH
- retina MeSH
- stroboskopie * MeSH
- světelná stimulace MeSH
- Check Tag
- lidé MeSH