Assessment of mean EGFR gene copy number is a highly reproducible method for evaluating FISH in histological and cytological cancer specimens

Zlobec, Inti and Raineri, Ines and Schneider, Sandra and Schoenegg, René and Grilli, Bruno and Herzog, Michelle and Savic, Spasenija and Bubendorf, Lukas. (2010) Assessment of mean EGFR gene copy number is a highly reproducible method for evaluating FISH in histological and cytological cancer specimens. Lung cancer, Vol. 68, H. 2. pp. 192-197.

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Official URL: http://edoc.unibas.ch/dok/A6005746

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The aims of this study were first, to systematically assess the inter-observer reproducibility of mean Epidermal Growth Factor Receptor (EGFR) gene copy number (MCN) in histological and cytological specimens from lung and non-lung cancers, second to compare the performance of this quantitative approach to the current Colorado criteria for the assessment of fluorescence in situ hybridization (FISH) positivity and third to develop a model to convert cytology into histology MCN. EGFR FISH analysis was performed on 170 histological and 153 cytological specimens. The MCN and Colorado criteria were assessed by two independent observers and agreement evaluated using Bland-Altman plots and kappa values. Conversion of cytology into histology MCN was tested on two randomized subgroups of specimens. Applying the Colorado criteria, agreement between observers was moderate with histology (k=0.5) and excellent with cytology (k=0.94). Positivity in histology versus cytology led to fair agreement (k=0.33). MCN was significantly greater in cytology compared to histology (p>0.001) with excellent inter-observer agreement in both sample types (r=0.99 and 0.89, respectively). The average difference in MCN between observers was -0.003 (95%CI: -0.05 to 0.05) and 0.008 (95%CI: -0.09 to 0.11) for cytology and histology, respectively. A reliable conversion model with an R(2)-value of 0.91 in the validation subgroup (p>0.001) was obtained. The MCN is a reproducible scoring method for evaluating EGFR FISH in samples from lung and non-lung cancers. This quantitative scoring system may constitute an alternative to current methods of gene copy number assessment and will further help to optimize patient selection for targeted therapies.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Zlobec, Inti
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Jul 2013 07:43
Deposited On:19 Jul 2013 07:35

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