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Immunohistochemical expression of EGFR in colorectal carcinoma correlates with high but not low level gene amplification, as demonstrated by CISH

Hemmings, Christine; Broomfield, Amy; Bean, Elaine; Whitehead, Martin; Yip, Desmond

Description

Aim: To assess and compare immunohistochemical expression of epidermal growth factor receptor EGFR with gene amplification as demonstrated by chromogenic in situ hybridisation CISH, in colorectal adenocarcinoma. Methods: Sections from 100 consecutive colorectal cancer resection specimens were stained for EGFR using immunohistochemistry and CISH. Immunohistochemical assessment was independently performed at two laboratories, using the same antibody and protocols. Results: With...[Show more]

dc.contributor.authorHemmings, Christine
dc.contributor.authorBroomfield, Amy
dc.contributor.authorBean, Elaine
dc.contributor.authorWhitehead, Martin
dc.contributor.authorYip, Desmond
dc.date.accessioned2015-12-08T22:36:23Z
dc.identifier.issn0031-3025
dc.identifier.urihttp://hdl.handle.net/1885/35233
dc.description.abstractAim: To assess and compare immunohistochemical expression of epidermal growth factor receptor EGFR with gene amplification as demonstrated by chromogenic in situ hybridisation CISH, in colorectal adenocarcinoma. Methods: Sections from 100 consecutive colorectal cancer resection specimens were stained for EGFR using immunohistochemistry and CISH. Immunohistochemical assessment was independently performed at two laboratories, using the same antibody and protocols. Results: With immunohistochemistry, strong circumferential membrane staining 3 staining was demonstrated in only 5 of cases, and this was only focal in three of five cases. At one laboratory, weak or incomplete staining 1 or 2 was observed in five further cases 5, which had been negative at the other laboratory. CISH demonstrated high level gene amplification >10 copiesnucleus in the same five cases which had demonstrated 3 staining with immunohistochemistry, and in those cases where the staining was focal, the amplification was demonstrated in the same foci of the tumour. Five further cases 5 had low level amplification 510 copies per nucleus; these cases did not exhibit significant positive staining with immunohistochemistry. All the cases which demonstrated gene amplification high or low level arose in the distal colon. There was no correlation between gene amplification status and a variety of other variables, including stage at diagnosis, mucinous differentiation, neuroendocrine differentiation, or loss of expression of mismatch repair proteins. Conclusions: Immunohistochemical expression of EGFR is variable between laboratories, even using standardised protocols. 3 staining is predictive of high level gene amplification, but correlates very poorly with low level amplification, which may still be clinically significant. In some cases gene amplification was only focal, offering a potential explanation for poor response to targeted therapy in patients with EGFR positive tumours.
dc.publisherTaylor & Francis Group
dc.sourcePathology
dc.subjectKeywords: epidermal growth factor receptor; mismatch repair protein; adult; aged; article; cancer staging; cancer surgery; clinical assessment; colorectal carcinoma; controlled study; descending colon; female; gene amplification; histopathology; human; human tissue CISH; Colorectal carcinoma; EGFR; Gene amplification
dc.titleImmunohistochemical expression of EGFR in colorectal carcinoma correlates with high but not low level gene amplification, as demonstrated by CISH
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume41
dc.date.issued2009
local.identifier.absfor111201 - Cancer Cell Biology
local.identifier.ariespublicationu4201517xPUB122
local.type.statusPublished Version
local.contributor.affiliationHemmings, Christine, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBroomfield, Amy, Canberra Hospital
local.contributor.affiliationBean, Elaine, Canberra Hospital
local.contributor.affiliationWhitehead, Martin, Canterbury Health Laboratories
local.contributor.affiliationYip, Desmond, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue4
local.bibliographicCitation.startpage356
local.bibliographicCitation.lastpage360
local.identifier.doi10.1080/00313020902884477
dc.date.updated2016-02-24T10:40:34Z
local.identifier.scopusID2-s2.0-68849106333
CollectionsANU Research Publications

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