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Expression of EGFR in Paired New and Recurrent Glioblastomas  

Cioca, Andreea (Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy)
Olteanu, Emilian Gheorghe (Department of Pathology, County Emergency Clinical Hospital)
Gisca, Monica Daniela (Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy)
Morosanu, Cezar Octavian (Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy)
Marin, Irina (Department of Pathology, Sheba Medical Center, Tel-Hashomer)
Florian, Ioan Stefan (Department of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.9, 2016 , pp. 4205-4208 More about this Journal
Abstract
Background: The aim of this study was to analyse the expression of EGFR in newly diagnosed and recurrent glioblastoma multiforme (GBM). Materials and Methods: Our study included a total of 48 paired samples collected from 24 patients diagnosed with GBM. The intensity of EGFR cytoplasmatic staining was scored on a scale of 1-3+ (weak, intermediate or strong). Results: We found EGFR overexpression in 23 patients (96%) with newly diagnosed GBM, while all recurrent tumours overexpressed EGFR. Ten recurrent tumours (42%) had a lower expression than their new counterpart 13 tumours (54%) had a similar expression, and only one case (2%) had increased expression on recurrence. The expression of EGFR in newly diagnosed GBM was significantly correlated with EGFR expression in recurrent tumour (p = 0.036). In addition, new GBMs with strong EGFR expression had a mean relapse-free interval of 11.5 months (p=0.017). A benefit of combined therapy was observed in the radiotherapy-plus-chemotherapy group where the average time was 11 months (p=0.011), as compared with surgery/radiotherapy alone (average time 6.8 months). Conclusions: The present data show that EGFR is overexpressed in paired GBMs. The discrepancies of EGFR expression between the primary tumour and the recurrence suggest heterogeneity of GBMs but also unity at relapse.
Keywords
Epidermal growth factor receptor; glioblastoma; immunohistochemistry; paired tumours;
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1 Simmons ML, Lamborn KR, Takahashi M, et al (2001). Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res, 61, 1122-8.
2 Shinojima N, Tada K, Shiraishi S, et al (2003). Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res, 63, 6962-70.
3 Snuderl M, Fazlollahi L, Le LP, et al (2011). Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell, 20, 810-7.   DOI
4 Stark AM, Witzel P, Strege RJ, et al (2003). p53, mdm2, EGFR, and msh2 expression in paired initial and recurrent glioblastoma multiforme. J Neurol Neurosurg Psychiatry, 74, 779-83.   DOI
5 Sugawa N, Yamamoto K, Ueda S, et al (1998). Function of aberrant EGFR in malignant gliomas. Brain Tumor Path, 15, 53-7.   DOI
6 Taylor TE, Furnari FB, Cavenee WK (2012). Targeting EGFR for treatment of glioblastoma: molecular basis to overcome resistance. Current Cancer Drug Target, 12, 197-209.   DOI
7 Van den Bent MJ, Gao Y, Kerkhof M, et al (2015). Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas. Neuro Oncol, 17, 935-41.   DOI
8 Vivanco I, Robins HI, Rohle D, et al (2012). Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Discov, 2, 458-71.   DOI
9 Wong AJ, Bigner SH, Bigner DD, et al (1987). Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA, 84, 6899-903.   DOI
10 Anagnostou VK, Welsh AW, Giltnane JM, et al (2010). Analytic variability in immunohistochemistry biomarker studies. Cancer Epidemiol Biomarkers Prev, 19, 982-91.   DOI
11 Montano N, Cenci T, Martini M, et al (2003). Expression of EGFRvIII in glioblastoma: prognostic significance revisited. Neoplasia, 13, 1113-21.
12 Johnson BE, Mazor T, Hong C, et al (2014). Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Sci, 343, 189-93.   DOI
13 Libermann TA, Razon N, Bartal AD, et al (1984). Expression of epidermal growth factor receptors in human brain tumors. Cancer Res, 44, 753-60.
14 Libermann TA, Nusbaum HR, Razon N, et al (1985). Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature, 313, 144-7.   DOI
15 Muallaoglu S, Besen AA, Ata A, et al (2014). Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas. Asian Pac J Cancer Prev, 3, 1333-7.
16 Nana AW, Yang PM, Lin HY (2015). Overview of transforming growth factor $\beta$ superfamily involvement in glioblastoma initiation and progression. Asian Pac J Cancer Prev, 16, 6813-23.   DOI
17 Ohgaki H, Kleihues P (2005). Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol, 64, 479-89.   DOI
18 Azuaje F, Tiemann K, Niclou SP (2015). Therapeutic control and resistance of the EGFR-driven signaling network in glioblastoma. Cell Commun Signal, 23, 13.
19 Pashaki AS, Hamed EA, Mohamadian K (2014). Efficacy of high dose radiotherapy in post-operative treatment of glioblastoma multiform--a single institution report. Asian Pac J Cancer Prev, 6, 2793-6.
20 Pelloski CE, Ballman KV, Furth AF, et al (2007). Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol, 25, 2288-94.   DOI
21 Del Vecchio CA, Giacomini CP, Vogel H, et al (2013). EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms. Oncogene, 32, 2670-81.   DOI
22 Ekstrand AJ, James CD, Cavenee WK, et al (1991). Genes for epidermal growth factor receptor, transforming growth factor $\alpha$, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res, 51, 2164-72.
23 Francis JM, Zhang CZ, Maire CL, et al (2014). EGFR variant heterogeneity in glioblastoma resolved through singlenucleus sequencing. Cancer Discov, 4, 956-71.   DOI
24 Gallego O, Cuatrecasas M, Benavides M, et al (2014). Efficacy of erlotinib in patients with replapsed glioblastoma multiforme who expressed EGFRVIII and PTEN determined by immunohistochemistry. J Neurooncol, 116, 413-9.   DOI
25 Haas-Kogan DA, Prados MD, Lamborn, KR et al (2005). Biomarkers to predict response to epidermal growth factor receptor inhibitors. Cell Cycle, 4, 1369-72.   DOI
26 Heimberger AB, Hlatky R, Suki D, et al (2005). Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res, 11, 1462-6.   DOI
27 Henriksson R, Asklund T, Poulsen HS (2011). Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review. J Neurooncol, 104, 639-46.   DOI
28 Hu X, Miao W, Zou Y, et al (2013). Expression of p53, epidermal growth factor receptor, Ki-67 and O6-methylguanine-DNA methyltransferase in human gliomas. Oncol Lett, 6, 130-134.   DOI