Expression and prognostic significance of Oct4 and Nanog in neuroblastoma

APMIS. 2014 Sep;122(9):734-41. doi: 10.1111/apm.12207. Epub 2013 Dec 10.

Abstract

Neuroblastoma is the most common extracranial solid tumor of children, accounting for an estimated 15% cancer-related deaths in this period. It has been hypothesized that drug resistance of cancer stem cells may be responsible for chemotherapy failure, sustained tumor growth, and recurrence in many solid tumors. In this study, we investigated the expression of Octamer-binding transcription factor 4 (Oct4) and Nanog, two stem cell markers, in 47 neuroblastic tumors by immunohistochemistry and correlated their expression by other prognostic factors especially with NMYC amplification using both fluorescent and chromogenic in situ hybridization methods. Twenty three cases (48.9%) showed Oct4 signals and eight cases (17%) showed Nanog expression. All Nanog positive tumors showed Oct4 expression. Seven cases (14.1%) had NMYC amplification. There was also no association between positive Oct4 and Nanog reactivity and tumor morphology, age, mitosis-karyorrhexis index, NMYC amplification, favorable or unfavorable histology, and risk groups (p > 0.05). Cancer stem cells hypothesis is a challenging issue and controversies exist about their significance. Although our study did not show strong association between prognostic factors and expression of stem cell markers, performing of further large-scale studies of various neuroblastic tumors with various stages is suggested.

Keywords: Cancer stem cell; NMYC; Nanog; Oct4; neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Child, Preschool
  • Female
  • Gene Amplification
  • Homeodomain Proteins / biosynthesis*
  • Humans
  • Infant
  • Male
  • Mitosis
  • Nanog Homeobox Protein
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / pathology*
  • Neuroblastoma / pathology*
  • Octamer Transcription Factor-3 / biosynthesis*
  • Prognosis
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc