Objective measurement of breast cancer oestrogen receptor status through digital image analysis

Mofidi, R.; Walsh, Robert J.; Ridgway, Paul F.; Crotty, Thomas B.; McDermott, Enda; Keaveny, T. V.; Duffy, MichaelJ.; Hill, A. D. K.; O’Higgins, N.

doi:10.1053/ejso.2002.1373

Cited by 52 publications

(38 citation statements)

References 12 publications

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“…Even specialized pathologists differ in the interpretation of the specimens (21). Immunohistochemistry is a qualitative method, however, it has recently being quantitatively evaluated with the use of digital analysis software (22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

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Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

et al. 2013

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Introduction:The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods: This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: The mean follow-up time was 7.9 years (range 1.9 to 19.5 years).The analysis of CA-IX expression against the selected prognostic parameters showed no correlation.

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Section: Discussionmentioning

confidence: 99%

“…Adobe Photoshop® is a widely available, low cost software, and its use makes this technology available and reproducible to other centers (16,17,(25)(26)(27). The gene that codifies CA-IX is regulated by HIF-1α expression, and HIF-1α is controlled by the VHL protein.…”

Section: Discussionmentioning

confidence: 99%

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

et al. 2013

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“…It has been shown that it is feasible to quantify ER and/or PR signals using different proprietary instruments [16][17][18] or even relatively simple microcomputer-based image analysis techniques. 19,20 Recent published studies showing a dichotomized, bimodal distribution of ER expression using the 1D5 monoclonal antibody have called into question the necessity of quantification, suggesting that ER is almost always either completely positive or completely negative. 4,21 Inasmuch as not all ER-positive patients respond to endocrine therapy, and because ER appears, for example, by ligand-binding assays to be a continuous rather than binary parameter in breast, it is not yet clear that one should discard the notion of quantification of ER and PR analysis by IHC.…”

Section: Choice Of Antibodymentioning

confidence: 99%

Current issues in ER and HER2 testing by IHC in breast cancer

2008

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The presence of estrogen receptors (ERs), as detected by immunohistochemistry (IHC), is a weak prognostic marker of clinical outcome in breast cancer, but a strong predictive marker for response, for example, to tamoxifen-based therapy. As with all IHC markers, factors such as tissue fixation (both type and duration), the choice of antibody, and the threshold for interpretation of positive immunostaining can dramatically affect test accuracy and reproducibility. For example, optimal fixation for detection of ER requires at least 6-8 h in formalin, and the use of newer antibodies such as SP1 may identify additional patients who might benefit from hormonal therapy. Although the threshold for positivity may be as few as 1% of tumor cells showing nuclear signal, recent studies appear to demonstrate a dichotomization of ER IHC, with the vast majority of cases showing all positive or all negative results. This may be helpful in dictating the appropriateness of hormonal therapy, but quantification of ER by IHC, or other methods, may play a more important role in the future. Breast cancers with human epidermal receptor protein-2 (c-erbB-2; HER2) alterations are critical to identify because such tumors require unique treatment, including the use of targeted therapies such as trastuzumab. HER2 alterations at the DNA (amplification) and protein (overexpression) level usually occur in concert, and both fluorescence in situ hybridization (FISH) or IHC can be accurate methods to assess these alterations. However, recent studies have suggested that serious reproducibility issues exist in both FISH and IHC HER2 studies. To address this, a joint committee of both the American Society for Clinical Oncologists and the College of American Pathologists has promulgated new guidelines for HER2 testing. These include the following: (a) recommendations for tissue fixation for more than 6 and less than 48 h; (b) new scoring criteria, including a new threshold of 30% strong immunostaining for classification of 3 þ ; (c) introduction of the term 'equivocal' to characterize HER2 studies that are 2 þ by IHC and/or show HER2/chromosome 17 ratios of between 1.8 and 2.2 by FISH; (d) requirements for laboratories to validate HER2 assays, generally through the cross-testing of cases with another HER2 methodology, with laboratories required to attain 95% concordance for both positive and negative tests; (e) participation in HER2 proficiency testing.

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“…These parameters are used to reduce the effect of local variations in slide preparation and image acquisition on nuclear measurements. This system is superior to commercially available image analysis software, such as Adobe Photoshop, [70] Optimas, [42] and Image Pro Plus, [71] which contain macros that allow semi-automated image analysis. User interaction is required for object (nuclei) selection, modification of object boundaries, and/or selection of thresholds.…”

Section: Quantitative Image Analysis For Androgen Receptormentioning

confidence: 99%

A role for the androgen-receptor in clinically localized and advanced prostate cancer

Mohler

2008

Best Practice & Research Clinical Endocrinology & Metab

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Earlier studies of androgen-receptor (AR) expression using frozen prostate tissue, and later studies using archived specimens, produced the consensus that ligand-stabilized AR is nuclear, AR expression is similar in benign epithelia and stroma, AR expression is greater in secretory epithelia than basal cells, and AR expression is more variable in prostate cancer (CaP) than in benign prostatic hyperplasia (BPH). Accurate measurement of AR expression remains technically challenging but necessary to evaluate the relevance of ARs to clinical CaP. Recent studies demonstrated that AR expression in epithelia and stroma may be prognostic in clinically localized CaP, and AR expression may play a role in racial differences in CaP mortality and predict response to androgen deprivation therapy. High levels of AR and AR-regulated gene expression indicate a central role for AR in growth regulation of castration-recurrent CaP. New treatments for the lethal phenotype of CaP require better understanding of AR transactivation during androgen deprivation therapy. Keywordsandrogen receptor; prostate cancer; quantitative video image analysis; immunohistochemistry Androgens are necessary for the development and growth of the prostate and for the development, growth and progression of prostate cancer (CaP). An American man is diagnosed with CaP every 3 minutes,[1] and the worldwide incidence of CaP is increasing an estimated 1.1% annually.[2] Despite increased use of digital rectal examination and serum prostatespecific antigen (PSA) measurement for early detection, approximately 30% of men treated with curative intent suffer CaP recurrence. These men, and those who present with locally advanced or metastatic CaP, can be palliated by androgen deprivation therapy (ADT), which causes regression of androgen-dependent CaP through programmed cell death.[3] Although there are many methods for medical and surgical ADT, the results of ADT remain unimproved since its discovery more than 60 years ago.[4] More than 80% of men with disseminated CaP demonstrate clinical or biochemical response that is associated with a mean life expectancy of approximately 3.5 years, in contrast to non-responders or untreated patients who live an average of 9 months. Regardless of the androgen responsiveness of incurable CaP, almost all patients succumb to castration-recurrent CaP because it responds poorly to all known therapies, and

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Objective measurement of breast cancer oestrogen receptor status through digital image analysis

Cited by 52 publications

References 12 publications

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

Current issues in ER and HER2 testing by IHC in breast cancer

A role for the androgen-receptor in clinically localized and advanced prostate cancer

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