EGFR gene amplification in glioblastomas. Is there a relationship with morphology of tumor cell nuclei and proliferative activity?
OBJECTIVE
To confirm a relationship between histomorphology of glioblastomas and amplification of the gene for the epidermal growth factor receptor (EGFR) as the most important molecular biologic alteration in these tumors.


METHODS
In paraffin sections of surgical specimens from 71 primary resected glioblastomas, tumor cell nuclei in the region with the highest proliferative activity (Ki-67 immunostaining) were investigated morphometrically. Shape variables (roundness factor, Fourier amplitudes) and nuclear area were measured. Additionally, the numerical density of Ki-67-positive tumor cell nuclei was estimated. Differential polymerase chain reaction (PCR) was performed from paraffin sections of the same tumor area. The signals for the EGFR gene and IFN gamma reference gene were quantified densitometrically.


RESULTS
Cases with distinct EGFR gene amplification (EGFR/IFN ratios > 5) revealed significantly lower mean values for several Fourier amplitudes, indicating a more regular nuclear shape when compared with cases without evidence of EGFR gene amplification (EGFR/IFN-ratios < or = 1). The Ki-67 index and nuclear area showed no significant differences between these groups. Although a large variation in nuclear morphology was observed for cases without evidence of EGFR gene amplification, discriminant analysis based on morphometric variables provided a good separation of these cases from cases with distinct EGFR gene amplification, with a high percentage of statistically correct reclassified cases.


CONCLUSIONS
Our results provide evidence of a relationship between genetic alterations and histomorphology of glioblastomas.
Nafe
R
R
Edinger Institute for Neurology and Department of Urology, Clinics of Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Glienke
W
W
Schlote
W
W
Schneider
B
B
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology*; D003720:Densitometry; D066246:ErbB Receptors / Q000235:genetics*; D005583:Fourier Analysis; D005784:Gene Amplification; D018773:Genes, erbB-1; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D019394:Ki-67 Antigen; D066246:ErbB Receptors