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 prot...

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Veröffentlicht in:Cancer medicine (Malden, MA) MA), 2016-08, Vol.5 (8), p.1742-1752
Hauptverfasser: Crespin, Sophie, Fromont, Gaëlle, Wager, Michel, Levillain, Pierre, Cronier, Laurent, Monvoisin, Arnaud, Defamie, Norah, Mesnil, Marc
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container_issue 8
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container_title Cancer medicine (Malden, MA)
container_volume 5
creator Crespin, Sophie
Fromont, Gaëlle
Wager, Michel
Levillain, Pierre
Cronier, Laurent
Monvoisin, Arnaud
Defamie, Norah
Mesnil, Marc
description 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. Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. Highly distributed in brain, gap junction proteins, such as connexin 43, could be considered as markers of glioma progression. Taking advantage of tissue microarray technique, we analyzed in situ expression of Cx43 on 85 samples (37 grade IV, 18 grade III, 24 grade II, and 6 grades II to III). The high number of samples shows that 60% of glioblastomas still express Cx43. 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, the detection of a Cx43 nuclear staining seemed to be related to lymphocyte infiltrations. In conclusion, our study emphasizes the importan
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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. Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. Highly distributed in brain, gap junction proteins, such as connexin 43, could be considered as markers of glioma progression. Taking advantage of tissue microarray technique, we analyzed in situ expression of Cx43 on 85 samples (37 grade IV, 18 grade III, 24 grade II, and 6 grades II to III). The high number of samples shows that 60% of glioblastomas still express Cx43. 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, the detection of a Cx43 nuclear staining seemed to be related to lymphocyte infiltrations. In conclusion, our study emphasizes the importance of in situ immunohistochemical approaches by giving more precise insights in the subcellular localization of Cx43. 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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. Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. Highly distributed in brain, gap junction proteins, such as connexin 43, could be considered as markers of glioma progression. Taking advantage of tissue microarray technique, we analyzed in situ expression of Cx43 on 85 samples (37 grade IV, 18 grade III, 24 grade II, and 6 grades II to III). The high number of samples shows that 60% of glioblastomas still express Cx43. 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, the detection of a Cx43 nuclear staining seemed to be related to lymphocyte infiltrations. In conclusion, our study emphasizes the importance of in situ immunohistochemical approaches by giving more precise insights in the subcellular localization of Cx43. 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subjects Adolescent
Adult
Aged
Biomarkers, Tumor
Biomarkers, Tumor - metabolism
Blotting, Western
Blotting, Western - methods
Brain cancer
Brain Neoplasms
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain tumors
Cell Nucleus
Cell Nucleus - metabolism
Chemotaxis, Leukocyte
Clinical Cancer Research
Connexin 43
Connexin 43 - metabolism
Connexins
Cx43
Diagnosis
Female
gap junctions
Glioblastoma
Glioblastoma - metabolism
Glioblastoma - pathology
Glioma
Glioma - metabolism
Glioma - pathology
gliomas
Humans
Leukocytes
Life Sciences
Localization
Male
Middle Aged
Neoplasm Grading
Neoplasm Proteins
Neoplasm Proteins - metabolism
Original Research
Proteins
Studies
Tissue Array Analysis
Tissue Array Analysis - methods
Tumors
Young Adult
title Expression of a gap junction protein, connexin43, in a large panel of human gliomas: new insights
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