Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring

Rizzardi, Anthony E.; Johnson, Arthur T.; Vogel, Rachel Isaksson; Pambuccian, Stefan E.; Henriksen, Jonathan C.; Skubitz, Amy P.N.; Metzger, Gregory J.; Schmechel, Stephen C.

doi:10.1186/1746-1596-7-42

Cited by 357 publications

(283 citation statements)

References 51 publications

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“…Individual applications for each biomarker then run the scoring of positive and negative cells itself, with subcellular resolution 40 ( Figure 1). Excellent reproducibility with this and similar systems has been shown previously [41][42][43][44][45] (see specific statistics on reproducibility with the Visiopharm integrator system for each tested biomarker in Supplementary Data).…”

Section: Digital Image Analysissupporting

confidence: 74%

Digital image analysis outperforms manual biomarker assessment in breast cancer

Stålhammar

Martínez

Lippert³

et al. 2016

Modern Pathology

149

128

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In the spectrum of breast cancers, categorization according to the four gene expression-based subtypes 'Luminal A,' 'Luminal B,' 'HER2-enriched,' and 'Basal-like' is the method of choice for prognostic and predictive value. As gene expression assays are not yet universally available, routine immunohistochemical stains act as surrogate markers for these subtypes. Thus, congruence of surrogate markers and gene expression tests is of utmost importance. In this study, 3 cohorts of primary breast cancer specimens (total n = 436) with up to 28 years of survival data were scored for Ki67, ER, PR, and HER2 status manually and by digital image analysis (DIA). The results were then compared for sensitivity and specificity for the Luminal B subtype, concordance to PAM50 assays in subtype classification and prognostic power. The DIA system used was the Visiopharm Integrator System. DIA outperformed manual scoring in terms of sensitivity and specificity for the Luminal B subtype, widely considered the most challenging distinction in surrogate subclassification, and produced slightly better concordance and Cohen's κ agreement with PAM50 gene expression assays. Manual biomarker scores and DIA essentially matched each other for Cox regression hazard ratios for all-cause mortality. When the Nottingham combined histologic grade (Elston-Ellis) was used as a prognostic surrogate, stronger Spearman's rank-order correlations were produced by DIA. Prognostic value of Ki67 scores in terms of likelihood ratio χ 2 (LR χ 2 ) was higher for DIA that also added significantly more prognostic information to the manual scores (LR− Δχ 2 ). In conclusion, the system for DIA evaluated here was in most aspects a superior alternative to manual biomarker scoring. It also has the potential to reduce time consumption for pathologists, as many of the steps in the workflow are either automatic or feasible to manage without pathological expertise.

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Section: Digital Image Analysissupporting

confidence: 74%

Digital image analysis outperforms manual biomarker assessment in breast cancer

Stålhammar

Martínez

Lippert³

et al. 2016

Modern Pathology

149

128

View full text Add to dashboard Cite

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“…39 There are several possibilities for this trend. We noted that the time of sample collection and diagnosis occurred between 1985 and 1997, prior to the molecular subtyping of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…38 This method is low cost, freely available and would result in yield continuous values, possibly reducing the subjectivity commonly found in scoring. 39 Expression patterns were compared among normal breast tissues, fibroadenoma tissues, which are non-malignant breast lesions, and invasive breast carcinoma tissues. Of the invasive breast cancer cases, 91% were comprised of invasive ductal carcinoma and 9% were diagnosed as invasive lobular carcinoma.…”

Section: Ccl2 and Fsp1 Are Co-expressed In Breast Cancermentioning

confidence: 99%

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Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

Yao

Staggs

et al. 2016

Modern Pathology

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Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n = 427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR = 7.51 P = 0.007) was associated with a greater hazard than cancer stage (HR = 2.45, P = 0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.

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“…Quantification of the staining intensity was visually performed, which is a traditional method for IHS. This may be better analyzed by multiple pathologists or by using computeraided methods to avoid inter-observer or inter-institutional variations (28). If NED was otherwise determined, the results could also have been affected.…”

Section: Hspc Crpc --------------------------------------------------mentioning

confidence: 99%

The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients

Komiya

Yasuda

Watanabe

et al. 2013

Molecular and Clinical Oncology

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Abstract. Prostate cancer (PCa) is a leading cause of mortality, and despite good response to androgen ablation this response is eventually lost. In the present study, androgen receptor (AR) expression and neuroendocrine differentiation (NED) were evaluated in hormone-sensitive (HSPC) and castration-resistant prostate cancers (CRPC). Prostate tissues were obtained from 20 HSPC patients at diagnosis and 28 CRPC patients at castration-resistant progression. AR, chromogranin A (CGA) and neuron-specific enolase (NSE) were evaluated by immunohistochemical staining (IHS) in representative positive cores for PCa. IHS intensity was graded as negative, 0; positive, 1+ and strongly positive, 2+. The proportion of the 1+ and 2+ areas in PCa cells was determined. PCa was considered to be in NED if ≥50% of the tumor cells were 1+ or 2+ for CGA or NSE. The observed IHS intensity (0/1+/2+) for AR, CGA and NSE was 0/4/16, 5/11/4 and 11/4/5 in HSPC patients and 9/3/16, 5/8/15

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Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring

Cited by 357 publications

References 51 publications

Digital image analysis outperforms manual biomarker assessment in breast cancer

Digital image analysis outperforms manual biomarker assessment in breast cancer

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients

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