This Article 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 Pollack, I. F. Articles by Gollin, S. M. Search for Related Content PubMed PubMed Citation Articles by Pollack, I. F. Articles by Gollin, S. M.

The Relationship between TP53 Mutations and Overexpression of p53 and Prognosis in Malignant Gliomas of Childhood¹

Departments of Neurosurgery [I. F. P., J. W. C.], Pathology [R. L. H., S. D. F., A. J. M.], Neuropathology [R. L. H., A. J. M.], and Neurology (Division of Neuro-oncology) [M. E. B.], University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; Department of Human Genetics, University of Pittsburgh Graduate School of Public Health [S. M. G.], University of Pittsburgh Cancer Institute Brain Tumor Center [I. F. P., R. L. H., A. J. M., M. E. B.]; Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213 [I. F. P., R. L. H.]; and Emory and Henry College, Emory, Virginia 24327 [R. N. S.]

The prognosis for children with high-grade gliomas remains somewhat unpredictable. Although prolonged disease control is sometimes achieved after surgery, radiotherapy, and chemotherapy, most patients exhibit rapid disease progression. Because p53-dependent apoptosis mechanisms are involved in the cytotoxic effects of irradiation and chemotherapy, we questioned whether p53 status might be associated with outcome in childhood malignant gliomas. Therefore, we examined p53 status, both immunohistochemically and by direct sequencing of exons 5–8, in a series of 29 archival pediatric malignant non-brainstem gliomas treated consecutively at our institution between 1975 and 1992. Eighteen tumors had dense p53 staining in the majority of cells, although only 11 had mutations of the p53 gene (TP53). On univariate analysis, there was a significant association between p53 overexpression and a shorter progression-free survival (PFS) and overall survival (OS; P = 0.019 and 0.013, respectively; rank sum test). In addition, there was a significant association between TP53 mutations and a poorer PFS (P = 0.04), and a strong trend toward a shorter OS among patients with TP53 mutations (P = 0.06). Median PFS and OS for patients with TP53-mutated tumors were 6 months and 16 months, respectively, and for those with p53 overexpression 5.5 months and 14 months, respectively, versus 16 months and 25 months, respectively, for those without TP53 mutations and 25 months and >4 years, respectively, for those without p53 overexpression. The percentage of patients in this series with TP53 mutations (37.9%) was substantially higher than in previous studies of childhood gliomas and comparable to the frequency of mutations noted in adult gliomas. However, both TP53 mutation and p53 overexpression were significantly less frequent in tumors from children younger than 4 than from older children (P = 0.02 and 0.01, respectively). These results indicate that p53 mutation and expression status may be associated with prognosis in childhood malignant gliomas, and thus may provide a basis for stratifying patients biologically in future malignant glioma studies.

¹ This work was supported in part by a grant from the Copeland Foundation (to I. F. P.), NIH Grant 1KO8-NS01810 (to I. F. P.), the Andrew W. Mellon Trust (to R. S.), the Burroughs Wellcome Fund (to R. S.), the Appalachian College Association (to R. S.), and an American Cancer Society Career Development Award (to M. E. B.).

² To whom requests for reprints should be addressed, at Department of Neurosurgery, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213. Phone: (412) 692-5881; Fax: (412) 692-5921; E-mail: Ian_Pollack@poplar.chp.edu.

Received 7/23/96. Accepted 12/ 3/96.

This article has been cited by other articles:

				D. Faury, A. Nantel, S. E. Dunn, M.-C. Guiot, T. Haque, P. Hauser, M. Garami, L. Bognar, Z. Hanzely, P. P. Liberski, et al. Molecular Profiling Identifies Prognostic Subgroups of Pediatric Glioblastoma and Shows Increased YB-1 Expression in Tumors J. Clin. Oncol., April 1, 2007; 25(10): 1196 - 1208. [Abstract] [Full Text] [PDF]

				M. Nakamura, K. Shimada, E. Ishida, T. Higuchi, H. Nakase, T. Sakaki, and N. Konishi Molecular pathogenesis of pediatric astrocytic tumors Neuro-oncol, April 1, 2007; 9(2): 113 - 123. [Abstract] [Full Text] [PDF]

				I. F. Pollack, J. M. Boyett, A. J. Yates, P. C. Burger, F. H. Gilles, R. L. Davis, J. L. Finlay, and for the Children's Cancer Group The influence of central review on outcome associations in childhood malignant gliomas: Results from the CCG-945 experience Neuro-oncol, July 1, 2003; 5(3): 197 - 207. [Abstract] [PDF]

				I. F. Pollack, S. D. Finkelstein, J. Woods, J. Burnham, E. J. Holmes, R. L. Hamilton, A. J. Yates, J. M. Boyett, J. L. Finlay, R. Sposto, et al. Expression of p53 and Prognosis in Children with Malignant Gliomas N. Engl. J. Med., February 7, 2002; 346(6): 420 - 427. [Abstract] [Full Text] [PDF]

				I. F. Pollack, S. D. Finkelstein, J. Burnham, E. J. Holmes, R. L. Hamilton, A. J. Yates, J. L. Finlay, and R. Sposto Age and TP53 Mutation Frequency in Childhood Malignant Gliomas: Results in a Multi-institutional Cohort Cancer Res., October 1, 2001; 61(20): 7404 - 7407. [Abstract] [Full Text] [PDF]

				I. F. Pollack, M. Erff, and A. Ashkenazi Direct Stimulation of Apoptotic Signaling by Soluble Apo2L/Tumor Necrosis Factor-related Apoptosis-inducing Ligand Leads to Selective Killing of Glioma Cells Clin. Cancer Res., May 1, 2001; 7(5): 1362 - 1369. [Abstract] [Full Text]

				Y. Ino, R. A. Betensky, M. C. Zlatescu, H. Sasaki, D. R. Macdonald, A. O. Stemmer-Rachamimov, D. A. Ramsay, J. G. Cairncross, and D. N. Louis Molecular Subtypes of Anaplastic Oligodendroglioma: Implications for Patient Management at Diagnosis Clin. Cancer Res., April 1, 2001; 7(4): 839 - 845. [Abstract] [Full Text]

				C. H. Rickert, R. Strater, P. Kaatsch, H. Wassmann, H. Jurgens, B. Dockhorn-Dworniczak, and W. Paulus Pediatric High-Grade Astrocytomas Show Chromosomal Imbalances Distinct from Adult Cases Am. J. Pathol., April 1, 2001; 158(4): 1525 - 1532. [Abstract] [Full Text] [PDF]

				A. Dam, J. M. Fock, V. M. Hayes, W. M. Molenaar, and E. van den Berg Recurrent astrocytoma in a child: A report of cytogenetics and TP53 gene mutation screening Neuro-oncol, July 1, 2000; 2(3): 184 - 189. [Abstract] [PDF]

				D. Kandioler-Eckersberger, C. Ludwig, M. Rudas, S. Kappel, E. Janschek, C. Wenzel, H. Schlagbauer-Wadl, M. Mittlböck, M. Gnant, G. Steger, et al. TP53 Mutation and p53 Overexpression for Prediction of Response to Neoadjuvant Treatment in Breast Cancer Patients Clin. Cancer Res., January 1, 2000; 6(1): 50 - 56. [Abstract] [Full Text]

				C. Raffel, L. Frederick, J. R. O'Fallon, P. Atherton-Skaff, A. Perry, R. B. Jenkins, and C. D. James Analysis of Oncogene and Tumor Suppressor Gene Alterations in Pediatric Malignant Astrocytomas Reveals Reduced Survival for Patients with PTEN Mutations Clin. Cancer Res., December 1, 1999; 5(12): 4085 - 4090. [Abstract] [Full Text] [PDF]

				S. D. Finkelstein, R. Dhir, M. Rabinovitz, M. Bischeglia, P. A. Swalsky, P. DeFlavia, J. Woods, A. Bakker, and M. Becich Cold-Temperature Plastic Resin Embedding of Liver for DNA- and RNA-Based Genotyping J. Mol. Diagn., November 1, 1999; 1(1): 17 - 22. [Abstract] [Full Text]

				S. D. Finkelstein, T. Hasegawa, T. Colby, and S. A. Yousem 11q13 Allelic Imbalance Discriminates Pulmonary Carcinoids from Tumorlets : A Microdissection-Based Genotyping Approach Useful in ClinicalPractice Am. J. Pathol., August 1, 1999; 155(2): 633 - 640. [Abstract] [Full Text] [PDF]

				M. Bredel, I. F. Pollack, R. L. Hamilton, and C. D. James Epidermal Growth Factor Receptor Expression and Gene Amplification in High-Grade Non-Brainstem Gliomas of Childhood Clin. Cancer Res., July 1, 1999; 5(7): 1786 - 1792. [Abstract] [Full Text] [PDF]

				J. A. Biegel Cytogenetics and molecular genetics of childhood brain tumors Neuro-oncol, April 1, 1999; 1(2): 139 - 151. [Abstract] [PDF]