Semi‐automated imaging system to quantitate estrogen and progesterone receptor immunoreactivity in human breast cancer

Sharangpani, Girish M.; Joshi, Aparna; Porter, Kyle; Deshpande, Anand; Keyhani, Sedigheh; Naik, Gurudatta; Gholap, Abhi; Barsky, Sanford H.

doi:10.1111/j.1365-2818.2007.01772.x

Cited by 49 publications

(36 citation statements)

References 13 publications

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“…Many approaches to the quantification of the ER/PR described in the literature have used various antibodies [16][17][18][19]. In the current comparative study on the ER /PR ihc expression, two types of antibodies and adequate various staining procedures were applied: the monoclonal antibodies anti-ER/anti-PR and the ER/PR pharmDx TM Kit -both products of Dako.…”

Section: Discussionmentioning

confidence: 99%

Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).

Słodkowska

Filas²,

Buszkiewicz³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:Her-2/neu is overexpressed in 20-30% of breast cancer patients and is associated with a more aggressive disease. Identification of Her-2/c-erbB-2-neu overexpression is based on immunohistochemical [ihc] detection of protein and/or gene amplification in fluorescence in situ hybridization test (FISH). Also Estrogen receptors [ER] and Progesterone receptors [PR] are the prognostic and predictive biomarkers, recently analysed by ihc methods. Subjective, manual scoring of the ihc Her-2/neu expression and expression of the ER/PR reported as the percentage of immunopositive cells are the most common mode of interpretation among pathologists. Automated microscopy and computerised processing have provided increased accuracy in quantification and standardisation. The aims of our study were: to evaluate the scoring reproducibility of Her-2 /neu ihc expression tested by two automated systems: ACIS (Dako) and ScanScope (Aperio); to estimate the ER/PR expression in ihc staining methods with different anti-ER/anti-PR antibodies (the monoclonal and the ER/PR pharmDx TM Kit ) by the ACIS system. Her-2/neu ihc expression was measured in 114 primary invasive breast carcinomas by the manual and the automated scoring (ACIS and Aperio system). 106 slides stained ihc with two types of anti-ER/anti-PR antibodies entered the quantisation. The results of our investigations showed very high reproducibility of Her-2/neu scores in intra-and interobserver analysis by ACIS evaluation. The major concordance was present in strong 3+ ihc cases; very small discordance was shown by cases with low expression of Her-2/neu. The accuracy of scoring by the Aperio was little lower in comparison to ACIS but it might result from the smaller and variable series of samples analysed by Aperio. The concordance in scoring of two automated systems was 86.5% (p<0.0001; γ=0.887); the discordance was referred only to the lower expression of Her-2/neu. The concordance in manual scoring performed by the single observer and the panel was 84.2% (p<0.0001, γ = 0.99); the discordance comprised a few cases with strong expression (2+ vs 3+). Very high intra-and interobserver reproducibility of the ER/PR ihc measurements was present in the readers results (referred to the percentage of immunoreactive carcinomatous cell population in the breast carcinomas acc. to the ACIS algorithm). No differences were disclosed in the percentage of ER-immunoreactive and PR-immunoreactive carcinomatous cell populations when used 2 different type of antibodies, in the ACIS automated method.

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Section: Discussionmentioning

confidence: 99%

Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).

Słodkowska

Filas²,

Buszkiewicz³

et al. 2010

Folia Histochem Cytobiol.

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“…[34][35][36] Rizzardi et al 37 also reported a good performance of computerassisted image classification and immunohistochemistry quantification in ovarian serous carci- noma. Our algorithms performed well in the highly varied histologic types of ovarian carcinoma, with a relatively low level of manual correction needed (B8%, data not shown).…”

Section: Discussionmentioning

confidence: 99%

Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis

et al. 2014

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The purpose of this study was to evaluate whether the membrane type 1 matrix metalloproteinase-14 (or MT1-MMP) tissue expression, as assessed visually on digital slides and by digital image analysis, could predict outcomes in women with ovarian carcinoma. Tissue microarrays from a cohort of 211 ovarian carcinoma women who underwent a debulking surgery between 1993 and 2006 at the CHU de Québec (Canada) were immunostained for matrix metalloproteinase-14. The percentage of MMP-14 staining was assessed visually and with the Calopix software. Progression was evaluated using the CA-125 and/or the RECIST criteria according to the GCIG criteria. Dates of death were obtained by record linkage with the Qué bec mortality files. Adjusted hazard ratios of death and progression with their 95% confidence intervals were estimated using the Cox model. Comparisons between the two modalities of MMP-14 assessment were done using the box plots and the Kruskal-Wallis test. The highest levels of MMP-14 immunostaining were associated with nonserous histology, early FIGO stage, and low preoperative CA-125 levels (Po0.05). In bivariate analyses, the higher level of MMP-14 expression (440% of MMP-14-positive cells) was inversely associated with progression using visual assessment (hazard ratio ¼ 0.39; 95% confidence interval: 0.18-0.82). A similar association was observed with the highest quartile of MMP-14-positive area assessed by digital image analysis (hazard ratio ¼ 0.48; 95% confidence interval: 0.28-0.82). After adjustment for standard prognostic factors, these associations were no longer significant in the ovarian carcinoma cohort. However, in women with serous carcinoma, the highest quartile of MMP-14-positive area was associated with progression (adjusted hazard ratio ¼ 0.48; 95% confidence interval: 0.24-0.99). There was no association with overall survival. The digital image analysis of MMP-14-positive area matched the visual assessment using three categories (440% vs 21-40 vs o20%). Higher levels of MMP-14 immunostaining were associated with standard factors of better ovarian carcinoma prognosis. In women with serous carcinoma, high expression of MMP-14 was associated with lower progression. Modern Pathology (2014Pathology ( ) 27, 1394Pathology ( -1404 doi:10.1038/modpathol.2014 published online 7 March 2014 Keywords: digital image analysis; immunohistochemistry; matrix metalloproteinase-14; ovarian carcinoma; prognosisIn the western world, ovarian cancer is the leading cause of death among gynecological malignancies and the fifth leading cause of cancer death. 1-3 Most patients present with advanced stage disease, partly because of its anatomic location, nonspecific symptoms, and lack of reliable screening methods. Despite a high rate of complete remission rate after radical surgery followed by taxane and platinumbased chemotherapy, relapse occurs in the majority

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“…TMAs were manually constructed from 500 cases of human breast cancer, scanned into virtual TMAs and measured algorithmically using nuclear and membrane immunocytochemical algorithms Sharangpani et al, 2007). …”

Section: Construction and Analysis Of Human Tmasmentioning

confidence: 99%

ERα signaling through slug regulates E-cadherin and EMT

et al. 2010

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The ERa signaling pathway is one of the most important and most studied pathways in human breast cancer, yet numerous questions still exist such as how hormonally responsive cancers progress to a more aggressive and hormonally independent phenotype. We have noted that human breast cancers exhibit a strong direct correlation between ERa and E-cadherin expression by immunohistochemistry, suggesting that ERa signaling might regulate E-cadherin and implying that this regulation might influence epithelial-mesenchymal transition (EMT) and tumor progression. To investigate this hypothesis and the mechanisms behind it, we studied the effects of ERa signaling in ERa-transfected ERa-negative breast carcinoma cell lines, the MDA-MB-468 and the MDA-MB-231 and the effects of ERa knockdown in naturally expressing ERa-positive lines, MCF-7 and T47D. When ERa was overexpressed in the ERa-negative lines, 17b-estradiol (E2) decreased slug and increased E-cadherin. Clones maximally exhibiting these changes grew more in clumps and became less invasive in Matrigel. When ERa was knocked down in the ERapositive lines, slug increased, E-cadherin decreased, cells became spindly and exhibited increased Matrigel invasion. ERa signaling decreased slug expression by two different mechanisms: directly, by repression of slug transcription by the formation of a corepressor complex of ligand-activated ERa, HDAC inhibitor (HDAC1), and nuclear receptor corepressor (N-CoR) that bound the slug promoter in three half-site estrogen response elements (EREs); indirectly by phosphorylation and inactivation of GSK-3b through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt). The GSK-3b inactivation, in turn, repressed slug expression and increased E-cadherin. In human breast cancer cases, there was a strong inverse correlation between slug and ERa and E-cadherin immunoreactivity. Our findings indicate that ERa signaling through slug regulates E-cadherin and EMT.

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Semi‐automated imaging system to quantitate estrogen and progesterone receptor immunoreactivity in human breast cancer

Cited by 49 publications

References 13 publications

Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).

Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).

Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis

ERα signaling through slug regulates E-cadherin and EMT

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