Prognostic and clinical implication of a disintegrin and metalloprotease 8 expression in pediatric medulloblastoma

J Neurol Sci. 2012 Dec 15;323(1-2):46-51. doi: 10.1016/j.jns.2012.07.040. Epub 2012 Sep 7.

Abstract

Aim: To investigate the expression patterns and clinical value of a disintegrin and metalloprotease 8 (ADAM8) in pediatric medulloblastoma.

Methods: We evaluated the expression of ADAM8 mRNA and protein in pediatric medulloblastoma tissues by Quantitative RT-PCR, Western blot analysis and Immunohistochemical staining, respectively. The correlation of ADAM8 immunostaining with clinical-pathological features of medulloblastoma patients and its prognostic relevance were further determined.

Results: ADAM8 mRNA and protein were both most highly expressed in medulloblastoma tissues when compared with normal cerebellum tissues (both P<0.001). According to the immunohistochemisty analysis, we found statistically significant correlations of high ADAM8 protein expression with advanced metastatic stage (P=0.01), aggressive histopathological type (P=0.006), as well as with undifferentiated tumor (P=0.02). We further determined a statistically significant association between ADAM8 protein expression and clinical outcome of medulloblastoma patients, with higher expression levels of ADAM8 associating with a worse overall survival (P=0.02).

Conclusion: Our results provide the first evidence that the up-regulation of ADAM8 in medulloblastoma tissues might be correlated with the advanced tumor progression and poor prognosis of patients with this disease. Detection of ADAM8 expression might facilitate the prognostic assessment and improve the therapeutic strategy for medulloblastoma patients.

MeSH terms

  • ADAM Proteins / analysis*
  • ADAM Proteins / biosynthesis
  • ADAM Proteins / genetics
  • Cell Differentiation
  • Cerebellar Neoplasms / enzymology*
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / surgery
  • Cerebellum / enzymology
  • Child
  • Child, Preschool
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Medulloblastoma / enzymology*
  • Medulloblastoma / mortality
  • Medulloblastoma / pathology
  • Medulloblastoma / surgery
  • Membrane Proteins / analysis*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Necrosis
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Treatment Outcome
  • Up-Regulation

Substances

  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • ADAM Proteins
  • ADAM8 protein, human