Issues and updates: evaluating estrogen receptor-α, progesterone receptor, and HER2 in breast cancer

Allred, D. Craig

doi:10.1038/modpathol.2010.55

Cited by 174 publications

(155 citation statements)

References 73 publications

(85 reference statements)

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“…The cut-off points of ER and PR were 1% 6 and Ki-67 was 14%. 6,7 HER2 was reported according WHO guidelines 6 and 3+ staining was considered positive.…”

Section: Methodsmentioning

confidence: 99%

Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

et al. 2016

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Background: Tumor budding is a histopathologic entity refers to small cluster of cancer cells at the invasive edge of tumor. It was assumed that tumor budding is linked to epithelial-mesenchymal transition, an early event in metastasis. Objective: This study aimed to find out the correlation of tumor budding with E-cadherin and MMP-9 expression and risk of metastasis in breast carcinoma. Method: We investigated 35 cases breast carcinoma with metastasis and 35 cases without metastasis. The number of tumor budding was counted in cytokeratin-stained slides with 400x magnification (0.57 mm 2 ).Result: Cut-off point by ROC analysis was 11 and the patient was categorized into low grade (0-10 buds) and high grade (11 or more buds) tumor budding. Inter-observer agreement was good with K value 0.914. Low level of E-cadherin was not significantly correlated with high grade tumor budding (p=0.660), meanwhile high level of MMP-9 was significantly correlated with high grade tumor budding (p=0.001). High grade tumor budding was a significant, independent risk factor of metastasis in breast carcinoma (OR=38.2, 95% CI 7. 5-193.7, p<0.001). Conclusion:In conclusion, tumor budding grade is related to level of MMP-9 but has no correlation E-cadherin expression. High grade tumor budding is an independent risk factor of metastasis in breast carcinoma.

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“…The cut-off points of ER and PR were 1% 6 and Ki-67 was 14%. 6,7 HER2 was reported according WHO guidelines 6 and 3+ staining was considered positive.…”

Section: Methodsmentioning

confidence: 99%

Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

et al. 2016

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“…13 Indeed, immunohistochemistry assessment of the expression level of tumor-associated genes is already established as an integral component of existing predictive tests of clinical relevance in the treatment of breast and gastric cancer. 8,14,15 In breast cancer, guidelines recommend the use of fluorescence in situ hybridization analysis of HER2 copy number status to inform treatment decisions in relation to trastuzumab therapy for patients whose tumors are initially scored as equivocal for HER2 expression by immunohistochemistry (2þ). 16 In the case of EGFR, although as might be expected associations have been reported between increased EGFR copy number and high levels of gene expression in tumors, 2,17 a recent analysis of patients included in the phase III FLEX study did not demonstrate a predictive value for EGFR copy number in relation to the efficacy of chemotherapy plus cetuximab therapy.…”

Section: Commentmentioning

confidence: 99%

Reproducibility of Immunohistochemical Scoring for Epidermal Growth Factor Receptor Expression in Non–Small Cell Lung Cancer: Round Robin Test

Rüschoff

Kerr

Grote

et al. 2013

Archives of Pathology & Laboratory Medicine

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Context.-The addition of cetuximab to first-line chemotherapy substantially prolonged survival in patients with advanced non-small cell lung cancer whose tumors expressed high levels of epidermal growth factor receptor (EGFR; immunohistochemistry score of !200 on a scale of 0-300).Objective.-To evaluate the interobserver reproducibility of this EGFR immunohistochemistry scoring system, based on both the tumor cell membrane staining intensity (graded 0-3þ) and the percentage of cells staining at each intensity.Design.-In parts 1 (initial feasibility study) and 2 of this 2-part round robin test, sections of different non-small cell lung cancer tissue microarrays were stained in a central reference laboratory. Following reference evaluation, EGFR expression in 30 selected tumor cores was characterized in serial sections by lung cancer pathology specialists. The reproducibility of scoring by different raters was assessed. Analysis of between-rater agreement was based on the allocation of EGFR immunohistochemistry scores into low-(,200) and high-(!200) EGFR expression groups.Results.-After discussion with raters of the issues impacting reproducibility identified in part 1 and following adjustment of processes, part 2 of the round robin test showed a high interobserver agreement in EGFR immunohistochemistry scoring, with an overall concordance rate of 90.9% and a mean coefficient of 0.812. Specimens with a reference EGFR immunohistochemistry score of lower than 200 and of 200 or higher showed mean concordance rates of 94.7% and 85.6%, respectively.Conclusions.-After appropriate training, assessing EGFR expression by this immunohistochemistry-based method allowed a highly reproducible allocation of nonsmall cell lung cancers into clinically relevant high-or low-EGFR expression groups.

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“…Although the precise cause of this remains unknown, data support that it might be related to the use of hormone replacement therapy among postmenopausal women (Li et al 2003). ER, PR, and HER2 status are three important molecular features of invasive breast carcinomas that have been identified during the past 30 years, and their evaluation by pathologists is now mandatory (Allred 2010). ER and PR are growth-regulating nuclear transcription factors that are usually measured by immunohistochemistry (IHC), and the amount of protein expressed is directly related to responsiveness to endocrine therapy, which is why they are so important (Harvey et al 1999;Mohsin et al 2004).…”

Section: Histopathologymentioning

confidence: 99%

“…Cell surface levels of this membrane protein strongly associate with amplification of this oncogene, and thus HER2 status can be measured either at the protein level by IHC or at the DNA level by assessing gene copy number with assays such as fluorescence in situ hybridization. Overexpressed and/or amplified HER2 is a relatively weak prognostic factor in untreated patients, but it is a strong predictive factor for responsiveness to targeted therapies such as trastuzumab, which is the primary reason for measuring it (Ross et al 2004;Allred 2010).…”

Section: Histopathologymentioning

confidence: 99%

Breast and Ovarian Cancers

Yoneda

Lendorf

Couchman

et al. 2011

J Histochem Cytochem.

111

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SummaryTumor markers are widely used in pathology not only for diagnostic purposes but also to assess the prognosis and to predict the treatment of the tumor. Because tumor marker levels may change over time, it is important to get a better understanding of the molecular changes during tumor progression. Occurrence of breast and ovarian cancer is high in older women. Common known risk factors of developing these cancers in addition to age are not having children or having children at a later age, the use of hormone replacement therapy, and mutations in certain genes. In addition, women with a history of breast cancer may also develop ovarian cancer. Here, the authors review the different tumor markers of breast and ovarian carcinoma and discuss the expression, mutations, and possible roles of cell surface heparan sulfate proteoglycans during tumorigenesis of these carcinomas. The focus is on two groups of proteoglycans, the transmembrane syndecans and the lipid-anchored glypicans. Both families of proteoglycans have been implicated in cellular responses to growth factors and morphogens, including many now associated with tumor progression. (J Histochem Cytochem 60:9-21, 2012)

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Issues and updates: evaluating estrogen receptor-α, progesterone receptor, and HER2 in breast cancer

Cited by 174 publications

References 73 publications

Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

Reproducibility of Immunohistochemical Scoring for Epidermal Growth Factor Receptor Expression in Non–Small Cell Lung Cancer: Round Robin Test

Breast and Ovarian Cancers

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