Expression of interleukin-13 receptor α2 in glioblastoma multiforme:: Implications for targeted therapies

Glioblastoma multiforme is the most common primary malignant brain tumor and despite treatment with surgery, radiation, and chemotherapy, the median survival of patients with glioblastoma multiforme is similar to I year. Glioblastoma multiforme explants and cell lines have been reported to overexpress the interleukin-13 receptor alpha 2 subunit (ILI3R alpha 2) relative to nonneoplastic brain. Based on this finding, a recombinant cytotoxin composed of IL13 ligand and a truncated form of Pseudomonas aeraginosa exotoxin A (IL-PE38QQR) was developed for the targeted treatment of glioblastoma multiforme tumors. In a recently completed phase III clinical trial, however, IL13-PE38QQR was found to be no more effective than an existing therapy in prolonging survival. To determine possible explanations for this result, we analyzed the relative expression levels of IL13R alpha 2 in glioblastoma multiforme and nonneoplastic brain specimens using publicly available oligonucleotide microarray databases, quantitative real-time reverse transcription PCR, and inummohistochemical staining. Increased expression of the IL13R alpha 2 gene relative to nonneoplastic brain was observed in 36 of 81 (44%) and 8 of 17 (47%) tumor specimens by microarray and quantitative real-time reverse transcription PCR analyses, respectively. Inummohistochemical staining of tumor specimens showed highly variable expression of IL13R alpha 2 protein both within and across specimens. These data indicate that prescreening of subjects may he of benefit in future trials of IL13R alpha 2 targeting therapies.