title: Regional heterogeneity of EGFR gene amplification and nuclear morphology in glioblastomas. An investigation using laser microdissection and pressure catapulting.
abstract: OBJECTIVE
  To study the regional heterogeneity of epidermal growth factor receptor (EGFR) gene amplification (EGFR-GA) in glioblastomas, considering the relationship between this mutation and morphology of tumor cell nuclei.
  
  
  METHODS
  Tissue samples gained by laser microdissection and pressure catapulting were used for the performance of differential polymerase chain reaction in 32 morphologically different regions from 7 glioblastomas. Semiquantitative determination of EGFR expression and image analysis of tumor cell nuclei were performed in the same regions.
  
  
  RESULTS
  Distinct regional differences concerning the degree of EGFR-GA were found in 2 tumor cases. When comparing regions with different degrees of gene amplification within these cases, morphologic differences in tumor cell nuclei were observed. The other tumor cases also showed distinct intratumoral heterogeneity concerning histomorphology but no regional heterogeneity in the degree of EGFR-GA. When comparing regions with a low densitometric EGFR/interferon (INF) band ratio (< 2.19, n = 18) and a high EGFR/IFN band ratio (> 4.39, n = 14), the latter type of region showed a significantly higher percentage of Ki-67--positive tumor cell nuclei and lower values for several shape variables (Fourier amplitudes), indicating a tendency toward a more regular nuclear shape in regions with distinct EGFR-GA. For the EGFR/IFN band ratio, a significant correlation was found with several morphometric variables, especially those of nuclear shape and distances between nuclei.
  
  
  CONCLUSIONS
  In glioblastomas showing regional heterogeneity in the degree of EGFR-GA, morphology of tumor cell nuclei has been shown to be different when comparing regions with different degrees of EGFR-GA. Glioblastomas may also show distinct regional heterogeneity of histomorphology without evidence of regional heterogeneity of EGFR-GA. A significant statistical association has been confirmed between the degree of EGFR-GA and quantitative morphology of tumor cell nuclei.
authors.affiliation: Departments of Neuroradiology, Hematology and Neuropathology, Edinger Institute, Clinics of Johann Wolfgang Goethe University, Frankfurt, Germany. r.nafe@em.uni-frankfurt.de
authors.forename: Reinhold
authors.initials: R
authors.lastname: Nafe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Glienke
authors.forename: Renate
authors.initials: R
authors.lastname: Burgemeister
authors.forename: Rainer
authors.initials: R
authors.lastname: Gangnus
authors.forename: Beate
authors.initials: B
authors.lastname: Haar
authors.forename: Antje
authors.initials: A
authors.lastname: Pries
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlote
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology*; D004210:Dissection; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000235:genetics; D015530:Nuclear Matrix / Q000473:pathology
chemical_list: D007372:Interferons; D066246:ErbB Receptors