Advertisement

Journal of Neuro-Oncology

, Volume 74, Issue 2, pp 151–154 | Cite as

Alterations in p53, p21, and MIB-1 Labeling Index in Primary Human Astrocytomas Following Radiation Therapy

  • John W. Henson
  • Wendy Hobbs
  • Arnab Chakravarti
  • David N. Louis
Laboratory Investigation

Summary

Little is known about the cellular and genetic changes that occur in human astrocytomas following radiation therapy (RT). Experimental studies would suggest that early effects include induction of p53 and p21 expression, cell cycle arrest, and selection of tumor cells with molecular changes that correlate with radiation resistance. Unfortunately, tissue sampling of primary human astrocytomas closely following radiation therapy is uncommon, hindering comparative assessment of primary human tumors. Through local databases, we were able to collect eight cases in which tissue was resected within 8 weeks of RT because of bulky residual disease: two patients with grade II diffuse astrocytomas (LGA) and 6 patients with high-grade astrocytomas (HGA; 1 anaplastic astrocytoma, 5 glioblastomas). Routine histopathologic sections, MIB-1 labeling index (LI), p53 and p21 expression, and EGFR expression were compared between the pre- and post-RT samples. Only one tumor (52d post-RT) showed prominent radiation-induced histopathologic changes. p53 expression was detected in two tumors pre-RT and in six tumors post-RT. In the four tumors in which p53 expression was induced, the post-RT LI was lower in each case, and p21 expression had increased in 3/4 of these cases. No change in LI was detected in tumors in which p53 expression was unchanged. EGFR expression was not altered following RT. The results of this unique series document that some primary human astrocytomas increase expression of p53 and p21 and decrease proliferation in response to RT. However, the small size of the series argues for further studies of radiation induced molecular changes in primary human astrocytoma tissue.

Keywords

EGFR glioblastoma glioma p21 p53 radiation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Salazar, C, Rubin, P, Feldstein, M. 1979High dose radiation therapy in the treatment of malignant gliomas: final reportInt J Rad Oncol Biol Phys517331740Google Scholar
  2. 2.
    Barker, FG, Prados, MD, Chang, SM, Gutin, PH, Lamborn, KR, Larson, DA, Malec, MK, McDermott, MW, Sneed, PK, Wara, WM, Wilson, CB. 1996Radiation response and survival time in patients with glioblastoma multiformeJ Neurosurg84442448PubMedGoogle Scholar
  3. 3.
    Barker, FG, Simmons, ML, Chang, SM, Prados, MD, Larson, DA, Sneed, PK, Wara, WM, Berger, MS, Chen, P, Israel, MA, Aldape, KD. 2001EGFR overexpression and radiation response in glioblastoma multiformeInt J Rad Oncol Biol Phys51410418CrossRefGoogle Scholar
  4. 4.
    Lakin, ND, Jackson, SP. 1999Regulation of p53 in response to DNA damageOncogene1876447655CrossRefPubMedGoogle Scholar
  5. 5.
    Tada, M, Matsumoto, R, Onimaru, RD, Shirato, H, Sawamura, Y, Shinohe, Y. 1998Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutationsCancer Res5817931797PubMedGoogle Scholar
  6. 6.
    Nozaki, M, Tada, M, Kobayashi, H, Zhang, C, Sawamura, Y, Abe, H, Ishii, N, Meir, EG. 1999Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progressionNeuro Oncol1124137CrossRefPubMedGoogle Scholar
  7. 7.
    Barker, FG, Chang, SM, Larson, DA, Sneed, PK, Wara, WM, Wilson, CB, Berger, MS, Prados, MD, Aldape, KD. 2002p21 immunoreactivity and imaging-assessed radiosensitivity in glioblastoma multiformeProc AACR43624Google Scholar
  8. 8.
    Chakravarti, A, Chakladar, A, Delaney, MA, Latham, DE, Loeffler, JS. 2002The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a ras-dependent mannerCancer Res6243074315PubMedGoogle Scholar
  9. 9.
    Russell, DS, Rubinstein, LJ. 1989Pathology of Tumors of the Nervous System5Williams and WilkinsBaltimoreGoogle Scholar
  10. 10.
    Alderson, LM, Castleberg, RL, Harsh, GH, Louis, DN, Henson, JW. 1995Human gliomas with wild-type p53 express bcl-2Cancer Res559991001PubMedGoogle Scholar
  11. 11.
    Tortosa, A, Ino, Y, Odell, N, Swilley, W, Louis, DN, Henson, JW. 2000Molecular genetics of radiographically-defined de novo GBMNeuropathol Appl Neurobiol26544552CrossRefPubMedGoogle Scholar
  12. 12.
    Louis, DN, Deimling, A, Chung, RY, Rubio, MP, Whaley, JM, Eibl, RH, Ohgaki, H, Weistler, OD. 1993comparative study of p53 gene and protein alterations in human astrocytic tumorsJ Neuropathol Exp Neurol523138PubMedGoogle Scholar
  13. 13.
    Rojas, M, Yao, S, Lin, YZ. 1996Controlling epidermal growth factor (EGF)-stimulated Ras activation in intact cells by a cell-permeable peptide mimicking phosphorylated EGF receptorJ Biol Chem2712745627461CrossRefPubMedGoogle Scholar
  14. 14.
    Hall, PA, McKee, PH, Menage, H, Dover, R, Lane, DP. 1993High levels of p53 protein in UV-irradited normal human skinOncogene8203207PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • John W. Henson
    • 1
    • 2
    • 5
  • Wendy Hobbs
    • 1
  • Arnab Chakravarti
    • 3
    • 5
  • David N. Louis
    • 1
    • 4
    • 5
  1. 1.Molecular Neuro-oncology LaboratoryMassachusetts General HospitalCharlestownUSA
  2. 2.Brain Tumor CenterUSA
  3. 3.Radiation Oncology ServiceUSA
  4. 4.Department of Pathology and Cancer CenterMassachusetts General HospitalBostonUSA
  5. 5.Harvard Medical SchoolBostonUSA

Personalised recommendations