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[CD143 expression in testicular germ cell tumors]
F E Franke1, K Pauls, L Kerkman
1Institut für Pathologie, Justus-Liebig-Universität Giessen.
Abstract:
CD143 (angiotensin I-converting enzyme) occurs in two isoforms: a testicular form (tCD143) expressed during spermatogenesis, and a somatic form (sCD143) generally found in certain other cell types. To study these isoforms in normal and neoplastic germ cells of humans, we analyzed a broad collective of different testicular germ cell tumors (GCTs) of adults, adjacent intratubular germ cell neoplasms (IGCNs), and testicular tissues representing the regular germ cell development. Different techniques were employed on fresh frozen and formalin-fixed, paraffin-embedded tissues: CD143-mRNAs were analyzed by RT-PCR on selected cells after UV-laser-assisted cell picking and by in-situ hybridization using cRNA probes; the proteins were analyzed by semi-quantitative immunohistochemistry using monoclonal antibodies to CD143, and to PLAP/GCAP as controls. In contrast to normal germ cells bearing only tCD143 during spermiogenesis, both mRNA and protein of sCD143 were detected in neoplastic cells of all IGCNs and in the majority of seminomas. sCD143 expression also was found during testicular development, but was differently regulated in fetal germ cells and in GCTs compared with PLAP/GCAP. Thus, our findings (i) demonstrate profound changes in the expression of both CD143 isoforms during regular germ cell development and maturation, (ii) suspect sCD143 being involved in the regulation of germinal stem cell proliferation, (iii) are in agreement with the concept of an 'embryonic state' of neoplastic germ cells, (iv) indicate a close molecular relationship between IGCN and seminoma and, finally, (v) suggest sCD143 as an appropriate marker in the diagnosis of seminomas in addition to PIAP/GCAP.
Insights
Somatic CD143 (sCD143) is found in human testicular germ cell tumors, unlike normal germ cells which only express the testicular form (tCD143). This suggests sCD143 may be involved in germ cell proliferation and useful for diagnosing seminomas.
Area of Science:
- Molecular biology
- Oncology
- Reproductive biology
Context:
- CD143 (angiotensin I-converting enzyme) exists as testicular (tCD143) and somatic (sCD143) isoforms.
- tCD143 is expressed during spermatogenesis, while sCD143 is found in other cell types.
- Germ cell tumors (GCTs) and intratubular germ cell neoplasms (IGCNs) are studied in adult humans.
Purpose:
- To investigate the expression of CD143 isoforms in normal and neoplastic human germ cells.
- To analyze CD143 isoform expression during germ cell development and in various testicular cancers.
Summary:
- Both mRNA and protein for sCD143 were detected in neoplastic cells of IGCNs and most seminomas, contrasting with normal germ cells expressing only tCD143.
- sCD143 expression patterns differed in fetal germ cells and GCTs compared to PLAP/GCAP.
- The study employed RT-PCR, in-situ hybridization, and immunohistochemistry on various testicular tissues.
Impact:
- Demonstrates significant changes in CD143 isoform expression during germ cell development and maturation.
- Suggests sCD143 involvement in germinal stem cell proliferation and supports the 'embryonic state' concept for neoplastic germ cells.
- Indicates a molecular link between IGCN and seminoma, proposing sCD143 as a potential diagnostic marker for seminomas alongside PLAP/GCAP.