Automated image analysis for high‐throughput quantitative detection of ER and PR expression levels in large‐scale clinical studies: The TEAM Trial Experience

Faratian, Dana; Kay, Charlene; Robson, Tammy; Campbell, Fiona; Grant, Michelle; Rea, Dan; Bartlett, John M.S.

doi:10.1111/j.1365-2559.2009.03419.x

Cited by 47 publications

(48 citation statements)

References 28 publications

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“…Staining and scoring of ER and PgR by using TMAs and the Ariol SL-50 image analysis system (Genetix, New Milton, United Kingdom) were previously validated. 19 Samples were stained in sextuplet (6 ϫ 0.6 mm 2 cores). Slides were counterstained; each TMA section was scanned, mapped to positional map, and individually assessed for tumor content (tumor areas were marked and checked and a second pathology quality-assurance assessment was performed).…”

Section: Staining Methodologymentioning

confidence: 99%

“…The actual number and percentage of cells in each category were recorded, with a minimum of 100 tumor nuclei per patient required for eligibility. Nuclear HRec staining was assessed by using a previously validated scoring algorithm, 19 with nuclei grouped into categories of negative, weak (1ϩ), moderate (2ϩ), and strong (3ϩ) nuclear staining, to generate a continuous histoscore (range, 0 to 300). The histoscore was calculated by multiplying the sum of the percentage of weakly stained cells times 1, the percentage of moderately stained cells times 2, and the percentage of strongly stained cells times 3.…”

Section: Staining Methodologymentioning

confidence: 99%

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Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial

Bartlett

Brookes

Robson

et al. 2011

JCO

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171

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A B S T R A C T PurposeThe Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor-positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen. Patients and MethodsPathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment. ResultsOf 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred Ͻ 4) and 77% were PgRrich (Allred Ն 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P ϭ .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P Ͻ .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P ϭ .002), and multivariate analyses (P Ͻ .001 and P ϭ .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. ConclusionPreferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment. Oncol 29:1531Oncol 29: -1538 J Clin

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Section: Staining Methodologymentioning

confidence: 99%

Section: Staining Methodologymentioning

confidence: 99%

Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial

Bartlett

Brookes

Robson

et al. 2011

JCO

Self Cite

171

132

View full text Add to dashboard Cite

show abstract

“…The suitability of this system has been reported previously [31,32]. Tumour epithelium was marked for analysis, and the marked areas' quality was assured by a pathologist (DF).…”

Section: Evaluation Of Immunostainingmentioning

confidence: 99%

COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients

Nes

Kruijf

Faratian

et al. 2010

Breast Cancer Res Treat

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In breast cancer, the prognostic impact of COX2 expression varies widely between studies. We examined the prognostic value of COX2 expression in a large cohort of breast cancer patients treated with primary surgery between 1985 and 1994 and explained the variable results of COX2 expression found in the literature. A tissue microarray was constructed of available tumour material, and ER, PgR, HER2, Ki67 and COX2 were examined by immunohistochemistry. Median follow-up was 19 years. Fifty-five percent (n = 369/677) of patients received no systemic treatment. COX2 was scored using a weighted histoscore. Analysis of COX2 expression in two groups based on the median (148; below vs. above) showed an increased hazard ratio (HR) of 1.35 (95% CI 1.05-1.75, P = 0.021) for disease-free survival (DFS) and of 1.39 (95% CI 1.03-1.82, P = 0.016) for overall survival (OS). However, COX2 did not remain independent in multivariate analysis. In patients with hormone receptor positive tumours, COX2 expression had a negative influence on outcome (low vs. high: DFS: HR 1.37, 95% CI 1.07-1.76, P = 0.013). This effect disappeared when endocrine therapy was administered (low vs. high: DFS: HR 0.93, 95% CI 0.51-1.70, P = 0.811) while it remained statistically significant when endocrine therapy was omitted (low vs. high: DFS: HR 1.48, 95% CI 1.12-1.94, P = 0.005). Our results show that COX2 plays a role in hormonal pathways. Our results can explain the results found in previously published studies.

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“…Several groups have targeted this dilemma by developing automated image analysis techniques with excellent correlations to manual scoring. [6][7][8][9] Our group has previously reported that b-microseminoprotein (MSMB) and the MSMB-binding protein cysteine-rich secretory protein-3 (CRISP3) are independent predictors of patient outcome after radical prostatectomy.…”

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confidence: 99%

Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis

et al. 2011

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Despite prostate cancer being the most frequent cancer in men in the Western world, tissue biomarkers for predicting disease recurrence after surgery have not been incorporated into clinical practice. Our group has previously identified b-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) as independent predictors of biochemical recurrence after radical prostatectomy. The purpose of the present study was to use automated image analysis, enabling quantitative determination of MSMB and CRISP3 expressions in a large cohort and to validate the previous findings. MSMB and CRISP3 protein expressions were assessed on tissue microarrays constructed from 3268 radical prostatectomy specimens. Whole-slide digital images were captured, and a novel cytoplasmic algorithm was used to develop a quantitative scoring model for cytoplasmic staining. Classification regression tree analysis was used to group patients, with different risk for biochemical recurrence, depending on level of protein expression. Patients with tumors expressing high levels of MSMB had a significantly reduced risk for biochemical recurrence after radical prostatectomy (HR ¼ 0.468; 95% CI 0.394-0.556; Po0.001). Multivariate analysis adjusted for clinicopathological parameters revealed that MSMB expression was an independent predictor of decreased risk of recurrence (HR ¼ 0.710; Po0.001). We found no correlation between CRISP3 expression and biochemical recurrence. In this current study, we applied a novel image analysis on a large independent cohort and successfully verified that MSMB is a strong independent factor, predicting favorable outcome after radical prostatectomy for localized prostate cancer.

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Automated image analysis for high‐throughput quantitative detection of ER and PR expression levels in large‐scale clinical studies: The TEAM Trial Experience

Abstract: Semiautomated image analysis is appropriate for the analysis of tissue biomarkers within large clinical trials. These data provide support for the use of TMAs and image analysis in translational research.

Cited by 47 publications

References 28 publications

Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial

Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial

COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients

Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis

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