Concordance of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Using Tissue Microarray in Breast Cancer

Furrer, Daniela; Jacob, Simon; Caron, Catherine; Sanschagrin, François; Provencher, Louise; Diorio, Caroline

doi:10.21873/anticanres.11701

Cited by 9 publications

(8 citation statements)

References 36 publications

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“…Strict adherence to the testing algorithm resulted in a 100% agreement between protein overexpression defined by a 3+ IHC score and gene amplification by dc-ISH, whereas none of the cases with equivocal IHC result was accompanied by gene amplification. A similarly high concordance rate has been reported for breast cancer before [38]. Inconsistencies between HER2 overexpression and gene amplification may be attributed to gene dysregulation as another mechanism resulting in increased protein levels.…”

Section: Discussionsupporting

confidence: 70%

HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis

et al. 2019

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BackgroundCholangiocarcinoma is a rapidly fatal cancer entity with a median survival of less than one year. In contrast to many other malignancies, no substantial therapeutic breakthrough has been made in the past few decades, thereby limiting the treatment to cytotoxic chemotherapy with little beneficial effect for most patients. Targeted therapy tailored to the individual has shown substantial success in the recent past as a promising avenue for cancer therapy.MethodsIn this study, we determined the frequency of amplification of the HER2 gene in a comprehensive and well-characterized European cholangiocarcinoma cohort encompassing 436 patients including intrahepatic (n = 155), proximal (n = 155) and distal (n = 126) cholangiocarcinoma by strict application of a combined immunohistochemical and in situ hybridization algorithm following the current guidelines for HER2 assessment in gastric cancer.ResultsWe identified a proportion of 1.4% (n = 6) patients that demonstrated HER2 gene amplification, with the highest rate among the distal cholangiocarcinoma patients (2.4%). None of the patients with equivocal (2+) immunohistochemical staining results exhibited gene amplification molecularly. In four of the five patients with HER2 positivity, gene amplification was already present in concomitantly tested high-grade biliary intraepithelial neoplasia (80%). HER2 gene amplification was not significantly associated with other clinical parameters, including survival.ConclusionsThis study identifies HER2 gene amplification as a rare event in cholangiocarcinoma of the Western population, occurring already in high-grade BilIN in a subset of patients. Furthermore, we provide a robust testing algorithm that may be used prior to therapy administration in future clinical trials evaluating the role of HER2 as a predictive marker in cholangiocarcinoma.

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Section: Discussionsupporting

confidence: 70%

HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis

et al. 2019

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“…Patients were recruited consecutively between 2011 and 2012 at the Centre des maladies du sein (CMS) de Québec to obtain a representative cohort of the CMS attendees [33]. For this cohort, 558 patients were recruited.…”

Section: Cohort Recruitment and Tissue Micro Array Constructionmentioning

confidence: 99%

Trastuzumab effects depend on HER2 phosphorylation in HER2-negative breast cancer cell lines

et al. 2020

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The breast cancer (BC) biomarker HER2 (Human Epidermal Receptor 2) is overexpressed in 25% of BC. Only patients with HER2-positive tumors receive HER2-targeting therapies, like trastuzumab (Herceptin). However, some women with a HER2-negative BC could benefit from trastuzumab. This could be explained by the activation/phosphorylation of HER2 that can be recognized by trastuzumab. The aim of this study is to examine trastuzumab effects on HER2 phosphorylation at tyrosine Y877 (pHER2 Y877). HER2 and pHER2 Y877 status were evaluated in a cohort of BC patients representative of molecular subtypes distribution (n = 497) and in a series of BC cell lines (n = 7). Immunohistochemistry against pHER2 Y877 was performed on tissue micro arrays. Cellular proliferation assays were performed on BC cell lines presenting different combinations of HER2 and pHER2 Y877 status and treated with increasing doses of trastuzumab (0-150 μg/ml). The prevalence of pHER2 Y877 in this cohort was 6%. Nearly 5% of patients with HER2-negative tumors (n = 406, 82%) overexpressed pHER2 Y877. Among triple negative BC patients (n = 39, 8%), 7.7% expressed pHER2 Y877. Trastuzumab treatment decreased cell proliferation in HER2 −/pHER2 Y877 + BC cell lines, to an extent comparable to what occurs in HER2+ cell lines, but did not affect HER2−/pHER2 Y877 − cell lines. Trastuzumab sensitivity in HER2 −/pHER2 Y877 + cell line is specific to HER2 tyrosine 877 phosphorylation. Hence, with further confirmation in a bigger cohort, trastuzumab treatment could be envisaged as a treatment option to women presenting with HER2−/pHER2+ tumors, representing more than 1000 BC women in Canada in 2019.

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“…A good concordance rate between IHC and FISH test for HER2 in breast cancers has been reported 11–13 . As a result, in clinical practice, only those patients with IHC 2+ are referred for FISH analysis to determine the HER2 gene status in our institution.…”

Section: Discussionmentioning

confidence: 90%

Impact of the 2018 ASCO/CAP guidelines on HER2 fluorescence in situ hybridization interpretation in invasive breast cancers with immunohistochemically equivocal results

Wang

Ding

Sun

et al. 2019

Sci Rep

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The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recently issued updated guidelines on human epidermal growth factor receptor 2 (HER2) testing by fluorescence in situ hybridization (FISH) in invasive breast cancers. In this study, we aimed to investigate the impact of the new recommendations on HER2 FISH interpretation in invasive breast cancers with immunohistochemically (IHC) equivocal results. 1810 breast cancer cases with IHC equivocal results were enrolled in this study between January 2012 and May 2019. Concomitant IHC was performed on the same tissue blocks detected by FISH testing. According to the 2018 guidelines, all the cases in ISH group 2 were categorized as HER2 negative; three of four cases in ISH group 3 were considered as HER2 positive, while the one scored IHC 1+ was reclassified as HER2 negative; Fifty-three previously ISH equivocal cases were redistributed into ten HER2-positive cases and forty-three HER2-negative cases. In conclusion, the utility of 2018 ASCO/CAP guidelines resulted in a slight decrease in HER2 positive rate, due to the reclassification of cases in ISH group 2 and group 4. The implementation of the new guidelines can reduce reflex FISH test and make the diagnosis of HER2 gene status more definitive.

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Concordance of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Using Tissue Microarray in Breast Cancer

Abstract: Since some cases were discordant, we suggest that both methods be used for HER2 assessment. The lower concordance rate between diagnostic and additional blocks using IHC compared to FISH suggests a greater variability of IHC staining across tumor regions than for FISH results.

Cited by 9 publications

References 36 publications

HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis

HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis

Trastuzumab effects depend on HER2 phosphorylation in HER2-negative breast cancer cell lines

Impact of the 2018 ASCO/CAP guidelines on HER2 fluorescence in situ hybridization interpretation in invasive breast cancers with immunohistochemically equivocal results

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