title: Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization: association with clinicopathological features and patient survival.
abstract: Chromogenic in situ hybridization (CISH) was used to detect amplification of the epidermal growth factor receptor (EGFR) gene in tissue microarrays of tumours derived from 287 patients with grade II-IV diffuse astrocytomas. Amplification was found in 32% of the tumours with a highly significant association with histological grade (4% in grade II, 21% in grade III and 39% in grade IV; P < 0.001). Amplification of the EGFR gene was more common in primary than in secondary glioblastomas (41%vs. 16%, P = 0.033). Overexpression of EGFR mRNA and protein (wild-type and vIII variant) was found to correlate with EGFR gene amplification (P = 0.028, P = 0.035 and P = 0.014 respectively), but wild-type EGFR protein was also frequently overexpressed in tumours without EGFR gene amplification. Patients with older age (P < 0.001) and tumours with lack of p53 overexpression (P = 0.03) and higher apoptosis rate (P < 0.001) had significantly more EGFR gene amplifications than their counterparts. No such correlation with apoptosis was found in glioblastomas. The survival of patients with EGFR gene-amplified grade III tumours was significantly shorter than in those with grade III non-amplified tumours (P = 0.03). No such difference was noted in glioblastomas (grade IV tumours). Our data verify the central role of EGFR in the pathobiology of astrocytic tumours, and highlight the advantages of CISH as a simple and practical assay to screen for EGFR gene amplification in astrocytic tumours.
authors.affiliation: Department of Pathology, Tampere University Hospital, Tampere, Finland. sally.jarvela@sci.fi
authors.forename: Sally
authors.initials: S
authors.lastname: Järvelä
authors.forename: S
authors.initials: S
authors.lastname: Järvellä
authors.forename: H
authors.initials: H
authors.lastname: Helin
authors.forename: J
authors.initials: J
authors.lastname: Haapasalo
authors.forename: Timo
authors.initials: T
authors.lastname: Järvelä
authors.forename: T
authors.initials: T
authors.lastname: Järvellä
authors.forename: T T
authors.initials: TT
authors.lastname: Junttila
authors.forename: K
authors.initials: K
authors.lastname: Elenius
authors.forename: M
authors.initials: M
authors.lastname: Tanner
authors.forename: H
authors.initials: H
authors.lastname: Haapasalo
authors.forename: J
authors.initials: J
authors.lastname: Isola
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002863:Chromogenic Compounds; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53
chemical_list: D002863:Chromogenic Compounds; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors