Abstract
Epithelial differentiation in glioblastomas (GBM) may be associated with circumscribed growth and focal keratin expression resembling carcinoma metastasis. Therefore these rare lesions can pose a diagnostic problem suggesting coincidental occurrence of two separate neoplasms. However molecular analysis should succeed in establishing a common origin of seemingly unrelated tumor samples. Five GBMs exhibiting epithelial differentiation were microdissected and analyzed for mutations in the TP53 gene. SSCP analysis of exons 5–8 was followed by direct sequencing of aberrantly migrating fragments. TP53 mutations were identified in tumors from two of five patients. A G → T transversion in codon 176 was detected in a tumor, initially diagnosed as metastases of unknown origin, however, a later autopsy revealed GBM. In this lesion, the mutation was observed in both, areas of astrocytic differentiation and areas of epithelial differentiation. One tumor diagnosed as GBM with epithelial differentiation carried C→T transition in codon 211 in both, areas of astrocytic and epithelial differentiation. Thus, molecular analysis proved clonality in two GBMs with epithelial differentiation, thereby excluding a collision tumor. The present data support the concept of clonal origin of these morphologically heterogeneous lesions.
Full Text
The Full Text of this article is available as a PDF (235.2 KB).
References
- 1. Bender B, Wiestler OD, von Deimling A (1994) A device for processing large acrylamide gels. Biotechniques 16: 204–206. [PubMed] [Google Scholar]
- 2. Bögler O, Huang SH‐J, Kleihues P, Cavenee WK (1995) The p53 gene and its role in human brain tumors. Glia 15: 308–327. [DOI] [PubMed] [Google Scholar]
- 3. Chen PC, Chen CK, Nicastri AD, Wait RB (1994) Myoepithelial carcinoma of the breast with distant metastasis and accompanied by adenomyoepitheliomas. Histopathology 24: 543–8. [DOI] [PubMed] [Google Scholar]
- 4. Chung RY, Whaley J, Kley N, Anderson K, Louis D, Menon A, Hettlich C, Freiman R, Hedley‐Whyte ET, Martuza R, Jenkins R, Yandell D, Seizinger BR (1991) TP53 mutation and 17p deletion in human astrocytomas. Genes Chromosom Cancer 3: 323–331. [DOI] [PubMed] [Google Scholar]
- 5. Doglioni C, Barbareschi M, Balercia G, Bontempini L, Iuz‐zolino P (1993) Atypical lung carcinoid with GFAP immunoreactive cells. Pathol Res Pract 189: 83–9; discussion 90–2. [DOI] [PubMed] [Google Scholar]
- 6. Frankel RH, Bayona W, Koslow M, Newcomb EW (1992) p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res 52: 1427–1433. [PubMed] [Google Scholar]
- 7. Fults D, Brockmeyer D, Tullous MW, Pedone CA, Cawthon RM (1992) p53 mutation and loss of heterozygosity on chromosome 17 and 10 during human astrocytoma progression. Cancer Res 52: 674–679. [PubMed] [Google Scholar]
- 8. Galloway PG, Roessmann U (1986) Anaplastic astrocytoma mimicking metastatic carcinoma. Am J Surg Pathol 10: 728–32. [DOI] [PubMed] [Google Scholar]
- 9. Hayashi Y, Ueki K, Waha A, Wiestler OD, Louis DN, von Deimling A (1997) Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme. Brain Pathol 7: 871–875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Ichimura K, Bolin MB, Goike HM, Schmidt EE, Moshref A, Collins VP (2000) Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1‐S transition control gene abnormalities. Cancer Res 60: 417–24. [PubMed] [Google Scholar]
- 11. Kato K, Watanabe M (1999) Glioblastoma multiforme with epithelial appearance: a case report. Brain Tumor Pathol 16: 45–8. [DOI] [PubMed] [Google Scholar]
- 12. Kattar MM, Kupsky WJ, Shimoyama RK, Vo TD, Olson MW, Bargar GR, Sarkar FH (1997) Clonal analysis of gliomas. Hum Pathol 28: 1166–79. [DOI] [PubMed] [Google Scholar]
- 13. Kepes JJ, Fulling KH, Garcia JH (1982) The clinical significance of “adenoid” formations of neoplastic astrocytes, imitating metastatic carcinoma, in gliosarcomas. A review of five cases. Clin Neuropathol 1: 139–50. [PubMed] [Google Scholar]
- 14. Kleihues P. W.K. C (2000) Pathology and genetics of tumours of the nervous system, 1, IARC Press: Lyon . [Google Scholar]
- 15. Louis DN, von Deimling A, Chung RY, Rubio MP, Whaley JH, Eibl R, Ohgaki H, Wiestler OD, Thor AD, Seizinger BR (1993) Comparative study of p53 gene and protein alterations in human astrocytoma. J Neuropath Exp Neurol 52: 31–38. [DOI] [PubMed] [Google Scholar]
- 16. Meyer‐Puttlitz B, Hayashi Y, Waha A, Rollbrocker B, Boström J, Wiestler OD, Louis DN, Reifenberger G, von Deimling A (1997) Molecular genetic analysis of giant cell glioblastomas. Am J Pathol 151: 853–857. [PMC free article] [PubMed] [Google Scholar]
- 17. Moork SJ, Rubinstein LJ, Kepes JJ, Perentes E, Uphoff DF (1988) Patterns of epithelial metaplasia in malignant gliomas. II. Squamous differentiation of epithelial‐like formations in gliosarcomas and glioblastomas. J Neuropathol Exp Neurol 47: 101–18. [DOI] [PubMed] [Google Scholar]
- 18. Ohgaki H, Eibl RH, Schwab M, Reichel MB, Mariani L, Gehring M, Petersen I, Höll T, Wiestler OD, Kleihues P (1993) Mutations in the p53 tumor suppressor gene in neoplasms of the human nervous system. Molecular Carcinogenesis 8: 74–80. [DOI] [PubMed] [Google Scholar]
- 19. Peraud A, Watanabe K, Plate KH, Yonekawa Y, Kleihues P, Ohgaki H (1997) p53 mutations versus EGF receptor expression in giant cell glioblastomas. J Neuropath Exp Neurol 56: 1236–1241. [DOI] [PubMed] [Google Scholar]
- 20. Rosenblum MK, Erlandson RA, Budzilovich GN (1991) The lipidrich epithelioid glioblastoma. Am J Surg Pathol 15: 925–34. [DOI] [PubMed] [Google Scholar]
- 21. Von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, Kleihues P, Chung RY, Wiestler OD, Seizinger BR (1992) p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52: 2987–2990. [PubMed] [Google Scholar]
- 22. Von Deimling A, Fimmers R, Schmidt MC, Bender B, Fassbender F, Nagel J, Jahnke R, Kaskel P, Duerr E‐M, Koopmann J, Maintz D, Schild S, Vogel Y, Wick W, Platten M, Müller D, Przkora R, Waha A, Rollbrocker B, Wellenreuther R, Meyer‐Puttlitz B, Schmidt O, Mollenhauer J, Poustka A, Stangl AP, Lenartz D, von Ammon K, Henson JW, Schramm J, Louis DN, Wiestler OD (2000) Comprehensive allelotype and genetic analysis of 466 human nervous system tumors. J Neuropathol Exp Neurol In Press. [DOI] [PubMed] [Google Scholar]
- 23. Von Deimling A, von Ammon K, Schoenfeld D, Wiestler OD, Seizinger BR, Louis DN (1993) Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3: 19–26. [DOI] [PubMed] [Google Scholar]
- 24. Watanabe K, Tachibana O, Sato K, Yonekawa Y, Kleihues P, Ohgaki H (1996) Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6: 217–223. [DOI] [PubMed] [Google Scholar]