Characterization of the levels of expression of retinoic acid receptors, galectin-3, macrophage migration inhibiting factor, and p53 in 51 adamantinomatous craniopharyngiomas.
OBJECTIVE
Craniopharyngiomas are histopathologically defined as benign tumors that can behave very aggressively at the clinical level. They can originate from different types of embryonal epithelial tissue in which correct spatiotemporal regulation has been disrupted at the effector production level. The goal of this study was to determine the efficacy of using selected biological markers to distinguish between recurring and nonrecurring craniopharyngiomas.


METHODS
The authors used computer-assisted microscopy to determine quantitatively the immunohistochemical levels of expression of selected markers, including retinoic acid receptors (RARs), as response elements to retinoic acid in a series of 51 adamantinomatous craniopharyngiomas. These tumors may also originate as the result of physiological defects in the apoptosis-mediated elimination of embryological remnants of epithelial tissue. Galectin-3, p53, and the macrophage migration inhibiting factor (MIF) are known to play crucial roles in these processes. The authors quantitatively determined the levels of expression of these substances in this series of 51 craniopharyngiomas. The data show that all craniopharyngiomas were immunoreactive for RARalpha, whereas their immunoreactivity for RARbeta and RARgamma varied dramatically from one case to another. Craniopharyngiomas with low levels of RARbeta and high levels of RARgamma are more likely to recur than those with higher levels of RARbeta and lower levels of RARgamma. Rapidly recurring craniopharyngiomas also show significantly lower levels of expression of galectin-3 and MIF than nonrecurring or slowly recurring cases. Few tumors exhibited p53 immunopositivity.


CONCLUSIONS
The data indicate that even in the so-called adamantinomatous group of craniopharyngiomas, several subgroups with different clinical behavior patterns can be identified on the basis of differentiation markers relating mainly to the presence or absence of RARbeta and RARgamma.
Lefranc
Florence
F
Department of Neurosurgery, Erasmus University Hospital and Laboratory of Histopathology, Faculty of Medicine, Free University of Brussels, Belgium.
Chevalier
Catherine
C
Vinchon
Mathieu
M
Dhellemmes
Patrick
P
Schüring
Max-Peter
MP
Kaltner
Herbert
H
Brotchi
Jacques
J
Ruchoux
Marie-Magdeleine
MM
Gabius
Hans-Joachim
HJ
Salmon
Isabelle
I
Kiss
Robert
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000473:pathology* / Q000648:ultrastructure*; D003937:Diagnosis, Differential; D005260:Female; D037502:Galectin 3 / Q000032:analysis*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000648:ultrastructure*; D010911:Pituitary Neoplasms / Q000473:pathology* / Q000648:ultrastructure*; D018168:Receptors, Retinoic Acid / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D015415:Biomarkers; D037502:Galectin 3; D008263:Macrophage Migration-Inhibitory Factors; D018168:Receptors, Retinoic Acid; D016159:Tumor Suppressor Protein p53