J Korean Med Sci.  2013 Apr;28(4):593-601. 10.3346/jkms.2013.28.4.593.

Alpha Internexin Expression Related with Molecular Characteristics in Adult Glioblastoma and Oligodendroglioma

• Suh JH
• Park CK
• Park SH

• KMID: 1786969
• DOI: http://doi.org/10.3346/jkms.2013.28.4.593

Abstract

Alpha-internexin (INA) is a proneuronal gene-encoding neurofilament interacting protein. INA is overexpressed mostly in oligodendroglial phenotype gliomas, is related to 1p/19q codeletion, and is a favorable prognostic marker. We studied INA expression in oligodendrogliomas (ODGs) and glioblastomas (GBMs) to verify its association with several molecular phenotypes, 1p/19q codeletion, and epidermal growth-factor-receptor (EGFR) amplification. A total of 230 low- and high-grade ODG and GBM cases was analyzed for INA expression by immunohistochemical staining; and 1p/19q and EGFR gene status was examined by fluorescence in-situ hybridization. INA was positive in 80.3% of ODGs and in 34.3% of GBMs. 1p/19q codeletion was detected in 77.0% of ODGs and 5.5% of GBMs. INA and 1p/19q codeletion were strongly correlated (P < 0.001). The specificity of INA expression for 1p/19q codeletion was 70.8%, while sensitivity was 100%; positive predictive value was 72.5%, and negative predictive value was 29.2% in all 228 tumors. INA expression was correlated with better progression-free survival (PFS) and overall survival (OS) (P = 0.001). In conclusion, INA expression has high specificity and sensitivity to predict 1p/19q codeletion, and it is well correlated with PFS of both ODGs and GBMs. Therefore, INA expression could be a simple, reliable, and favorable prognostic and surrogate marker for 1p/19q codeletion and long term survival.

Keyword

Glioblastoma; Oligodendroglioma; Alpha-internexin, humans; 1p/19q Codeletion; EGFR protein, Human

MeSH Terms

Adult
Brain Neoplasms/*metabolism/mortality/pathology
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 19
Female
Gene Deletion
Glioblastoma/*metabolism/mortality/pathology
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Intermediate Filament Proteins/genetics/*metabolism
Kaplan-Meier Estimate
Male
Middle Aged
Oligodendroglioma/*metabolism/mortality/pathology
Phenotype
Predictive Value of Tests
Prognosis
Receptor, Epidermal Growth Factor/genetics/metabolism
Intermediate Filament Proteins
Receptor, Epidermal Growth Factor

Figure

• 

  Fig. 1 The photograph of the 1p/19q codeletion FISH-study and EGFR FISH-study on oligodendrogliomas (A-C) and EGFR FISH-study on glioblastomas (D). (A) 1p deletion of oligodendroglioma tumor cell nuclei. (B) 19q deletion of oligodendroglioma tumor cell nuclei. (C) Markly increased number of orange signals (EGFR gene amplification) of oligodendroglioma tumor cell nuclei are observed. (D) Markly increased number of orange signals (EGFR gene amplification) of glioblastoma tumor cell nuclei are observed (magnification, × 1,000).

• 

  Fig. 2 INA immunostaining pattern in oligodendrogliomas (A-C) and glioblastomas (D-F). (A, D) negative, (B, E) weak positive (positive in < 10% of tumor cells), (C, F) strong positive (positive in ≥ 10% of tumor cells) (magnification, × 400).

• 

  Fig. 3 Correlation with alpha-internexin (INA) and 1p/19q codeletion in oligodendrogliomas. INA immunostaining result is well correlated with 1p/19q codeletion in oligodendroglioma group.

• 

  Fig. 4 Correlation with INA and 1p/19q codeletion in glioblastomas. INA immunostaining result is well correlated with 1p/19q codeletion in glioblastoma group.

• 

  Fig. 5 Kaplan-Meier survival curves of 230 tumor patients in relation with INA expression. (A) Overall survival (OS) in 230 tumor patients in relation with INA expression. (B) Progression free survival (PFS) in 230 tumor patients in relation with INA expression.

• 

  Fig. 6 Kaplan-Meier survival curves of glioblastoma patients in relation with INA expression. (A) Overall survival in glioblastomas related with INA expression. (B) Progression-free survival in glioblastomas related with INA expression.

• 

  Fig. 7 Kaplan-Meier survival curves of oligodendroglioma patients in relation with INA expression. (A) Overall survival in oligodendroglioma s related with INA expression. (B) Progression-free survival in oligodendrogliomas related with INA expression.

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