Molecular stratification of diagnostically challenging high-grade gliomas composed of small cells: the utility of fluorescence in situ hybridization.
OBJECTIVE
There is considerable morphologic overlap between various entities of high-grade gliomas, and, therefore, a further planning of their optimal treatment is a controversial issue. The aim of this study was molecular stratification of morphologically ambiguous high-grade gliomas composed from small cells. Fluorescence in situ hybridization (FISH) with commercially available probes was used for this purpose.


METHODS
We analyzed a set of 114 high-grade small-cell gliomas that were difficult to interpret diagnostically because of their distinct cytological origin. FISH assay with locus probes for EGFR, p16, PTEN, and 1p and 19q was done.


RESULTS
Morphologically uniform high-grade gliomas composed of small cells varied greatly in terms of molecular features and clinical outcome. Four clinically relevant subsets of patients whose tumors showed distinctly different molecular profiles were identified as follows: (a) 13 patients whose tumors exhibited no discernable molecular alterations (5-year survival rate, 83%); (b) 20 patients whose tumors harbored either 1p/19q codeletion or isolated deletion of 19q unaccompanied by other molecular abnormalities (5-year survival rate, 59%); (c) 35 patients whose tumors showed p16 and/or PTEN deletions unaccompanied by EGFR amplification (5-year survival rate, 8%); and (d) 46 patients whose tumors harbored EGFR amplification (5-year survival rate, 0).


CONCLUSIONS
The FISH method provides clinically useful information in the molecular analysis of morphologically ambiguous malignant small-cell gliomas that could potentially enhance the quality of patient care.
Korshunov
Andrey
A
Department of Neuropathology, NN Burdenko Neurosurgical Institute, Fadeeva str. 5, Moscow, 125047, Russia. akorshunov@nsi.ru
Sycheva
Regina
R
Golanov
Andrey
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D019942:Genes, p16 / Q000502:physiology; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human