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The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group.

Chinnaiyan P, Wang M, Rojiani AM, Tofilon PJ, Chakravarti A, Ang KK, Zhang HZ, Hammond E, Curran W, Mehta MP - Radiat Oncol (2008)

Bottom Line: There were no statistically significant differences between pretreatment patient characteristics and nestin expression.There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06).Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. prakash.chinnaiyan@moffitt.org

ABSTRACT

Background: Nestin is an intermediate filament protein that has been implicated in early stages of neuronal lineage commitment. Based on the heterogeneous expression of nestin in GBM and its potential to serve as a marker for a dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy Oncology Group (RTOG) sought to determine the prognostic value of nestin expression in newly diagnosed GBM patients treated on prior prospective RTOG clinical trials.

Methods: Tissue microarrays were prepared from 156 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for nestin and expression was measured by computerized quantitative image analysis using the Ariol SL-50 system. The parameters measured included both staining intensity and the relative area of expression within a specimen. This resulted into 3 categories: low, intermediate, and high nestin expression, which was then correlated with clinical outcome.

Results: A total of 153 of the 156 samples were evaluable for this study. There were no statistically significant differences between pretreatment patient characteristics and nestin expression. There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06).

Conclusion: Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM. Further studies evaluating nestin expression may be more informative when studied in lower grade glioma, in the context of markers more specific to tumor stem cells, and using more recent specimens from patients treated with temozolomide in conjunction with radiation.

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Varying levels of nestin expression in GBM. Images are representative of samples categorized as low (A), intermediate (B), and high (C) nestin expression.
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Figure 1: Varying levels of nestin expression in GBM. Images are representative of samples categorized as low (A), intermediate (B), and high (C) nestin expression.

Mentions: Detailed images were processed using the TMA Multistain Imaging Module for the nestin stained brain tissue microarrays slides. The TMAs were processed using the TMA specific imaging assay, TMA Multistain. This allows the software to distinguish positive tumor areas within individual cores of the TMA slide. Both staining intensity and its relative area within a specimen were quantified. Staining intensity was acquired in a continuous gradient and divided into tertiles defined as negative (0), lightly positive (1+), moderately positive (2+) and highly positive (3+) regions. The area occupied by each of these 4 categories was determined, and divided into similar tertiles. A score of 3, 2, 1, and 0 was designated to relative areas ≥ 50%, 33–49%, 1–33%, and 0%, respectively, within the evaluated area of the specimen. This allowed the software to automatically quantitate not only the average intensity of each category, but also the relative area of these stains. The products of the scoring system described above (relative intensity × area) yielded values ranging from 0 to 9, with higher scores reflecting more quantified nestin expression. The highest score of the individual products was used for analysis. Low, intermediate, and high expression was defined as scores ranging from 0–3, 4–6, and 7–9, respectively. Representative samples for low, intermediate, and high expression are shown in Figure 1. All specimens were manually reviewed by a neuropathologist (AMR) to verify overall quality of staining of the tissue microarray and ensure appropriate evaluation of tumor tissue versus necrosis, vessels, and/or other potential aberrances in individual specimens.


The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group.

Chinnaiyan P, Wang M, Rojiani AM, Tofilon PJ, Chakravarti A, Ang KK, Zhang HZ, Hammond E, Curran W, Mehta MP - Radiat Oncol (2008)

Varying levels of nestin expression in GBM. Images are representative of samples categorized as low (A), intermediate (B), and high (C) nestin expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2563009&req=5

Figure 1: Varying levels of nestin expression in GBM. Images are representative of samples categorized as low (A), intermediate (B), and high (C) nestin expression.
Mentions: Detailed images were processed using the TMA Multistain Imaging Module for the nestin stained brain tissue microarrays slides. The TMAs were processed using the TMA specific imaging assay, TMA Multistain. This allows the software to distinguish positive tumor areas within individual cores of the TMA slide. Both staining intensity and its relative area within a specimen were quantified. Staining intensity was acquired in a continuous gradient and divided into tertiles defined as negative (0), lightly positive (1+), moderately positive (2+) and highly positive (3+) regions. The area occupied by each of these 4 categories was determined, and divided into similar tertiles. A score of 3, 2, 1, and 0 was designated to relative areas ≥ 50%, 33–49%, 1–33%, and 0%, respectively, within the evaluated area of the specimen. This allowed the software to automatically quantitate not only the average intensity of each category, but also the relative area of these stains. The products of the scoring system described above (relative intensity × area) yielded values ranging from 0 to 9, with higher scores reflecting more quantified nestin expression. The highest score of the individual products was used for analysis. Low, intermediate, and high expression was defined as scores ranging from 0–3, 4–6, and 7–9, respectively. Representative samples for low, intermediate, and high expression are shown in Figure 1. All specimens were manually reviewed by a neuropathologist (AMR) to verify overall quality of staining of the tissue microarray and ensure appropriate evaluation of tumor tissue versus necrosis, vessels, and/or other potential aberrances in individual specimens.

Bottom Line: There were no statistically significant differences between pretreatment patient characteristics and nestin expression.There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06).Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. prakash.chinnaiyan@moffitt.org

ABSTRACT

Background: Nestin is an intermediate filament protein that has been implicated in early stages of neuronal lineage commitment. Based on the heterogeneous expression of nestin in GBM and its potential to serve as a marker for a dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy Oncology Group (RTOG) sought to determine the prognostic value of nestin expression in newly diagnosed GBM patients treated on prior prospective RTOG clinical trials.

Methods: Tissue microarrays were prepared from 156 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for nestin and expression was measured by computerized quantitative image analysis using the Ariol SL-50 system. The parameters measured included both staining intensity and the relative area of expression within a specimen. This resulted into 3 categories: low, intermediate, and high nestin expression, which was then correlated with clinical outcome.

Results: A total of 153 of the 156 samples were evaluable for this study. There were no statistically significant differences between pretreatment patient characteristics and nestin expression. There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06).

Conclusion: Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM. Further studies evaluating nestin expression may be more informative when studied in lower grade glioma, in the context of markers more specific to tumor stem cells, and using more recent specimens from patients treated with temozolomide in conjunction with radiation.

Show MeSH
Related in: MedlinePlus