Identification of interleukin-13 receptor α2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma

Bharat H. Joshi, Rada A. Puri, Pamela Leland, Frederick Varricchio, Ghanshyam Gupta, Mehmet Kocak, Richard J. Gilbertson, Raj K. Puri

Research output: Contribution to journalArticle

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Abstract

Human malignant glioma cell lines and adult brain tumors overexpress high levels of interleukin-13 receptor α2 chain (IL-13Rα2). Because the IL-13Rα2 chain is an important target for cancer therapy and prognosis for patients with brainstem glioma (BSG) remains dismal, we investigated the expression of this receptor in specimens of diffusely infiltrative pediatric BSG relative to normal brain tissue. Twenty-eight BSG specimens and 15 normal brain specimens were investigated for IL-13Rα2 protein expression by immunohistochemical analysis (IHC) using two different antibodies in two different laboratories. Highly sensitive Q-dot-based IHC and in situ hybridization (ISH) assays were also developed to identify IL-13Rα2 protein and RNA in these specimens. The results were evaluated independently in two laboratories in a blinded fashion. By Q-dot IHC or a standard IHC assay, 17 of 28 (61%) tumor specimens showed modest to strong staining for IL-13Rα2, while 15 normal brain tissue samples showed weak expression for IL-13Rα2 protein. Significant interrater agreement between the two laboratories was seen in the assessment of IL-13Rα2 intensity. High-level IL-13Rα2 RNA expression was detected in tumor samples by Q-dot ISH, but only weak RNA expression was observed in normal brain. Significant agreement between ISH and IHC assays was observed (simple kappa [k] estimate = 0.358, weighted k = 0.89, p = 0.001). IL-13Rα2 protein and mRNA are expressed to significantly higher levels in BSG than in normal brain tissue. Both IHC and ISH represent robust methods to detect expression of the IL-13Rα2 receptor in BSG that could represent an important new drug target for treatment of this disease.

Original languageEnglish (US)
Pages (from-to)265-274
Number of pages10
JournalNeuro-oncology
Volume10
Issue number3
DOIs
StatePublished - Jun 1 2008

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Interleukin-13 Receptors
Glioma
Brain Stem
Pediatrics
In Situ Hybridization
Brain
RNA
Proteins
Neoplasms
Brain Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Identification of interleukin-13 receptor α2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma. / Joshi, Bharat H.; Puri, Rada A.; Leland, Pamela; Varricchio, Frederick; Gupta, Ghanshyam; Kocak, Mehmet; Gilbertson, Richard J.; Puri, Raj K.

In: Neuro-oncology, Vol. 10, No. 3, 01.06.2008, p. 265-274.

Research output: Contribution to journalArticle

Joshi, Bharat H. ; Puri, Rada A. ; Leland, Pamela ; Varricchio, Frederick ; Gupta, Ghanshyam ; Kocak, Mehmet ; Gilbertson, Richard J. ; Puri, Raj K. / Identification of interleukin-13 receptor α2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma. In: Neuro-oncology. 2008 ; Vol. 10, No. 3. pp. 265-274.
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