Abstract P1-01-07: Distribution pattern of Ki67 immunoreactivity in ductal intraepithelial neoplasia (DIN): Correlation with lesion grade and potential utility
Authors: Ozerdem U , Tavassoli FA 
Published: May 2016

INTRODUCTION: Ki67 labeling index has been proposed as an independent predictive and prognostic factor in patients with ductal intraepithelial neoplasia (DIN). Ki-67 labeling index of 14% has been suggested as a useful cut-off for stratifying DIN patients for adjuvant radiotherapy and hormonal therapy. No data is available regarding either the distribution pattern of Ki67 immunoreactivity within the ducts involved by DIN or potential correlation of these patterns with lesion grade. In this study, the pattern of distribution of the nuclei immunoreactive with Ki67 was examined in DIN1C (DCIS, grade 1), DIN2 (DCIS, grade2), and DIN3 (DCIS, grade 3) to determine if distinctive patterns could be identified and if these patterns would correlate with lesion grade.

METHODS: 47 consecutive DIN cases were retrieved from our departmental files. Of these, 5 qualified as DIN1C, 28 as DIN2 and 14 as DIN3. H&E and Ki67 immunostains were evaluated on each case to elucidate the distribution of Ki67 positive proliferating epithelial cells within the ducts. The DIN cases were evaluated and the patterns of distribution recorded for each case as either basal or haphazard within the epithelial proliferation. Statistical analysis was performed using Chi-square test with Graphpad PRISM statistical analysis software.

RESULTS: There was a statistically significant difference between the 3 groups in terms of basal vs haphazard Ki67 immunostaining (Chi –square test, P=0.0001). Basal staining pattern was dominant (100%) among the DIN1c cases, while haphazard staining pattern was the dominant (100%) distribution among the DIN3 cases. One half of the DIN2 cases showed basal staining pattern, while the other half showed a haphazard staining pattern. This feature could be useful in separating DIN lesions into low grade and high grade eliminating grade 2. We also quantified necrosis on a scale of 0 to 2; 0 indicating absence of necrosis and 2 reflecting comedo type necrosis. Necrosis was more common in the ducts with haphazard Ki67 distribution. The extent of necrosis varied significantly between DIN1c, DIN2 and DIN3 (Chi –square test, P&lt;0.0001)

CONCLUSIONS: Two distinct patterns of Ki67 immunoreactivity are seen in DIN lesions; the basal pattern is characteristic of DIN1 (low grade DIN), whereas a haphazard pattern is dominant in DIN3 (high grade DIN). These patterns could be used to divide grade 2 DIN into low grade and high grade. This approach is easier and potentially more reproducible than counting the percentage of Ki67 positive cells. The information could be useful from a prognostic standpoint and may well be predictive of potential response to radiation, hormonal and targeted therapies.

Citation Format: Ozerdem U, Tavassoli FA. Distribution pattern of Ki67 immunoreactivity in ductal intraepithelial neoplasia (DIN): Correlation with lesion grade and potential utility. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-07.