Abstract 28P
Background
This study investigated the Ki67 proliferation index in human high-grade DCIS with respect to the Luminal (Lum) A, LumB HER2ˉ, LumB HER2+, HER2-enriched, and triple-negative (TPN) subtypes. Additionally, we attempted to determine a more reliable Ki67 cutoff value.
Methods
The study included formalin-fixed paraffin-embedded specimens of 357 high-grade DCIS cases diagnosed between 1996-2018. Routine diagnostic immunohistochemical staining was used. DCIS cases were classified as LumA, LumB HER2ˉ, LumB HER2+, HER2-enriched or TPN, according to the 2013 St. Gallen guidelines. Each subtype was sorted into: “pure”: without an invasive component; “w/invasive”: with an invasive component; and “all”: the entire group of the given subtype. The distribution of Ki67 was studied within each subtype. By applying Cohen's kappa coefficient and a 20% cutoff, the interobserver diagnostic agreement between counting by pathologist 1 (CP1) and CP2 on the Ki67 assessment was determined. We looked at the relationship with HER2 (score 3+) and the distribution of low PR (<20%) together with high Ki67 (≥20%) among LumB HER2ˉ, LumB HER2+, HER2-enriched, and TPN subtypes.
Results
In subtypes in which their classification was not dependent on the Ki67 we identified significant differences among the selected groups (p<0.0001). The median Ki67 was significantly higher in cases with invasive components than in those without invasive components; 25 and 19, respectively (p=0.0351). A combination of low PR level and high Ki67 expression was significantly associated with HER2 overexpression (score 3+) (p=0.0107). The interobserver diagnostic agreement for Ki67 between CP1 and CP2 was moderate (ƙ=0.58).
Conclusions
Ki67 was considerably variable in high-grade DCIS. Low PR combined with high Ki67 was associated with HER2-enriched subtype and HER2 overexpression (score 3+). The interobserver agreement was moderate. Our results indicate that the use of a Ki67 cutoff of 20% as defined by the 2013 St. Gallen are probably not entirely reliable for distinguishing luminal subtypes of high-grade DCIS. However, Ki67 may have a role in identifying those DCIS with invasive potential, paving the way for a new clinical decision making for treatment of DCIS in the future.
Legal entity responsible for the study
J. Geilser.
Funding
University of Oslo and Akershus University Hospital, Norway.
Disclosure
All authors have declared no conflicts of interest.