Expression of a gap junction protein, connexin43, in a large panel of human gliomas: new insights.
Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. So far, diagnosis and prognosis of gliomas were based on histological and genetic criteria which need being completed by a panel of molecular markers. Highly distributed in brain, gap junction proteins, connexins, could be considered as markers of glioma progression as previous studies indicated that expression of a connexin type, connexin43 (Cx43), is inversely correlated to tumor grading. However, this assumption was weakened by the low number of glioma samples used. Taking advantage of tissue microarray technique, we pursued this analysis by studying in situ expression of Cx43 on 85 samples (37 grade IV, 18 grade III, 24 grade II, and 6 grades II to III). Our analysis confirmed the global diminution of Cx43 expression in glioblastomas that was observed in previous studies. However, this analysis brought new insights such as the following ones. First, the high number of samples permitted to show that more than 60% of glioblastomas still express Cx43. Second, no gradual decrease in Cx43 expression was observed between grades II and III, but Cx43 appeared to be a marker distinguishing oligodendrocytic and astrocytic grade III tumors. Third, independently from tumor grade, a Cx43 nuclear staining was detected in areas where leukocytes are present. In conclusion, our study emphasizes the importance of in situ immunohistochemical approaches by giving more precise insights in the subcellular localization of Cx43. It also emphasizes the necessity to carry out such analysis on a wide range of samples to circumvent the high glioma heterogeneity.
Laboratoire Signalisation et Transports Ioniques Membranaires, University of Poitiers, ERL-CNRS 7368, 1 rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 09, France.
Sophie
S
Crespin
Service of Pathology, Poitiers University Hospital, Jean Bernard, 6 rue de La Milétrie, TSA 51115, 86073, Poitiers Cedex 09, France.
Gaëlle
G
Fromont
Service of Neurosurgery, Poitiers University Hospital, Jean Bernard, 6 rue de La Milétrie, TSA 51115, 86073, Poitiers Cedex 09, France.
Michel
M
Wager
Service of Pathology, Poitiers University Hospital, Jean Bernard, 6 rue de La Milétrie, TSA 51115, 86073, Poitiers Cedex 09, France.
Pierre
P
Levillain
Laboratoire Signalisation et Transports Ioniques Membranaires, University of Poitiers, ERL-CNRS 7368, 1 rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 09, France.
Laurent
L
Cronier
Laboratoire Signalisation et Transports Ioniques Membranaires, University of Poitiers, ERL-CNRS 7368, 1 rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 09, France.
Arnaud
A
Monvoisin
Laboratoire Signalisation et Transports Ioniques Membranaires, University of Poitiers, ERL-CNRS 7368, 1 rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 09, France.
Norah
N
Defamie
Laboratoire Signalisation et Transports Ioniques Membranaires, University of Poitiers, ERL-CNRS 7368, 1 rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 09, France.
Marc
M
Mesnil
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods; D055815:Young Adult
D014408:Biomarkers, Tumor; D018031:Connexin 43; C500216:GJA1 protein, human; D009363:Neoplasm Proteins
Brain cancer; Cx43; connexins; gap junctions; glioblastoma; gliomas