Gene expression profiling identifies new biological markers of neoplastic germ cells.
BACKGROUND
There is only limited knowledge about gene expression in human testicular germ cell tumors of adolescents and adults (TGCTs), and, in particular in its preinvasive stage intratubular germ cell neoplasia unclassified (IGCNU).


METHODS
Global gene expression was studied in 10 invasive human testicular germ cell tumors (TGCTs), 7 intratubular germ cell neoplasia unclassified (IGCNU) and 3 normal testes. The pattern of expression of several genes was studied by immunohistochemistry on tissue microarrays containing 126 TGCTs, IGCNU, normal testes and in 5 fetal testes.


RESULTS
RAS-related genes (KRAS2, RALA, RAB39B) and various core markers of embryonic stem cells were overexpressed in IGCNU compared to normal testes. CD9, PODXL and centromere-specific histone-H3-like protein CENPA were specifically identified in IGCNU, seminomas, embryonal carcinomas and in fetal gonocytes. Embryonic stem cell regulator SOX2 and downstream targets of the Nodal pathway were up-regulated in embryonal carcinoma only but not in IGCNU/seminoma. Preliminary data revealed that the expression profile of IGCNU is dependent on the histology of the adjacent invasive tumor.


CONCLUSIONS
Our study determined the genes involved in early pathogenetic events of neoplastic germ cell formation, provided new insights into genetic pathways driving the transition of embryonal carcinoma and seminoma from IGCNU and identified new biomarkers of neoplastic germ cells such as CD9, CENPA and PODXL.
Biermann
Katharina
K
Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. katharina.biermann@ukb.uni-bonn.de
Heukamp
Lukas Carl
LC
Steger
Klaus
K
Zhou
Hui
H
Franke
Folker Ernst
FE
Guetgemann
Ines
I
Sonnack
Violetta
V
Brehm
Ralph
R
Berg
Johannes
J
Bastian
Patrick Jan
PJ
Müller
Stefan Cajetan
SC
Wang-Eckert
Lihua
L
Schorle
Hubert
H
Büttner
Reinhard
R
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D004273:DNA, Neoplasm