Stem cell marker nestin and c-Jun NH2-terminal kinases in tumor and peritumor areas of glioblastoma multiforme: possible prognostic implications.
OBJECTIVE
It has been hypothesized that brain tumors are derived from stem cell or transiently dividing precursor transformation. Furthermore, c-Jun NH(2)-terminal kinases (JNKs) have been involved in gliomagenesis. This study analyzes stem cell marker nestin and JNK expression in glioblastoma multiforme (GBM) and peritumor tissue and assesses their possible prognostic implications.


METHODS
Nestin and both total JNK (tJNK) and phosphorylated JNK (pJNK) expression was investigated by immunohistochemistry in 20 GBMs. Samples were derived from tumors (first area), from tissues at a distance <1 cm (second area), and between 1 and 3.5 cm (third area) from the macroscopic tumor border. The relationships between patients' age, Karnofsky performance status, gender, protein expression, and survival were analyzed.


RESULTS
Nestin cytoplasmic immunoreactivity was observed in the majority of cells in tumor but infrequently in peritumor areas. tJNK, observed in the nucleus and cytoplasm, was widely expressed in the three areas; pJNK, mostly located in the nuclei, was found in a variable percentage of cells in the tumor and peritumor tissue. Nestin and JNK expression in peritumor areas was independent of the presence of neoplastic cells. Univariate analysis indicated that survival was longer (19 versus 12 months; P = 0.01) for patients whose pJNK/nestin and (pJNK/tJNK)/nestin ratios in the second area were > or =2.619 and > or =0.026, respectively. The same variables showed an independent prognostic value in multivariate analysis.


CONCLUSIONS
Nestin and JNK expression indicates that peritumor tissue, independently of the presence of neoplastic cells, may present signs of transformation. Moreover, pJNK/nestin and (pJNK/tJNK)/nestin ratios in that tissue seem to have some prognostic implications in GBM patients.
Mangiola
Annunziato
A
Institute of Neurosurgery, Catholic University of the Sacred Heart, Rome, Italy.
Lama
Gina
G
Giannitelli
Cecilia
C
De Bonis
Pasquale
P
Anile
Carmelo
C
Lauriola
Libero
L
La Torre
Giuseppe
G
Sabatino
Giovanni
G
Maira
Giulio
G
Jhanwar-Uniyal
Meena
M
Sica
Gigliola
G
D000328:Adult; D000368:Aged; D004789:Enzyme Activation; D005260:Female; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D064231:Nestin; D011379:Prognosis; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D015173:Supratentorial Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D048031:JNK Mitogen-Activated Protein Kinases