Pure and mixed invasive micropapillary carcinoma.

<p>Pure invasive micropapillary carcinoma, ×100 original magnification (A); Mixed carcinoma with IMPC (left up area) and invasive ductal carcinoma, not otherwise specified (right low area), ×40 original magnification (B).</p

The correlations between ICC and respective KI67 LI means according to two score methods.

<p>The ICC was relatively low in intermediate Ki67 LI group (11%-30%) compared with low (≤10%) and high (>30%) Ki67 LI groups according to both methods. X axis: means of Ki67 LI according to two score methods; y axis: ICC.</p

Compared with the cumulative disease free survival rate curve of invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma (IDC) (<i>P</i> = .606).

<p>Compared with the cumulative disease free survival rate curve of invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma (IDC) (<i>P</i> = .606).</p

Disease free survival comparison of patients according to the semi-quantitative ER level in the whole group (<i>P</i> = .023) (A), IMPC group (<i>P</i> = .575) (B) and IDC group (<i>P</i> = .025) (C).

<p>Disease free survival comparison of patients according to the semi-quantitative ER level in the whole group (<i>P</i> = .023) (A), IMPC group (<i>P</i> = .575) (B) and IDC group (<i>P</i> = .025) (C).</p

An Interobserver Reproducibility Analysis of Ki67 Visual Assessment in Breast Cancer

<div><p>Background</p><p>Ki67 labeling index (LI) is used as a predictive marker and is associated with prognosis in breast cancer. However, standardised methodologies for measurement are lacking which has limited its application in clinical practice. In this study, we evaluated the interobserver concordance of visual assessment of Ki67 LI in breast cancer.</p><p>Methods</p><p>Ki67- immunostained slides of 160 cases of primary invasive breast cancer were visual assessed by five breast pathologists with two different methods to choose the scoring fields: (1) hot-spot score, (2) average score. Proportions of positive invasive tumor cells at 10 % intervals were scored. The intra-class correlation coefficient (ICC) was used to assess the interobserver reproducibility.</p><p>Results</p><p>(1) A perfect concordance of Ki67 LI was demonstrated according to both score methods (<i>P</i><0.0001). Average score method (ICC, 0.904) demonstrated a better correlation than hot-spot score method (ICC, 0.894). (2) By respective means according to two score methods, all cases were classified into three groups (≤10%, 11%-30% and >30% Ki-67 LI). The concordance was relatively low in intermediate Ki67 LI group compared with low and high Ki67 LI groups. (3) All cases were classified into three groups by paired-difference (d) between means of hot-spot score and average score (d<5, 5≤d<10, d≥10). The consistency was observed to decrease with increasing paired-difference according to both methods.</p><p>Conclusions</p><p>Visual assessment of Ki67 LI at 10 % intervals is a candidate for a standard method in breast cancer clinical practice. Average score and hot-spot score of visual assessment both demonstrated a perfect concordance, and an overall average assessment across the whole section including hot spots may be a better method. Interobserver concordance of intermediate Ki67 LI in which most cutoffs are located for making clinical decisions was relatively low.</p></div

The ICC and 95% CI on Ki67 LI, stratified by paired-difference between means of hot-spot score and average score.

<p>d: paired-difference between means of hot-spot score and average score</p><p>The ICC and 95% CI on Ki67 LI, stratified by paired-difference between means of hot-spot score and average score.</p

Characteristics of patients in defined subgroups.

1<p><b>IDC:</b> invasive ductal carcinoma not otherwise specified;</p>2<p><b>IMPC:</b> invasive micropapillary breast carcinoma;</p>3<p><b>ER:</b> estrogen receptor status;</p>4<p><b>PR:</b> progesterone receptor status;</p>5<p><b>HER2/neu:</b> human epidermal growth factor receptor 2 status;</p>6<p><b>LVI:</b> Lymphovascular invasion.</p><p>Characteristics of patients in defined subgroups.</p

Clinicopathological features of 160 cases of invasive breast cancer.

<p>For ER and PR, nuclear staining in ≥1% of the tumor cells was considered positive.</p><p>For HER2, HER2 protein overexpression (3+) by immunohistochemical staining or HER2 gene amplification by FISH detection was considered positive.</p><p>Clinicopathological features of 160 cases of invasive breast cancer.</p

Positive stain for EMA antigen on the peripheral cell membranes is suggestive of “inside-out” morphology.

<p>Positive stain for EMA antigen on the peripheral cell membranes is suggestive of “inside-out” morphology.</p

A homogenously stained case of Ki67.

<p>High Ki67 LI was diffuse and homogenous across the slide.</p