PURPOSE: The activator protein (AP)-2alpha transcription factor plays a crucial role in the progression of several human tumors, including malignant melanoma, prostate, and breast cancer. Loss of AP-2alpha results in deregulation of several genes with AP-2alpha binding motifs such as E-cadherin, p21WAF1, MMP-2, MCAM/MUC18, VEGF, and c-KIT. The purpose of our study was to determine AP-2alpha expression distribution among grades of gliomas and any possible effect on prognosis. EXPERIMENTAL DESIGN: A tissue microarray was assembled from all surgical glioma cases with available tissue samples at M.D. Anderson Cancer Center since 1986 to include 72 glioblastomas, 49 anaplastic astrocytomas, 9 low-grade astrocytoma, 37 oligodendrogliomas, 37 anaplastic oligodendrogliomas, 15 mixed oligoastrocytomas, 20 anaplastic mixed oligoastrocytomas, and 7 gliosarcomas. The microarray included normal brain tissue, and AP-2alpha expression was determined by immunohistochemistry. RESULTS: AP-2alpha expression was lost on 99% (P < 0.001) and 98% (P < 0.001) of glioblastomas and anaplastic astrocytomas, respectively, compared with grade 2 astrocytomas and normal brain, all of which (100%) maintained expression of AP-2alpha. The loss of AP-2alpha was a negative prognostic indicator within the overall category of gliomas by univariate analysis (rate ratio, 4.30; 95% confidence interval, 2.60-7.10; P < 0.001). However, there was no significant effect of loss of AP-2alpha expression on survival observed after adjustment for patient age, Karnofsky Performance Scale score, tumor grade, and extent of resection (rate ratio, 1.2; 95% confidence interval, 0.6-2.2; P = 0.6). CONCLUSIONS: AP-2alpha expression correlates inversely with glioma grade, suggesting a direct role in glioma tumorigenicity, possibly through subsequent deregulation of target genes. Of all the previously characterized markers of progression, the loss of AP-2alpha would be the most common (96.2%) molecular marker as an astrocytic tumor evolves from grade 2 to 3.
PURPOSE: The activator protein (AP)-2alpha transcription factor plays a crucial role in the progression of several humantumors, including malignant melanoma, prostate, and breast cancer. Loss of AP-2alpha results in deregulation of several genes with AP-2alpha binding motifs such as E-cadherin, p21WAF1, MMP-2, MCAM/MUC18, VEGF, and c-KIT. The purpose of our study was to determine AP-2alpha expression distribution among grades of gliomas and any possible effect on prognosis. EXPERIMENTAL DESIGN: A tissue microarray was assembled from all surgical glioma cases with available tissue samples at M.D. Anderson Cancer Center since 1986 to include 72 glioblastomas, 49 anaplastic astrocytomas, 9 low-grade astrocytoma, 37 oligodendrogliomas, 37 anaplastic oligodendrogliomas, 15 mixed oligoastrocytomas, 20 anaplastic mixed oligoastrocytomas, and 7 gliosarcomas. The microarray included normal brain tissue, and AP-2alpha expression was determined by immunohistochemistry. RESULTS:AP-2alpha expression was lost on 99% (P < 0.001) and 98% (P < 0.001) of glioblastomas and anaplastic astrocytomas, respectively, compared with grade 2 astrocytomas and normal brain, all of which (100%) maintained expression of AP-2alpha. The loss of AP-2alpha was a negative prognostic indicator within the overall category of gliomas by univariate analysis (rate ratio, 4.30; 95% confidence interval, 2.60-7.10; P < 0.001). However, there was no significant effect of loss of AP-2alpha expression on survival observed after adjustment for patient age, Karnofsky Performance Scale score, tumor grade, and extent of resection (rate ratio, 1.2; 95% confidence interval, 0.6-2.2; P = 0.6). CONCLUSIONS:AP-2alpha expression correlates inversely with glioma grade, suggesting a direct role in glioma tumorigenicity, possibly through subsequent deregulation of target genes. Of all the previously characterized markers of progression, the loss of AP-2alpha would be the most common (96.2%) molecular marker as an astrocytic tumor evolves from grade 2 to 3.
Authors: Shengwen Calvin Li; Long T Vu; Hector W Ho; Hong Zhen Yin; Vic Keschrumrus; Qiang Lu; Jun Wang; Heying Zhang; Zhiwei Ma; Alexander Stover; John H Weiss; Philip H Schwartz; William G Loudon Journal: Cancer Cell Int Date: 2012-09-20 Impact factor: 5.722
Authors: Peter B Makhov; Konstantin V Golovine; Alexander Kutikov; Daniel J Canter; Vera A Rybko; Dmitry A Roshchin; Vsevolod B Matveev; Robert G Uzzo; Vladimir M Kolenko Journal: Carcinogenesis Date: 2011-09-22 Impact factor: 4.944
Authors: Vladislava O Melnikova; Andrey S Dobroff; Maya Zigler; Gabriel J Villares; Russell R Braeuer; Hua Wang; Li Huang; Menashe Bar-Eli Journal: PLoS One Date: 2010-08-27 Impact factor: 3.240
Authors: Mohamed Abou-Ghazal; David S Yang; Wei Qiao; Chantal Reina-Ortiz; Jun Wei; Ling-Yuan Kong; Gregory N Fuller; Nobuyoshi Hiraoka; Waldemar Priebe; Raymond Sawaya; Amy B Heimberger Journal: Clin Cancer Res Date: 2008-12-15 Impact factor: 12.531