ALK Expression Is a Novel Marker for the WNT-activated Type of Pediatric Medulloblastoma and an Indicator of Good Prognosis for Patients

Am J Surg Pathol. 2017 Jun;41(6):781-787. doi: 10.1097/PAS.0000000000000847.

Abstract

ALK gene rearrangements were identified in a variety of cancers, including neuroblastoma, where the presence of ALK expression is associated with adverse prognosis. ALK mutations have recently been found in the pediatric brain tumor medulloblastoma, and microarray data indicate that ALK is highly expressed in a subset of these tumors. Therefore, we investigated whether ALK expression correlates with transcriptional profiles and clinical features of medulloblastoma. Tumors from 116 medulloblastoma patients were studied at diagnosis for the detection of ALK expression at the RNA level by an application of NanoString technology and at the protein level by immunohistochemistry using antibody ALK clone D5F3. The results indicate that ALK expression, at both the RNA and the protein levels, is strongly associated with the WNT-activated type of tumors and therefore may serve as a useful marker for the detection of this type of medulloblastoma. Importantly, ALK protein expression alone is also an indicator of good prognosis for medulloblastoma patients.

MeSH terms

  • Adolescent
  • Anaplastic Lymphoma Kinase
  • Biomarkers, Tumor / genetics*
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / mortality
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Medulloblastoma / diagnosis
  • Medulloblastoma / genetics*
  • Medulloblastoma / mortality
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / genetics*

Substances

  • Biomarkers, Tumor
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases