Comparison of immunohistochemical analysis with estrogen receptor SP1 and 1D5 monoclonal antibodies in breast cancer

Madeira, Klesia Pirola; Daltoé, Renata Dalmaschio; Sirtoli, Gabriela Modenesi; Rezende, Lucas Cunha Dias de; Carvalho, Alex Assis de; Guimarães, Isabella dos Santos; Silva, Ian Victor; Rangel, Letícia Batista Azevedo

doi:10.1016/j.prp.2012.07.010

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…A study showed an overall agreement of 96.7% between SP1 and 1D5 antibodies, but SP1 provided a better staining intensity and a better Allred score assessment. 14 Another study showed that 1D5 was less sensitive than SP1 and 6F11 and that 1D5 had a lesser power to detect ER-low-positive cases, 15 confirming similar results from a previous study. 16 A study showed that SP1 is more sensitive than 6F11 in ER-low-positive breast cancer.…”

Section: Discussionsupporting

confidence: 72%

“…Recent literature showed that rabbit monoclonal antibodies (such as SP1) are superior to mouse antibodies (such as 1D5 and 6F11). [14][15][16][17] Cutoff points used in IHC were derived from ligandbinding assays and the positivity cutoff point was previously set at Z10% of ER-positive tumor cells. 6,8,18,19 However, recent data suggest that low-ER-positive cancers (1% to 9%) may respond to endocrine therapy, 20,21 but these cancers suffer from interobserver variability.…”

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confidence: 99%

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Validation of EP1 Antibody Clone for Estrogen Receptor Immunohistochemistry in Breast Cancer

Diorio

Laberge²,

Caron³

et al. 2014

Applied Immunohistochemistry &Amp; Molecular Morphology

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Estrogen receptor (ER) tumor's status is critical for breast cancer management. A new rabbit antibody clone, EP1, is now available for ER status determination. The objective was to validate the EP1 antibody clone for its use in breast cancer ER status determination in a clinical setting against the previous standard, SP1. EP1 clone was assessed in 130 consecutive cases, including 50 ER-negative (<1% ER expression), 13 ER-low-positive (1% to 9% ER expression), and 67 ER-positive (≥10% ER expression). Using EP1 versus SP1, positive agreement (sensibility) was 92.5% and negative agreement (specificity) was 100%, leading to an overall agreement of 95.4%. All discordant cases (n=6) were ER-low-positive. SP1 was remeasured in 13 ER-low-positive and in 11 ER-negative cases. Overall agreement between SP1 initial tumor status and reassessment was 70.8% in those negative and low-positive cases. In conclusion, EP1 antibody has been validated for use in breast cancer with a positive agreement ≥90% and a negative agreement ≥95%, as recommended. Also, overall agreement between EP1 and SP1 was as good as between the SP1 initial status and SP1 reassessment.

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Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

Validation of EP1 Antibody Clone for Estrogen Receptor Immunohistochemistry in Breast Cancer

Diorio

Laberge²,

Caron³

et al. 2014

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…A few studies have shown that 8% of tumors diagnosed as ERα-negative using the 1D5 antibody were actually positive for ERα when tested with next-generation antibodies such as SP1 [29–31]. The authors did not take into account the presence of ERα46, which cannot be detected by the 1D5 antibody.…”

Section: Resultsmentioning

confidence: 99%

The AF-1-deficient estrogen receptor ERα46 isoform is frequently expressed in human breast tumors

et al. 2016

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BackgroundTo date, all studies conducted on breast cancer diagnosis have focused on the expression of the full-length 66-kDa estrogen receptor alpha (ERα66). However, much less attention has been paid to a shorter 46-kDa isoform (ERα46), devoid of the N-terminal region containing the transactivation function AF-1. Here, we investigated the expression levels of ERα46 in breast tumors in relation to tumor grade and size, and examined the mechanism of its generation and its specificities of coregulatory binding and its functional activities.MethodsUsing approaches combining immunohistochemistry, Western blotting, and proteomics, antibodies allowing ERα46 detection were identified and the expression levels of ERα46 were quantified in 116 ERα-positive human breast tumors. ERα46 expression upon cellular stress was studied, and coregulator bindings, transcriptional, and proliferative response were determined to both ERα isoforms.ResultsERα46 was expressed in over 70% of breast tumors at variable levels which sometimes were more abundant than ERα66, especially in differentiated, lower-grade, and smaller-sized tumors. We also found that ERα46 can be generated via internal ribosome entry site-mediated translation in the context of endoplasmic reticulum stress. The binding affinities of both unliganded and fully-activated receptors towards co-regulator peptides revealed that the respective potencies of ERα46 and ERα66 differ significantly, contributing to the differential transcriptional activity of target genes to 17β estradiol (E2). Finally, increasing amounts of ERα46 decrease the proliferation rate of MCF7 tumor cells in response to E2.ConclusionsWe found that, besides the full-length ERα66, the overlooked ERα46 isoform is also expressed in a majority of breast tumors. This finding highlights the importance of the choice of antibodies used for the diagnosis of breast cancer, which are able or not to detect the ERα46 isoform. In addition, since the function of both ERα isoforms differs, this work underlines the need to develop new technologies in order to discriminate ERα66 and ERα46 expression in breast cancer diagnosis which could have potential clinical relevance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0780-7) contains supplementary material, which is available to authorized users.

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“…Ideally, the assessment and interpretation of ER/PR staining would be standardized, to help ensure that results are reproducible between different observers and different laboratories regardless of reagents or staining platform used. However, a number of studies have documented significant discordant results as well as interlaboratory variability in ER assay results that have been attributed to a variety of causes, including sensitivity and specificity of antibody reagents,15–18 insufficient antigen retrieval,19–22 and differing threshold and interpretation criterion 20,23. These studies highlight the importance of rigorous and thorough evaluation of all aspects of testing, including technical validation of the performance of any new IHC staining platforms or new IHC reagents for ER and PR analysis before their clinical implementation.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Performance of Estrogen and Progesterone Receptor Antibodies on the Dako Omnis Staining Platform: Evaluation in Multicenter Studies

Dell’Orto

Falzon²,

Hoff

et al. 2017

Applied Immunohistochemistry &Amp; Molecular Morphology

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Comparison of immunohistochemical analysis with estrogen receptor SP1 and 1D5 monoclonal antibodies in breast cancer

Cited by 9 publications

References 17 publications

Validation of EP1 Antibody Clone for Estrogen Receptor Immunohistochemistry in Breast Cancer

Validation of EP1 Antibody Clone for Estrogen Receptor Immunohistochemistry in Breast Cancer

The AF-1-deficient estrogen receptor ERα46 isoform is frequently expressed in human breast tumors

Immunohistochemical Performance of Estrogen and Progesterone Receptor Antibodies on the Dako Omnis Staining Platform: Evaluation in Multicenter Studies

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