Added Value of HER-2 Amplification Testing by Multiplex Ligation-dependent Probe Amplification in Invasive Breast Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Dec 11

PMID 24324739

Citations 2

Authors

Chantal C H J Kuijpers

Cathy B Moelans

Henk-Jan van Slooten

Anja Horstman

John W J Hinrichs

Shaimaa Al-Janabi

Paul J van Diest

Mehdi Jiwa

Affiliations

Soon will be listed here.

Abstract

Background: HER-2 is a prognostic and predictive marker, but as yet no technique is perfectly able to identify patients likely to benefit from HER-2 targeted therapies. We aimed to prospectively assess the added value of first-line co-testing by IHC, and multiplex ligation-dependent probe amplification (MLPA) and chromogenic in situ hybridization (CISH).

Methods: As local validation, HER-2 MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive breast cancers, from 4 Dutch pathology laboratories, that were prospectively assessed for HER-2 by IHC and MLPA (and CISH in selected cases).

Results: The validation study demonstrated 100% concordance between CISH and MLPA, if both methods were assessable and conclusive (81.8% of cases). Significant variation regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories (p<0.0001). Overall concordance between IHC and MLPA/CISH was 98.1% (575/586) (Kappa = 0.94). Of the IHC 3+ cases, 6.7% failed to reveal gene amplification, whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results remained discordant after retrospective review in 3/11 discordant cases. In the remaining 8 cases the original IHC score was incorrect or adapted after repeated IHC staining.

Conclusions: MLPA is a low-cost and quantitative high-throughput technique with near perfect concordance with CISH. The use of MLPA in routinely co-testing all breast cancers may reduce HER-2 testing variation between laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients with gene amplification, likely responsive to trastuzumab, and identify IHC 3+ cases without gene amplification that may respond less well.

Citing Articles

Breast carcinomas with low amplified/equivocal HER2 by Ish: potential supporting role of multiplex ligation-dependent probe amplification.

Ercolani C, Marchio C, Di Benedetto A, Fabi A, Perracchio L, Vici P J Exp Clin Cancer Res. 2017; 36(1):143.

PMID: 29029640 PMC: 5640946. DOI: 10.1186/s13046-017-0613-2.

Quantification of HER family receptors in breast cancer.

Nuciforo P, Radosevic-Robin N, Ng T, Scaltriti M Breast Cancer Res. 2015; 17:53.

PMID: 25887735 PMC: 4389676. DOI: 10.1186/s13058-015-0561-8.

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