The immunohistochemical expression pattern of Chk2, p53, p19INK4d,MAGE-A4 and other selected antigens provides new evidence for the premeiotic origin of spermatocytic seminoma

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.