Inter-Observer Agreement among Pathologists for Semi-Quantitative Hormone Receptor Scoring in Breast Carcinoma
David A Cohen, David J Dabbs, Kristine L Cooper, Milon Amin, Terrell E Jones, Mirka W Jones, Mamatha Chivukula, Giuliana A Trucco, Rohit Bhargava. Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA; University of Pittsburgh Cancer Institute (UPCI) Biostatistics Facility, Pittsburgh, PA
Background: Hormone receptor immunohistochemical (IHC) semi-quantitative score is more useful than mere positive or negative result in predicting benefit from hormonal therapies. The recently released ASCO/CAP guidelines recommend reporting of hormone receptor test results in a semi-quantitative manner. However, there is a dearth of studies evaluating inter-observer agreement for such semi-quantitative scoring methods.
Design: 74 resected invasive breast cancer specimens (previously ER+ on core biopsy) were considered for this study. Hormone receptor testing was performed on 4 microns thick whole slide tissue sections using estrogen receptor (ER) clone SP1 (Ventana) and progesterone receptor clone 1E2 (Ventana). Hormone receptor immunohistochemical semi-quantitation was performed using the modified H-score. The score consists of the sum of the percent of tumor cells staining multiplied by an ordinal value corresponding to the intensity level (0=none, 1=weak, 2=moderate, and 3=strong). The score ranges from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor). In accordance to ASCO/CAP guidelines, an H-score of ≥ 1 was considered a positive result for both ER and PR. Four Pathologists independently scored each slide and recorded the H-scores. Agreement between observers was analyzed via Fleiss kappa statistics on ER and PR categorical scores. Intraclass correlation coefficient (ICC) was used to estimate the inter-observer agreement for ER and PR H-scores on a continuous scale (0-300).
Results: There was 100% agreement for categorical ER results (kappa of 1) and 97% agreement (kappa of 0.823, P <0.001) for categorical PR results. For quantitative H-scores on ER and PR, ICC-agreement (two-way random effects model measuring absolute agreement of values) and ICC-consistency (two-way random effects model measuring consistency of scores) are reported below.
|ICC (Agreement) Est (95% CI)||ICC (Consistent) Est (95% CI)|
|ER||0.85 (0.79, 0.90)||0.86 (0.80, 0.90)|
|PR||0.87 (0.82, 0.92)||0.89 (0.84, 0.92)|