HER-2 gene amplification by fluorescence in situ hybridization (FISH) compared with immunohistochemistry (IHC) in breast cancer: a study of 528 equivocal cases

Zhang, Han; Ren, Guoping; Wang, Xiaoling; Zhao, Jing; Yao, Huaiying; Bai, Yanfeng; Wang, Bo

doi:10.1007/s10549-012-2101-x

Cited by 15 publications

(18 citation statements)

References 23 publications

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“…Gene amplification could be demonstrated only in some of the samples that are found 2+ by IHC (Yeh). Studies have reported that FISH positivity in IHC 2+ samples varies between 7% and 89% (Ciampa et al, 2006;Rossi et al, 2006;Kuo et al, 2007;Sui et al, 2009;Goud et al, 2012;Zhang et al, 2012). Such diverse results might be due to the differences in the number of patients included in studies, centers' and/or pathologists' experience, and the test kits used.…”

Section: Discussionmentioning

confidence: 99%

HER2/neu Status in Breast Cancer Specimens: Comparison of Immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) Methods

Sağlıcan¹,

İnce²

2015

Int. J. Morphol.

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SUMMARY: HER2 amplification or overexpression is considered as disease outcome and a predictive marker of response to treatment in breast cancer. The present study aimed to compare the results of IHC and FISH for determining HER2 and to search the interpretational differences. Samples (n= 169), of which 31 were the paraffin blocks sent from outer centers, that underwent FISH analysis for HER-2 were included. Samples were re-reviewed by IHC in our laboratory. FISH test was negative in 131 (77.5%) and positive in 38 (22.5%). When those with previous IHC 0-1+ were re-reviewed, the results were found again 0-1+ and none of them was FISH positive. Inconsistency between re-reviewed IHC and previous IHC results was 25% for those with 2+ score and 11% for those with 3+ score. Consistency between IHC and FISH was 17% and 67% for previous IHC 2+ and 3+, respectively, whereas it was 23% and %75 for re-reviewed IHC 2+ and 3+, respectively. Whilst 79% of the samples evaluated as 2+ by the inexperienced pathologist were found to be 0-1+ on the re-review, all of them were FISH negative. According to our results, we suggest that samples with IHC 2+ should be re-reviewed by consulting with an experienced pathologist.

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Section: Discussionmentioning

confidence: 99%

HER2/neu Status in Breast Cancer Specimens: Comparison of Immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) Methods

Sağlıcan¹,

İnce²

2015

Int. J. Morphol.

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“…In the literature, the incidence of amplification in IHC (++) cases have been reported as 6-25% (10,11). ASCO / CAP stated this rate as 23.9% (8).…”

Section: Discussionmentioning

confidence: 99%

Problems In Determining Her2 Status In Breast Carcinoma

Pala¹,

Bayol²,

Ozguzer³

et al. 2015

J Breasth Health

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Objective: Human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in 15-25% of breast carcinomas and associated with poor outcome. Assessment of HER2 status accurately is important to select patients who will benefit from targeted therapy. Materials and Methods:In this study immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to determine the HER2 status in 308 breast carcinoma cases of which 129 were consultation. The major problems in determining HER2 status and the reasons of discordant results between methods were discussed.Results: HER2 expression was (-) in 124, (+) in 29, (++) in 92, (+++) in 63 cases. 25 of 76 cases consulted as (++) were evaluated as (++) and 15 of 35 cases consulted as (+++) were evaluated as (+++). HER2 amplification was found in 88 (28.6%) of 308 cases by FISH. 3 of 124 (-), 1 of 29 (+), 22 of 92 (++), 62 of 63 (+++) cases were amplified by FISH. The relation between HER2 expression and amplification was statistically significant (p<0.001). Centromere 17 (CEN 17) region amplification was noted in 11 cases of which 2 were (+++), 9 were (++). 6 of the 11 cases showed focal low level, 1 of them showed diffuse high level amplification. Conclusion:The concordance rate between IHC (+++) cases and FISH was 95.4% for consultation cases, 100% for our cases. The final concordance rate for both case groups was 98.4%. The possible reasons of discrepancy were triple negativity, preanalytical and analytical procedures of consultation cases and trucut samples.

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“…In breast cancer cells, it was poven that oncoprotein Her-2 was able to promote proliferative, metastatic, and prosurvival events and correlated with a poor prognosis [9,22]. Furthermore, Her-2 expression induced a resistance to chemoradiotherapy, and its inhibition by a speci�ic monoclonal antibody, trastuzumab, yields the predominant clinical activity either alone or in combination with chemotherapy in the Her-2-positive breast cancers [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

“…Among the proteins implicated in this dysregulation, Her-2 functions as a pivotal role in breast cancer cells [9][10][11]. Her-2 oncogene induces the expression of a transmembrane receptor protein structurally similar to epidermal growth factor receptor (EGFR).…”

Section: Introductionmentioning

confidence: 99%

“…Her-2 oncogene induces the expression of a transmembrane receptor protein structurally similar to epidermal growth factor receptor (EGFR). It was reported that Her-2 was over-expressed in approximately one-third of primary breast cancer, which was correlated with a poor prognosis and decreased overall or disease-free survival [9][10][11]. Her-2 over-expression is potential to enhance proliferation, metastasis, and prosurvival signals in breast cancer cell lines and to induce resistance to hormonal therapy [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Tumor Necrosis Factor a Stimulates Her-2 Cleavage by Activated Caspase-8

Zhao

Zhang

et al. 2012

Cell Physiol Biochem

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Background/Aim: Her-2 over-expression has been correlated with a poor prognosis in patients with breast cancer. Now, we explored the effect of TNF-α treatment and/or NFĸB activation on Her-2 expression in MCF-7 breast adenocarcinoma cells. Methods: Stably transfected MCF-7 cell lines with pcDNA3.0, IĸBα MT, c-FLIP/control shRNA were established by FuGENE with the supplementation of G418 (500 µg /ml). Western blot and Real-time PCR were applied to assess the expression levels of protein and mRNA of target gene. In addition, caspase-8 activity was evaluated by the incubation with a caspase-8 fluorogenic substrate, Ac-IEPD-AMC using a spectrofluorometer. Results: It was uncovered that Her-2 was a new substrate for caspase-8 and that tumor necrosis factor α (TNF-α) stimulation resulted in a caspase-8-dependent Her-2 cleavage in MCF-7 breast adenocarcinoma cells defective for nuclear factor ĸB (NFĸB) activation. We demonstrated that the antiapoptotic transcription factor NFĸB counteracted this cleavage through the induction of caspase-8 inhibitor, c-FLIP. Conclusion: we propose a novel mechanism in which NFĸB functions as a new antiapoptotic factor by counteracting TNF-α-triggered Her-2 cleavage.

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HER-2 gene amplification by fluorescence in situ hybridization (FISH) compared with immunohistochemistry (IHC) in breast cancer: a study of 528 equivocal cases

Cited by 15 publications

References 23 publications

HER2/neu Status in Breast Cancer Specimens: Comparison of Immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) Methods

HER2/neu Status in Breast Cancer Specimens: Comparison of Immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) Methods

Problems In Determining Her2 Status In Breast Carcinoma

Tumor Necrosis Factor a Stimulates Her-2 Cleavage by Activated Caspase-8

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