Detection of HER2 Amplification in Breast Carcinomas: Comparison of Multiplex Ligation‐Dependent Probe Amplification (MLPA) and Fluorescence In Situ Hybridization (FISH) combined with Automated Spot Counting

Moerland, Elna; Hezik, Rens L. H. P. M. van; Aa, Toine C. J. M. van der; Beek, M.W.P.M. van; Brule, Adriaan J. C. van den

doi:10.1155/2006/741586

Cited by 19 publications

(11 citation statements)

References 21 publications

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“…However, because we considered a HER2 score of 2+ to be HER2- due to a lack of FISH amplification information for the study period, we cannot exclude the possibility that the HER2 positivity was underestimated, which would influence the incidence of both the luminal B and HER2-overexpression subtypes. However, it has been shown in various studies that approximately 25 to 50% of HER2 2+ tumors are positive by FISH amplification [ 28 , 29 ], and this value may provide a better estimation of the molecular subtype distribution in this study population.…”

Section: Discussionmentioning

confidence: 97%

A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population

Lim

Park

et al. 2014

World J Surg Onc

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BackgroundTo investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype.MethodsWe compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n = 14,547) and ILC (n = 528).ResultsThe ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype.ConclusionsSimilar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.

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Section: Discussionmentioning

confidence: 97%

A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population

Lim

Park

et al. 2014

World J Surg Onc

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“…Review of the 11 discordant cases revealed true discordance in only 3 cases, while in the remainder the original IHC score was incorrect or adapted after repeated IHC staining. Discordance between protein expression and gene amplification described by others ranged from 0% to 11.5% IHC negative/amplified tumors and from 0% to 21.9% IHC positive/non-amplified tumors [7] ; [10] – [12] ; [15] – [18] .…”

Section: Discussionmentioning

confidence: 85%

“…HER-2 protein expression and gene amplification are not in complete accordance. Previous studies have demonstrated IHC 0/1+ breast cancers with HER-2 gene amplification as well as IHC 3+ cases without gene amplification [7] ; [10] – [12] ; [15] – [19] . Therefore, in April 2011 we at Symbiant B.V. started co-testing for HER-2 with IHC and MLPA in every invasive breast cancer case, instead of only the equivocal cases.…”

Section: Introductionmentioning

confidence: 96%

“…A cost-effective, easy-to-perform and quantitative high-throughput technique for routinely assessing HER-2 gene amplification status may be the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique. Moerland et al [10] first described MLPA for the use of HER-2 gene amplification detection in 2006. In their study and in other studies, MLPA has proven to be a reliable, less expensive and high-throughput alternative, highly concordant with ISH [11] – [14] .…”

Section: Introductionmentioning

confidence: 99%

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

Kuijpers¹,

Moelans

Slooten³

et al. 2013

PLoS ONE

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BackgroundHER-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).MethodsAs 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).ResultsThe 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.ConclusionsMLPA 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.

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“…All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification, with a 98% overall concordance of detection of Her2 gene amplification by FISH and MLPA. Also in this case, authors concluded that MLPA is a reliable and reproducible technique that can be used either as an alternative or additional test to determine HER2 status in breast carcinomas [ 122 ]. These results were confirmed on a larger series by the same group, who compared MLPA, FISH and chromogenic in situ hybridization (CISH) in the assessment of the HER-2/neu gene amplification status with protein overexpression by IHC in 518 breast carcinoma patients.…”

Section: Mlpa Applications In Genetic Testingmentioning

confidence: 99%

Use of the MLPA Assay in the Molecular Diagnosis of Gene Copy Number Alterations in Human Genetic Diseases

Stuppia

Antonucci

Palka

et al. 2012

IJMS

204

140

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Multiplex Ligation-dependent Probe Amplification (MLPA) assay is a recently developed technique able to evidence variations in the copy number of several human genes. Due to this ability, MLPA can be used in the molecular diagnosis of several genetic diseases whose pathogenesis is related to the presence of deletions or duplications of specific genes. Moreover, MLPA assay can also be used in the molecular diagnosis of genetic diseases characterized by the presence of abnormal DNA methylation. Due to the large number of genes that can be analyzed by a single technique, MLPA assay represents the gold standard for molecular analysis of all pathologies derived from the presence of gene copy number variation. In this review, the main applications of the MLPA technique for the molecular diagnosis of human diseases are described.

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Detection of HER2 Amplification in Breast Carcinomas: Comparison of Multiplex Ligation‐Dependent Probe Amplification (MLPA) and Fluorescence In Situ Hybridization (FISH) combined with Automated Spot Counting

Cited by 19 publications

References 21 publications

A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population

A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population

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

Use of the MLPA Assay in the Molecular Diagnosis of Gene Copy Number Alterations in Human Genetic Diseases

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