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Radiological and pathological features associated with IDH1-R132H mutation status and early mortality in newly diagnosed anaplastic astrocytic tumours.

Wasserman JK, Nicholas G, Yaworski R, Wasserman AM, Woulfe JM, Jansen GH, Chakraborty S, Nguyen TB - PLoS ONE (2015)

Bottom Line: Patients diagnosed with anaplastic astrocytic tumours were included.Variables associated with IDH1-R132H status were identified by univariate and ROC analysis. 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation.Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.

View Article: PubMed Central - PubMed

Affiliation: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

ABSTRACT

Background: Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality.

Methods: Patients diagnosed with anaplastic astrocytic tumours were included. Magnetic resonance imaging was performed and immunohistochemistry was used to identify tumours with the IDH1-R132H mutation. Survival was assessed 12 months after diagnosis. Variables associated with IDH1-R132H status were identified by univariate and ROC analysis.

Results: 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation. No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1-R132H-positive tumours were less likely to die within 12 months of diagnosis (17% vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55% vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these variables demonstrated only moderate strength for predicting the IDH1-R132H mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An increased risk of death was associated with contrast-enhancement ≥ 5 cm3 in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm2 were associated with an increased risk of death in patients with IDH1-R132H-negative tumours.

Conclusions: IDH1-R132H-positive and -negative anaplastic tumours demonstrate unique features. Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.

No MeSH data available.


Related in: MedlinePlus

Pathological and radiological differences between IDH1-R132H positive and IDH1-R132H negative tumours.A and B: Immunohistochemical staining was used to identify IDH1-R132H positive tumours which demonstrated intense cytoplasmic staining (A) relative to the unstained tumour cells in IDH1-R132H negative tumours (B). C and D: An IDH1-R132H positive tumour (C) demonstrating a higher minimum ADC relative to an IDH1-R132H negative tumour (D). E and F: An IDH1-R132H positive tumour (E) demonstrating a greater volume of contrast-enhancing tumour relative to an IDH1-R132H negative tumour (F).
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pone.0123890.g001: Pathological and radiological differences between IDH1-R132H positive and IDH1-R132H negative tumours.A and B: Immunohistochemical staining was used to identify IDH1-R132H positive tumours which demonstrated intense cytoplasmic staining (A) relative to the unstained tumour cells in IDH1-R132H negative tumours (B). C and D: An IDH1-R132H positive tumour (C) demonstrating a higher minimum ADC relative to an IDH1-R132H negative tumour (D). E and F: An IDH1-R132H positive tumour (E) demonstrating a greater volume of contrast-enhancing tumour relative to an IDH1-R132H negative tumour (F).

Mentions: A total of 37 patients with newly diagnosed anaplastic astrocytic tumours were included in this study, including 28 AA and 9 AOA. The demographic, clinical, and molecular data for all the patients included in subsequent analyses are summarized in Table 2. Twelve patients (33%) died within 12 months of their initial diagnosis. The IDH1-R132H mutation was detected by immunohistochemistry in 18 tumours (49%) (Fig 1A and 1B). Anaplastic oligoastrocytomas accounted for 33% and 15% of the tumours in the IDH1-positive and IDH1-negative groups, respectively. All three tumours demonstrating a loss of 1p or 19q were also IDH1-R132H positive. No tumours demonstrated a combined loss of 1p/19q.


Radiological and pathological features associated with IDH1-R132H mutation status and early mortality in newly diagnosed anaplastic astrocytic tumours.

Wasserman JK, Nicholas G, Yaworski R, Wasserman AM, Woulfe JM, Jansen GH, Chakraborty S, Nguyen TB - PLoS ONE (2015)

Pathological and radiological differences between IDH1-R132H positive and IDH1-R132H negative tumours.A and B: Immunohistochemical staining was used to identify IDH1-R132H positive tumours which demonstrated intense cytoplasmic staining (A) relative to the unstained tumour cells in IDH1-R132H negative tumours (B). C and D: An IDH1-R132H positive tumour (C) demonstrating a higher minimum ADC relative to an IDH1-R132H negative tumour (D). E and F: An IDH1-R132H positive tumour (E) demonstrating a greater volume of contrast-enhancing tumour relative to an IDH1-R132H negative tumour (F).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388816&req=5

pone.0123890.g001: Pathological and radiological differences between IDH1-R132H positive and IDH1-R132H negative tumours.A and B: Immunohistochemical staining was used to identify IDH1-R132H positive tumours which demonstrated intense cytoplasmic staining (A) relative to the unstained tumour cells in IDH1-R132H negative tumours (B). C and D: An IDH1-R132H positive tumour (C) demonstrating a higher minimum ADC relative to an IDH1-R132H negative tumour (D). E and F: An IDH1-R132H positive tumour (E) demonstrating a greater volume of contrast-enhancing tumour relative to an IDH1-R132H negative tumour (F).
Mentions: A total of 37 patients with newly diagnosed anaplastic astrocytic tumours were included in this study, including 28 AA and 9 AOA. The demographic, clinical, and molecular data for all the patients included in subsequent analyses are summarized in Table 2. Twelve patients (33%) died within 12 months of their initial diagnosis. The IDH1-R132H mutation was detected by immunohistochemistry in 18 tumours (49%) (Fig 1A and 1B). Anaplastic oligoastrocytomas accounted for 33% and 15% of the tumours in the IDH1-positive and IDH1-negative groups, respectively. All three tumours demonstrating a loss of 1p or 19q were also IDH1-R132H positive. No tumours demonstrated a combined loss of 1p/19q.

Bottom Line: Patients diagnosed with anaplastic astrocytic tumours were included.Variables associated with IDH1-R132H status were identified by univariate and ROC analysis. 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation.Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.

View Article: PubMed Central - PubMed

Affiliation: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

ABSTRACT

Background: Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality.

Methods: Patients diagnosed with anaplastic astrocytic tumours were included. Magnetic resonance imaging was performed and immunohistochemistry was used to identify tumours with the IDH1-R132H mutation. Survival was assessed 12 months after diagnosis. Variables associated with IDH1-R132H status were identified by univariate and ROC analysis.

Results: 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation. No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1-R132H-positive tumours were less likely to die within 12 months of diagnosis (17% vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55% vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these variables demonstrated only moderate strength for predicting the IDH1-R132H mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An increased risk of death was associated with contrast-enhancement ≥ 5 cm3 in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm2 were associated with an increased risk of death in patients with IDH1-R132H-negative tumours.

Conclusions: IDH1-R132H-positive and -negative anaplastic tumours demonstrate unique features. Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.

No MeSH data available.


Related in: MedlinePlus