Embryonal carcinoma is a histologic subgroup of testicular germ cell
tumors (TGCTs), and its cells may follow differentiation lineages in a
manner similar to early embryogenesis. To acquire new knowledge about
the transcriptional programs operating in this tumor development model,
we used 22k oligo DNA microarrays to analyze normal and neoplastic
tissue samples from human testis. Additionally, retinoic acid–induced in vitro
differentiation was studied in relevant cell lines. We identified genes
characterizing each of the known histologic subtypes, adding up to a
total set of 687 differentially expressed genes. Among these, there was a
significant overrepresentation of gene categories, such as genomic
imprinting and gene transcripts associated to embryonic stem cells.
Selection for genes highly expressed in the undifferentiated embryonal
carcinomas resulted in the identification of 58 genes, including
pluripotency markers, such as the homeobox genes NANOG and POU5F1 (OCT3/4), as well as GAL, DPPA4, and NALP7.
Interestingly, abundant expression of several of the pluripotency genes
was also detected in precursor lesions and seminomas. By use of tissue
microarrays containing 510 clinical testicular samples, GAL and POU5F1
were up-regulated in TGCT also at the protein level and hence validated
as diagnostic markers for undifferentiated tumor cells. The present
study shows the unique gene expression profiles of each histologic
subtype of TGCT from which we have identified deregulated components in
selected processes operating in normal development, such as WNT
signaling and DNA methylation.