Activation of Wnt/β-catenin signaling in distinct histologic subtypes of human germ cell tumors

Michael K. Fritsch, Dominik T. Schneider, Amy E. Schuster, Fern E. Murdoch, Elizabeth J. Perlman

Research output: Contribution to journalArticle

Abstract

The molecular signaling pathways mediating human germ cell tumor (GCT) formation and progression are poorly understood despite a large number of studies detailing recurrent cytogenetic abnormalities. Germ cell tumors consist of multiple histologic subtypes and can also be divided into infantile/childhood or adolescent/adult tumors as well as gonadal or nongonadal sites of origin. All of these parameters are important in defining clinical outcome and in understanding the pathogenesis of these tumors. We utilized complementary DNA (cDNA) microarray analysis to identify differences in signal transduction pathways between 2 histologic subtypes of malignant ovarian GCTs (dysgerminomas versus ovarian endodermal sinus tumors). Hierarchical cluster analysis using only the genes involved in Wnt/β-catenin signaling was able to distinguish these 2 tumor subtypes from each other. Wnt13 and β-catenin showed significant differential expression patterns between the 2 tumor subtypes, and the results were confirmed by semiquantitative reverse transcriptase-polymerase chain reaction. Additional GCTs were studied for the expression of other members of Wnt/β-catenin signaling, including Wnt13, frizzled, disheveled, low-density lipoprotein receptor-related protein 6, and β-catenin. Differential expression levels were identified for several histologic subtypes of human GCTs. Finally, we prepared tissue microarrays containing GCTs from 83 different patients and demonstrated high levels of β-catenin protein expression in 100% and nuclear accumulation in approximately 50% to 70% of all endodermal sinus tumors and immature teratomas (ITs). This pattern was independent of the patient's age. No nuclear accumulation of β-catenin was observed in germinomas, embryonal carcinomas, or choriocarcinomas. These results indicate that activation of Wnt/β-catenin signaling plays an important role in the pathogenesis of 2 histologic subtypes of human GCTs.

Original languageEnglish (US)
Pages (from-to)115-131
Number of pages17
JournalPediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
Volume9
Issue number2
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Catenins
Germ Cell and Embryonal Neoplasms
Endodermal Sinus Tumor
Low Density Lipoprotein Receptor-Related Protein-6
Neoplasms
Dysgerminoma
Germinoma
Embryonal Carcinoma
Choriocarcinoma
Teratoma
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Chromosome Aberrations
Cluster Analysis
Signal Transduction
Complementary DNA
Genes

Keywords

  • Children
  • Expression arrays
  • Gene expression profiles
  • Germ cell tumor
  • Germinoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Cite this

Activation of Wnt/β-catenin signaling in distinct histologic subtypes of human germ cell tumors. / Fritsch, Michael K.; Schneider, Dominik T.; Schuster, Amy E.; Murdoch, Fern E.; Perlman, Elizabeth J.

In: Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, Vol. 9, No. 2, 03.2006, p. 115-131.

Research output: Contribution to journalArticle

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