[89] Inter-Observer Agreement among Pathologists for Assessing Ki-67 Labeling Index on Whole Slides and “Hot Spots” in Breast Carcinomas

Milon Amin, David Cohen, David J Dabbs, Kristine L Cooper, Terrell E Jones, Mirka Jones, Giuliana A Trucco, Mamatha Chivukula, Rohit Bhargava. Magee-Womens Hospital of UPMC, Pittsburgh, PA; University of Pittsburgh Cancer Institute, Pittsburgh, PA

Background: Tumor proliferation rate is an important prognostic factor in breast carcinoma. Ki-67 immunohistochemical labeling index (LI) is helpful in determining the tumor rate of proliferation. However, it remains unclear whether the entire tumor should be considered for calculating the LI or the most proliferative regions (so called “hot spots”). Moreover, data on inter-observer agreement for such semi-quantitative scoring methods is limited.
Design: 74 resected ER+ invasive breast cancer specimens were considered for this study. Ki-67 was performed on 4-micron thick tissue sections using clone 30-9 (Ventana). The whole slide Ki-67 LI (WSLI) was estimated as the percentage of positive cells within the entire tumor section. The “hot spot” Ki-67 LI (HSLI) was scored as the percentage of positive cells in the most densely staining region of the slide. Four pathologists independently scored each slide and recorded the WSLI and HSLI. Agreement between observers was analyzed via intraclass correlation coefficient (ICC). Both ICC(A,1) and ICC(C,1) are reported.
Results: The difference between HSLI and WSLI for observers 1, 3, and 4 was between 0-10 percentage points in >80% of cases. Observer 2 scores showed a 0-20 percentage point difference in 73% of cases and a 0-10 percentage point difference in 51% of cases (table 1).

Table 1. Difference Between WSLI and HSLI for 4 Observers

	Correlation coefficient between WSLI and HSLI	Mean difference HSLI minus WSLI (95% CI)
OB1	0.984	8.9 (7.8,10.0)
OB2	0.875	16.3 (13.0,19.6)
OB3	0.945	5.0 (3.7,6.2)
OB4	0.949	8.0 (6.6, 9.4)

OB: Observer; CI: confidence intervals.

The agreement for WSLI and HSLI between 4 observers is shown in table 2.

Table 2. Agreement for WSLI and HSLI Between 4 Observers

	ICC(A,1) [95% CI]	ICC(C,1) [95% CI]
Ki-67 WSLI	0.55 [0.27,0.73]	0.71 [0.62,0.79]
Ki-67 HSLI	0.50 [0.17,0.72]	0.74 [0.66,0.82]

ICC(A,1): two-way random effects model measuring absolute agreement of values; ICC(C,1): two-way random effects model measuring consistency of scores; CI: confidence intervals.


Conclusions: Tumor proliferation in ER+ breast cancers appears fairly homogeneous as the difference between HSLI and WSLI is ≤10 percentage points in most cases. The more variable component of Ki-67 LI appears to be inter-observer variability as some pathologists consistently score higher or lower than others. Image analysis systems that can distinguish invasive from non-invasive cells may help improve Ki-67 scoring.
Category: Breast

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 17, Monday Morning