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Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor β2 immunohistochemistry in prostate cancer.

Rizzardi AE, Zhang X, Vogel RI, Kolb S, Geybels MS, Leung YK, Henriksen JC, Ho SM, Kwak J, Stanford JL, Schmechel SC - Diagn Pathol (2016)

Bottom Line: Two independent analysis runs were performed to evaluate reproducibility.For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99).After adjusting for clinicopathologic factors, only total malignant epithelial area ERβ2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Washington, 908 Jefferson Street, Room 2NJB244, Seattle, WA, 98104, USA.

ABSTRACT

Background: Digital image analysis offers advantages over traditional pathologist visual scoring of immunohistochemistry, although few studies examining the correlation and reproducibility of these methods have been performed in prostate cancer. We evaluated the correlation between digital image analysis (continuous variable data) and pathologist visual scoring (quasi-continuous variable data), reproducibility of each method, and association of digital image analysis methods with outcomes using prostate cancer tissue microarrays (TMAs) stained for estrogen receptor-β2 (ERβ2).

Methods: Prostate cancer TMAs were digitized and evaluated by pathologist visual scoring versus digital image analysis for ERβ2 staining within tumor epithelium. Two independent analysis runs were performed to evaluate reproducibility. Image analysis data were evaluated for associations with recurrence-free survival and disease specific survival following radical prostatectomy.

Results: We observed weak/moderate Spearman correlation between digital image analysis and pathologist visual scores of tumor nuclei (Analysis Run A: 0.42, Analysis Run B: 0.41), and moderate/strong correlation between digital image analysis and pathologist visual scores of tumor cytoplasm (Analysis Run A: 0.70, Analysis Run B: 0.69). For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99). Further, ERβ2 staining was significantly associated with increased risk of prostate cancer-specific mortality (PCSM) when quantified by cytoplasmic digital image analysis (HR 2.16, 95 % CI 1.02-4.57, p = 0.045), nuclear image analysis (HR 2.67, 95 % CI 1.20-5.96, p = 0.016), and total malignant epithelial area analysis (HR 5.10, 95 % CI 1.70-15.34, p = 0.004). After adjusting for clinicopathologic factors, only total malignant epithelial area ERβ2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012).

Conclusions: Digital methods of immunohistochemical quantification are more reproducible than pathologist visual scoring in prostate cancer, suggesting that digital methods are preferable and especially warranted for studies involving large sample sizes.

No MeSH data available.


Related in: MedlinePlus

Probability of PCa RFS and PCSM for ERβ2 staining quantified by image analysis. Kaplan-Meier plot for PCa recurrence-free survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (a), tumor nuclei (c), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (e). Kaplan-Meier plot for PCa-specific survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (b), tumor nuclei (d), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (f)
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Fig4: Probability of PCa RFS and PCSM for ERβ2 staining quantified by image analysis. Kaplan-Meier plot for PCa recurrence-free survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (a), tumor nuclei (c), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (e). Kaplan-Meier plot for PCa-specific survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (b), tumor nuclei (d), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (f)

Mentions: Kaplan-Meier analysis demonstrated that ERβ2 quantified by total malignant epithelial area image analysis was borderline associated with time to recurrence in univariate analysis (p = 0.057; Table 4 and Fig. 4). ERβ2 quantified separately by cytoplasmic image analysis and nuclear image analysis were not significantly associated with time to recurrence in univariate or multivariate analysis (adjusted for clinicopathologic features including age at diagnosis, Gleason score, pathologic stage, and diagnostic PSA level; Table 4 and Fig. 4).Table 4


Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor β2 immunohistochemistry in prostate cancer.

Rizzardi AE, Zhang X, Vogel RI, Kolb S, Geybels MS, Leung YK, Henriksen JC, Ho SM, Kwak J, Stanford JL, Schmechel SC - Diagn Pathol (2016)

Probability of PCa RFS and PCSM for ERβ2 staining quantified by image analysis. Kaplan-Meier plot for PCa recurrence-free survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (a), tumor nuclei (c), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (e). Kaplan-Meier plot for PCa-specific survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (b), tumor nuclei (d), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (f)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940862&req=5

Fig4: Probability of PCa RFS and PCSM for ERβ2 staining quantified by image analysis. Kaplan-Meier plot for PCa recurrence-free survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (a), tumor nuclei (c), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (e). Kaplan-Meier plot for PCa-specific survival using tertiles of ERβ2 intensity quantified by the Cytoplasm algorithm (Aperio) confined to tumor cytoplasm (b), tumor nuclei (d), or by the Color Deconvolution algorithm (Aperio) for area-based quantification confined to tumor cells including cytoplasm and nuclear staining (f)
Mentions: Kaplan-Meier analysis demonstrated that ERβ2 quantified by total malignant epithelial area image analysis was borderline associated with time to recurrence in univariate analysis (p = 0.057; Table 4 and Fig. 4). ERβ2 quantified separately by cytoplasmic image analysis and nuclear image analysis were not significantly associated with time to recurrence in univariate or multivariate analysis (adjusted for clinicopathologic features including age at diagnosis, Gleason score, pathologic stage, and diagnostic PSA level; Table 4 and Fig. 4).Table 4

Bottom Line: Two independent analysis runs were performed to evaluate reproducibility.For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99).After adjusting for clinicopathologic factors, only total malignant epithelial area ERβ2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Washington, 908 Jefferson Street, Room 2NJB244, Seattle, WA, 98104, USA.

ABSTRACT

Background: Digital image analysis offers advantages over traditional pathologist visual scoring of immunohistochemistry, although few studies examining the correlation and reproducibility of these methods have been performed in prostate cancer. We evaluated the correlation between digital image analysis (continuous variable data) and pathologist visual scoring (quasi-continuous variable data), reproducibility of each method, and association of digital image analysis methods with outcomes using prostate cancer tissue microarrays (TMAs) stained for estrogen receptor-β2 (ERβ2).

Methods: Prostate cancer TMAs were digitized and evaluated by pathologist visual scoring versus digital image analysis for ERβ2 staining within tumor epithelium. Two independent analysis runs were performed to evaluate reproducibility. Image analysis data were evaluated for associations with recurrence-free survival and disease specific survival following radical prostatectomy.

Results: We observed weak/moderate Spearman correlation between digital image analysis and pathologist visual scores of tumor nuclei (Analysis Run A: 0.42, Analysis Run B: 0.41), and moderate/strong correlation between digital image analysis and pathologist visual scores of tumor cytoplasm (Analysis Run A: 0.70, Analysis Run B: 0.69). For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99). Further, ERβ2 staining was significantly associated with increased risk of prostate cancer-specific mortality (PCSM) when quantified by cytoplasmic digital image analysis (HR 2.16, 95 % CI 1.02-4.57, p = 0.045), nuclear image analysis (HR 2.67, 95 % CI 1.20-5.96, p = 0.016), and total malignant epithelial area analysis (HR 5.10, 95 % CI 1.70-15.34, p = 0.004). After adjusting for clinicopathologic factors, only total malignant epithelial area ERβ2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012).

Conclusions: Digital methods of immunohistochemical quantification are more reproducible than pathologist visual scoring in prostate cancer, suggesting that digital methods are preferable and especially warranted for studies involving large sample sizes.

No MeSH data available.


Related in: MedlinePlus