Epidermal growth factor receptor: An independent predictor of survival in astrocytic tumors given definitive irradiation

Zhu, An; Shaeffer, James; Leslie, Susan; Kolm, Paul; El‐Mahdi, Anas M.

doi:10.1016/0360-3016(95)02184-1

Cited by 79 publications

(34 citation statements)

References 23 publications

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“…Although some authors claim there is no association with survival, 73,74 others state that this aberration is a negative prognostic factor. 75,76 In turn, an association between EGFR overexpression and a better prognosis in older glioblastoma patients has also been reported, 25,26,33,77 in line with our observations. Noteworthy, we did not find an association between tumor cytogenetics and other disease characteristics, such as patient age 76 and tumor localization, among other features.…”

Section: Discussionsupporting

confidence: 80%

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Crespo

Vital

Nieto

et al. 2011

The Journal of Molecular Diagnostics

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Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas. ( J Mol Diagn 2011, 13: 634 -647;

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Section: Discussionsupporting

confidence: 80%

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Crespo

Vital

Nieto

et al. 2011

The Journal of Molecular Diagnostics

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“…The cytoplasmic distribution of EGFR that we and others (Jaros et al, 1992) have observed may be explained by rapid internalization of the EGF-EGFR complex or by cytoplasmic binding of EGFR to TGFa (Jaros et al, 1992). In univariate analysis, EGFR expression failed to emerge as a significant predictor of survival, in contrast to the findings of Diedrich et al (1995) and Zhu et al (1996). The latter, however, studied only irradiated tumours.…”

Section: Discussioncontrasting

confidence: 70%

MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor

Korkolopoulou

Christodoulou²,

Kouzelis³

et al. 1997

Br J Cancer

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Summary p53 and the murine double minute 2 (MDM2) oncoprotein expression was evaluated in paraffin-embedded tissue from 61 patients with central nervous system gliomas (53 astrocytomas and eight oligodendrogliomas) and related to proliferation-associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and nuclear organizer regions (NORs)] and epidermal growth factor receptor (EGFR). We used the monoclonal antibodies PC-1 0, MIB-1, DO-1, 1 Bi 0 and EGFR 113 and the colloid silver nitrate (AgNOR) technique. MDM2 and p53were co-expressed in 28% of cases. A p53-positive/MDM2-negative phenotype was observed in 15% and a p53-negative/MDM2-positive phenotype in 20% of cases. There was a positive correlation of p53 and MDM2 expression with grade and proliferation indices. Univariate analysis in the group of diffuse astrocytomas showed that older age, high histological grade, high PCNA labelling index (LI) and high AgNOR score were associated with reduced overall survival (P < 0.05). p53 LI, Ki-67 LI, AgNOR score, tumour location and grade influenced diseasefree survival (P < 0.05), whereas the only parameters affecting post-relapse survival were histological grade and Ki-67 LI (P < 0.1). Multivariate analysis revealed that age, radiotherapy, PCNA LI and p53 LI were the independent predictors of overall survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were independent predictors of disease-free survival, and grade was the only independent predictor of post-relapse survival. Our results indicate that p53 LI and MDM2 LI, EGFR expression as well as proliferation markers (PCNA and Ki-67) are useful indicators of overall and disease-free survival in diffuse astrocytoma patients.Keywords: proliferating cell nuclear antigen; Ki-67; MIB-1; AgNORs; p53; MDM2; epidermal growth factor receptor; gliomas Central nervous system (CNS) gliomas range in clinical behaviour and histological appearance from indolent well-differentiated lesions to highly anaplastic, rapidly growing neoplasms. A cardinal property of almost all types of gliomas is a propensity to recur and undergo anaplastic change (Russel and Rubinstein, 1989). A major stimulus to the study of cell proliferation in gliomas has been the widely held belief that quantification of this fundamental process will be of value in the objective categorization of these tumours. However, while cell kinetic information is an important aspect of the biology of gliomas, it has become clear that neoplastic evolution towards glioblastoma is a multistep process that involves deregulation of several genes related to both cellular proliferation and differentiation. The molecular determinants of glioma progression are still under investigation, with considerable attention directed towards the tumour-suppressor gene p53. On the basis of findings from molecular genetic analysis, Bigner and Vogelstein (1990)

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“…Two recent studies have suggested that EGFR amplification may have prognostic relevance in some circumstances. A study from Zhu et al examined EGFR expression in 71 astrocytic gliomas, predominantly anaplastic astrocytomas and glioblastomas and suggested that the percentage of cells positive for EGFR is predictive of patient survival on univariate analysis and after correcting for the effects of patient age and tumor grade (152). While this study is potentially interesting, it stands in contrast to the general consensus of other reports and may simply reflect differences in immunohistochemical approaches.…”

Section: Epidermal Growth Factor Receptor (Egfr)mentioning

confidence: 73%

Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications

Smith

Jenkins²

2000

Front Biosci

146

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Our understanding of diffuse glioma development and progression has expanded remarkably over the past decade. As the genetic alterations responsible for these tumors are identified, molecular models of glioma pathogenesis are emerging and hold great promise to explain the biologic mechanisms of these neoplasms. Although these models continue to evolve and remain highly simplified, some of the genetic alterations that they encompass appear to be prognostically useful. Among the astrocytic gliomas, age and tumor grade are the most powerful indicators of patient survival, however, a wide range of variability remains, particularly among the lowgrade and anaplastic astrocytomas. Recent reports indicate that alterations of the PTEN tumor suppressor gene are independent predictors of overall survival for anaplastic astrocytoma patients, helping to distinguish the cases with behavior resembling their more malignant counterparts, the glioblastomas.Among the oligodendroglial tumors, alterations of the 1p and 19q chromosome arms have emerged as potentially powerful predictors of overall patient survival and in vivo chemotherapeutic response, while alterations of the p16/CDKN2A tumor suppressor gene suggest shorter overall survival. As our molecular models continue to improve, through functional analyses and the identification of additional genetic contributors, we will expand our capacity to more effectively prognose these patients and to design rational therapeutic strategies. INTRODUCTIONDiffuse gliomas exhibit an inherent tendency to progress to more malignant phenotypes and a broad range of clinical behavior. Classification of diffuse gliomas by histologic subtype (figure 1) and malignancy grade (figure 2),

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Epidermal growth factor receptor: An independent predictor of survival in astrocytic tumors given definitive irradiation

Cited by 79 publications

References 23 publications

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor

Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications

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