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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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Kaplan-meier estimates of overall survival according to level of nestin expression. Nestin expression, stratified as low, intermediate, or high expression, appears to have no statistically significant relationship with overall survival.
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Figure 2: Kaplan-meier estimates of overall survival according to level of nestin expression. Nestin expression, stratified as low, intermediate, or high expression, appears to have no statistically significant relationship with overall survival.

Mentions: The original RTOG TMA consisted of 156 GBM patients, of which, 153 were evaluable. Of these, the total number of patients that comprised the low, intermediate, and high expression groups were 17, 70, and 66 patients, respectively. The pretreatment characteristics of patients in these three groups appear in Table 3. There were no statistically significant differences seen between the three groups, although there is a trend towards more of the patients with intermediate nestin expression level in RPA III (p = 0.08). When the three groups were compared with regards to OS and PFS based on the log-rank test, no differences were seen at the significance level of 0.05 (Table 4 and 5). Corresponding Kaplan-Meier survival curves are shown in Figures 2, 3. The 12-month survival rates for the patients with low, intermediate, and high nestin expression were 59%, 49%, and 48% respectively. The 12-month PFS rates for the patients with low, intermediate, and high nestin expression were 29%, 27%, and 23% respectively.


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)

Kaplan-meier estimates of overall survival according to level of nestin expression. Nestin expression, stratified as low, intermediate, or high expression, appears to have no statistically significant relationship with overall survival.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Kaplan-meier estimates of overall survival according to level of nestin expression. Nestin expression, stratified as low, intermediate, or high expression, appears to have no statistically significant relationship with overall survival.
Mentions: The original RTOG TMA consisted of 156 GBM patients, of which, 153 were evaluable. Of these, the total number of patients that comprised the low, intermediate, and high expression groups were 17, 70, and 66 patients, respectively. The pretreatment characteristics of patients in these three groups appear in Table 3. There were no statistically significant differences seen between the three groups, although there is a trend towards more of the patients with intermediate nestin expression level in RPA III (p = 0.08). When the three groups were compared with regards to OS and PFS based on the log-rank test, no differences were seen at the significance level of 0.05 (Table 4 and 5). Corresponding Kaplan-Meier survival curves are shown in Figures 2, 3. The 12-month survival rates for the patients with low, intermediate, and high nestin expression were 59%, 49%, and 48% respectively. The 12-month PFS rates for the patients with low, intermediate, and high nestin expression were 29%, 27%, and 23% respectively.

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