This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heimberger, A. B. Articles by Bar-Eli, M. Search for Related Content PubMed PubMed Citation Articles by Heimberger, A. B. Articles by Bar-Eli, M.

Loss of the AP-2 Transcription Factor Is Associated with the Grade of Human Gliomas

Departments of ¹ Neurosurgery, ² Cancer Biology, and ³ Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas and ⁴ Hilton Head Regional Medical Center, Hilton Head, South Carolina

Requests for reprints: Amy B. Heimberger, Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Unit 442, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-2400; Fax: 713-794-4950; E-mail: aheimber{at}mdanderson.org.

Purpose: The activator protein (AP)-2 transcription factor plays a crucial role in the progression of several human tumors, including malignant melanoma, prostate, and breast cancer. Loss of AP-2 results in deregulation of several genes with AP-2 binding motifs such as E-cadherin, p21^WAF1, MMP-2, MCAM/MUC18, VEGF, and c-KIT. The purpose of our study was to determine AP-2 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-2 expression was determined by immunohistochemistry.

Results: AP-2 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-2. The loss of AP-2 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-2 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-2 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-2 would be the most common (96.2%) molecular marker as an astrocytic tumor evolves from grade 2 to 3.

Key Words: astrocytoma • oligodendroglioma • glioblastoma multiforme • activator protein

This article has been cited by other articles:

				A. B. Heimberger, M. Abou-Ghazal, C. Reina-Ortiz, D. S. Yang, W. Sun, W. Qiao, N. Hiraoka, and G. N. Fuller Incidence and Prognostic Impact of FoxP3+ Regulatory T Cells in Human Gliomas Clin. Cancer Res., August 15, 2008; 14(16): 5166 - 5172. [Abstract] [Full Text] [PDF]

				H.-J. Choi, T.-W. Chung, S.-J. Kim, S.-Y. Cho, Y.-S. Lee, Y.-C. Lee, J.-H. Ko, and C.-H. Kim The AP-2{alpha} transcription factor is required for the ganglioside GM3-stimulated transcriptional regulation of a PTEN gene Glycobiology, May 1, 2008; 18(5): 395 - 407. [Abstract] [Full Text] [PDF]

				J. A. Barnett, D. L. Urbauer, G. I. Murray, G. N. Fuller, and A. B. Heimberger Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target Clin. Cancer Res., June 15, 2007; 13(12): 3559 - 3567. [Abstract] [Full Text] [PDF]

				G. D. Maurer, J. H. Leupold, D. M. Schewe, T. Biller, R. E. Kates, H.-M. Hornung, U. Lau-Werner, S. Post, and H. Allgayer Analysis of Specific Transcriptional Regulators as Early Predictors of Independent Prognostic Relevance in Resected Colorectal Cancer Clin. Cancer Res., February 15, 2007; 13(4): 1123 - 1132. [Abstract] [Full Text] [PDF]

				A. Lopez-Soto, A. Quinones-Lombrana, R. Lopez-Arbesu, C. Lopez-Larrea, and S. Gonzalez Transcriptional Regulation of ULBP1, a Human Ligand of the NKG2D Receptor J. Biol. Chem., October 13, 2006; 281(41): 30419 - 30430. [Abstract] [Full Text] [PDF]

				N. Wajapeyee, R. Britto, H. M. Ravishankar, and K. Somasundaram Apoptosis Induction by Activator Protein 2{alpha} Involves Transcriptional Repression of Bcl-2 J. Biol. Chem., June 16, 2006; 281(24): 16207 - 16219. [Abstract] [Full Text] [PDF]

				N. Wajapeyee, C. G. Raut, and K. Somasundaram Activator Protein 2{alpha} Status Determines the Chemosensitivity of Cancer Cells: Implications in Cancer Chemotherapy Cancer Res., October 1, 2005; 65(19): 8628 - 8634. [Abstract] [Full Text] [PDF]