Genomic gain and over expression of CCL2 correlate with vascular invasion in stage I non-seminomatous testicular germ-cell tumours

Int J Androl. 2011 Aug;34(4 Pt 2):e114-21; discussion e121. doi: 10.1111/j.1365-2605.2011.01161.x. Epub 2011 May 25.

Abstract

Testicular germ-cell tumours (TGCT) are the most frequent solid tumour to affect young Caucasian adult males and have increased in incidence over recent decades. In clinical stage I non-seminomas, (NSGCT) histological vascular invasion (VI) is a prognostic factor for metastatic relapse. Using array comparative genomic hybridization, we have previously shown that the presence of VI is associated with gain of a region at 17q12, containing a cluster of genes encoding inflammatory cytokines. We here confirm this finding using fluorescence in situ hybridization (FISH) demonstrating gain in 12 out of 42 (29%) assessable samples. Interrogation of previously published expression microarray data suggests that of the genes contained within this region, CCL2 [monocyte chemoattractant protein 1 (MCP1)] is frequently overexpressed in TGCT. Immunohistochemistry confirms this finding in a collection of 67 clinical stage I NSGCT, demonstrating an association with the presence of VI (p=0.049) that was not seen with VEGF-A, MMP2 or MMP9, although all were frequently expressed. This work gives further insight into the mechanisms involved in invasion in this tumour type, which may ultimately have implications for the management of patients with stage I disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Chemokine CCL2 / biosynthesis*
  • Chromosomes, Human, Pair 17 / genetics
  • Genome, Human*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 9 / biosynthesis
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Germ Cell and Embryonal / blood supply*
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neovascularization, Pathologic
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Testicular Neoplasms / blood supply*
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Biomarkers, Tumor
  • CCL2 protein, human
  • Chemokine CCL2
  • Vascular Endothelial Growth Factor A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9

Supplementary concepts

  • Nonseminomatous germ cell tumor