Clonal analysis in glioblastoma with epithelial differentiation

Epithelial differentiation in glioblastomas (GBM) may be associated with ci rcumscribed growth and focal keratin expression resembling carcinoma metast asis. Therefore these rare lesions can pose a diagnostic problem suggesting coincidental occurrence of two separate neoplasms. However molecular analy sis should succeed in establishing a common origin of seemingly unrelated t umor samples. Five GBMs exhibiting epithelial differentiation were microdis sected and analyzed for mutations in the TP53 gene. SSCP analysis of exons 5-8 was followed by direct sequencing of aberrantly migrating fragments. TP 53 mutations were identified in tumors from two of five patients. A G-->T t ransversion in codon 176 was detected in a tumor, initially diagnosed as me tastases of unknown origin, however, a later autopsy revealed GEM. In this lesion, the mutation was observed in both, areas of astrocytic differentiat ion and areas of epithelial differentiation. One tumor diagnosed as GEM wit h epithelial differentiation carried C-->T transition in codon 211 in both, areas of astrocytic and epithelial differentiation. Thus, molecular analys is proved clonality in two GBMs with epithelial differentiation, thereby ex cluding a collision tumor. The present data support the concept of clonal o rigin of these morphologically heterogeneous lesions.