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  • Review Article
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Testicular germ-cell tumours in a broader perspective

Nature Reviews Cancer volume 5, pages 210–222 (2005)Cite this article

Key Points

  • Germ-cell tumours (GCTs) of all anatomical sites can be classified into five groups, characterized by their chromosomal complement and developmental potential.

  • The most significant recurrent chromosomal aberrations in type I yolk-sac tumours are loss of 1p, 4 and 6q, and gain of 1q, 12(p13) and 20q. In type II seminomas and non-seminomatous GCTs, the most significant recurrent chromosomal aberrations are gain of 7, 8, 12p, 21 and X, and loss of chromosomes 1p, 11, 13 and 18. Aberrations of 12p are the only recurrent structural abnormalities in type II GCTs. In type III spermatocytic seminomas, gain of chromosome 9 is most common.

  • The originating cell is most probably a primitive germ cell of which the developmental potential differs according to its stage of maturation and pattern of genomic imprinting.

  • Animal models are available for the different groups of GCTs, except for the type II seminomas and non-seminomatous GCTs.

  • An activating KIT mutation in codon 816 is an early pathogenetic event in bilateral testicular seminomas and non-seminomatous GCTs.

  • The transcription factor OCT3/4, a characteristic of primordial germ cells and pluripotent stem cells, is a new and robust diagnostic marker for type II seminomas and non-seminomatous GCTs, including their intratubular precursor.

  • Treatment sensitivity and resistance of GCTs probably correlates with retention and loss of embryonic characteristics (in particular, DNA-repair deficiency), respectively.

Abstract

The germ-cell tumours are a fascinating group of neoplasms because of their unusual biology and the spectacular therapeutic results that have been obtained in these tumours. Traditionally, this group of neoplasms is presented in an organ-oriented approach. However, recent clinical and experimental data convincingly demonstrate that these neoplasms are one disease with separate entities that can manifest themselves in different anatomical sites. We propose five entities, in which the developmental potential is determined by the maturation stage and imprinting status of the originating germ cell. Recent progress begins to explain the apparent unpredictable development of germ-cell tumours and offers a basis for understanding their exquisite sensitivity to therapy.

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Figure 1: Schematic representation of normal embryonic development and origin of the germ-cell lineage.
Figure 2: Schematic representation of the supposed origin of the various types of germ-cell tumour.
Figure 3: Characteristic differences between normal germ-cell development and formation of an ITGCNU lesion.

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Acknowledgements

The authors would like to thank the many collaborators involved in our own studies refered to in this review, as well as the urologists and pathologists who actively participate by providing tissues. The Dutch Cancer Society is acknowledged for its financial support.

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Authors and Affiliations

  1. Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Dr. Molewaterplein 50, Rotterdam, 3015 GE, The Netherlands

    J. Wolter Oosterhuis & Leendert H. J. Looijenga

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  1. J. Wolter Oosterhuis
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  2. Leendert H. J. Looijenga
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Correspondence to J. Wolter Oosterhuis.

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DATABASES

Entrez Gene

BAX

BCAT1

CCND2

EKI1

Fhit

GRB7

JUP

KIT

KRAS

LDHB

NANOG

OCT3/4

p21

p27

p53

PLAP

Pten

RB

SRPK1

Steel

STELLAR

Ter

TSPY

VASA

XIST

XPA

FURTHER INFORMATION

Genomic imprinting

Mouse imprinting

Talk on genomic imprinting by David Haig

Glossary

RETROPERITONEAL

Located at the back of the abdomen, behind the lining known as the peritoneum that covers organs such as the stomach, liver, and parts of the large and small intestine. Organs such as the pancreas and kidneys are retroperitoneal.

MEDIASTINAL

Anatomical space of the thorax. Organs such as the thymus and heart are found within the mediastinum.

YOLK-SAC TUMOUR

Subtype of the non-seminomatous germ-cell tumour that histologically resembles the yolk sac. It can appear as a pure tumour or as a part of a mixed non-seminomatous germ-cell tumour.

EPIBLAST

Columnar epithelium that lines the floor of the amniotic sac. This layer generates endoderm and mesoderm by migration of cells through the primitive streak. The remaining cells form ectoderm.

GENITAL RIDGES

A paired fold in the dorsal lining of the abdominal cavity of the embryo in which the gonads develop.

HYDATIDIFORM MOLE

Benign gestational neoplasm, grossly presenting as a bunch of grapes.

PARTHENOGENETIC OOCYTES

Oocytes that progress beyond meiosis I without being fertilized.

CRYPTORCHIDISM

The failure of the testes to descend into the scrotum.

GONADAL DYSGENESIS

Defective development of the gonads such as that seen in Turner's syndrome, where patients have only one complete X chromosome.

EMBRYOID BODIES

Cellular structures that arise when embryonic stem cells are cultured in vitro; they contain tissues from all three germ layers — endoderm, mesoderm and ectoderm.

ISOCHROMOSOME

An abnormal chromosome having a median centromere and two identical arms.

DESMOSOME

An adhesive junction that anchors intermediate filaments between adjoining cells.

INTERMEDIATE JUNCTIONS

Intermediate junctions are made of thickened cell membranes; the extra thickness is caused by polysaccharide, mostly hyaluronic acid, gluing the membranes together.

MICROLITHIASIS

The formation of minute deposits of mainly inorganic material in tissues; for example, in the seminiferous tubules of the testis.

GYNOGENOTES

Animals with maternal chromosomes only that are artificially created using nuclear transfer experiments. Experimental gynogenotes support outgrowth of the somatic tissues of the embryo proper.

ANDROGENOTES

Animals with paternal chromosomes only that are artificially created using nuclear transfer experiments. Androgenotes support the development of the trophoblast.

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Oosterhuis, J., Looijenga, L. Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer 5, 210–222 (2005). https://doi.org/10.1038/nrc1568

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