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BMC Medical Genomics

, 2:52

First Online: 12 August 2009Received: 23 January 2009Accepted: 12 August 2009


BackgroundMicroarray diagnostics of tumour samples is based on measurement of prognostic and-or predictive gene expression profiles. Typically, diagnostic profiles have been developed using bulk tumour samples with a sufficient amount of tumour cells usually >50%. Consequentially, a diagnostic results depends on the minimal percentage of tumour cells within a sample. Currently, tumour cell percentage is assessed by conventional histopathological review. However, even for experienced pathologists, such scoring remains subjective and time consuming and can lead to ambiguous results.

MethodsIn this study we investigated whether we could use transcriptional activity of a specific set of genes instead of histopathological review to identify samples with sufficient tumour cell content. Genome-wide gene expression measurements were used to develop a transcriptional gene profile that could accurately assess a sample-s tumour cell percentage.

ResultsSupervised analysis across 165 breast tumour samples resulted in the identification of a set of 13 genes which expression correlated with presence of tumour cells. The developed gene profile showed a high performance AUC 0.92 for identification of samples that are suitable for microarray diagnostics. Validation on 238 additional breast tumour samples indicated a robust performance for correct classification with an overall accuracy of 91 percent and a kappa score of 0.63 95%CI 0.47–0.73.

ConclusionThe developed 13-gene profile provides an objective tool for assessment whether a breast cancer sample contains sufficient tumour cells for microarray diagnostics. It will improve the efficiency and throughput for diagnostic gene expression profiling as it no longer requires histopathological analysis for initial tumour percentage scoring. Such profile will also be very use useful for assessment of tumour cell percentage in biopsies where conventional histopathology is difficult, such as fine needle aspirates.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-2-52 contains supplementary material, which is available to authorized users.

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Autor: Paul Roepman - Arenda Schuurman - Leonie JMJ Delahaye - Anke T Witteveen - Arno N Floore - Annuska M Glas

Fuente: https://link.springer.com/

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