Expression of EGFR variant mRNA.

<p>EGFR v1, v2, v3 and v4 mRNA levels were expressed in R.A.U.</p

Relationship between immunohistochemical EGFR detection and clinicopathological parameters.

<p>Relationship between immunohistochemical EGFR detection and clinicopathological parameters.</p

OS and PFS according to clinical, pathological and molecular parameters.

a<p>Progression free survival (PFS).</p>b<p>Overall survival (OS).</p>c<p>Median values were used as cut-off to determinate weak and strong levels for each variant or sum (Σ) of all variants.</p

Patient PFS according to clinical and biological parameters.

<p>Probability of progression free durvival (PFS) was expressed in months, according to Simpson grade (A), histological tumor grade (B), Ki67 labeling index (C), EGFRv1v2v3v4 mRNA levels (D), ECD-Ab labeling (E), and ICD-Ab labeling (F).</p

ECD-Ab and ICD-Ab targeting.

<p><i>EGRF</i> gene contains 30 exons and generates 5 different mRNAs. Variant 1 mRNA encodes the whole EGFR isoform a. Alternative splicing generates variant mRNAs 2, 3, and 4 that encode sEGFR isoforms b, c and d respectively. EGFRvIII mutant mRNA with a 801 bp (exons 2–7) deletion produces EGFR vIII that lack amino acids 2 to 273. ECD-Ab targets EGFR extracellular domain and recognizes sEGFR and vIII mutant, whereas ICD-Ab targets EGFR intracellular domain and recognizes EGFR isorform a and vIII mutant.</p

Relationship between tumor grade, demographic data, Simpson grade, absence or presence of tumor necrosis and Ki67 labeling index.

<p>Relationship between tumor grade, demographic data, Simpson grade, absence or presence of tumor necrosis and Ki67 labeling index.</p

Comparison for ECD-Ab and ICD-Ab score labeling.

a<p>ECD-Ab and ICD-Ab labeling was expressed as Hirsch score: strong (+++, score 301–400), intermediate (++, score 201–300), low (+, score 1–200), no expression (No, score 0).</p

Distribution according to histopathological type and grade.

a<p>Tumors with or without brain invasion (w. brain inv. and w/o. brain inv.) were distinguished.</p

EGFR gene amplification.

<p>Genomic DNAs from glioma with and without EGFR amplification were used as positive and negative controls respectively. Two examples of results obtained for meningioma are presented.</p

IL-22 reduces ERK1/2 phosphorylation in GBM cell lines.

<p>(A, B) The expression of P-ERK1/2 and the total amount of ERK1/2 were analyzed by western blotting in total cellular protein extracted from U87MG (A) and U118MG (B) cells treated with IL-22 for the indicated times. Thirty mg of protein lysates was analyzed for P-ERK1/2 and total ERK1/2. The density of each P-ERK1/2 band was corrected for variance in loading, using the density of the corresponding total ERK1/2. The expression level was evaluated as the ratio of phosphorylated ERK1/2 protein densities between control (0 min) and treated cells. A representative results of three independent experiments. *, <i>p</i> < 0.05; **, <i>p</i> < 0.01; ***, <i>p</i> < 0.001; when compared with control. (C, D) Effect of U0126 on proliferation of GBM cells. BrdU cell proliferation assays of U87MG (C) and U118MG (D) cells treated for 24 h in serum-free medium with vehicle (non-treated; NT) or with 0.5 and 5 μM of U0126. The data are represented as histograms of proliferating cells in relative units. Error bars indicate ± SEM. *, <i>p</i> < 0.05; **, <i>p</i> < 0.01.</p