Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. A Polygenic Risk Score Suggests Shared Genetic Architecture of Voice Break With Early Markers of Pubertal Onset in Boys

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Bone mineral density is preserved in men with idiopathic infertility

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. CENTRAL PRECOCIOUS PUBERTY IN TWO BOYS WITH PRADER-WILLI SYNDROME ON GROWTH HORMONE TREATMENT

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Author Correction: Characterisation and localisation of the endocannabinoid system components in the adult human testis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCTs that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCTs occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCTs. The rare spermatocytic tumour of older men is derived from post-pubertal germ cells that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative markers for GCT, except teratoma, are genes expressed in primordial germ cell/gonocyte and embryonic pluripotency-related, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2g (TFAP2C) and LIN28. These genes are not expressed in normal adult germ cells, hence are useful immunohistochemical markers for GCNIS and GCT subtypes in tissue specimens. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNAs (miRs). Testicular GCTs display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are currently under development and hold a great promise for the future. In some patients miR-based tests may be even more sensitive than the classical serum tumour markers, beta chorio-gonadotrophin (β-hCG), α-fetoprotein (AFP) and lactate dehydrogenase (LDH), which are currently used in the clinic. In summary, research advances have provided clinicians with a panel of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up.

Original languageEnglish
JournalFolia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society
Volume53
Issue number3
Pages (from-to)177-88
DOIs
Publication statusPublished - 26 Aug 2015

ID: 45598363